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1
Ottosson, Filip, Louise Brunkwall, Ulrika Ericson, Peter M. Nilsson, Peter Almgren, Céline Fernandez, Olle Melander, and Marju Orho-Melander. "Connection Between BMI-Related Plasma Metabolite Profile and Gut Microbiota." Journal of Clinical Endocrinology & Metabolism 103, no. 4 (February 1, 2018): 1491–501. http://dx.doi.org/10.1210/jc.2017-02114.
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Abstract Context Emerging evidence has related the gut microbiome and circulating metabolites to human obesity. Gut microbiota is responsible for several metabolic functions, and altered plasma metabolome might reflect differences in the gut microbiome. Objective To identify a plasma metabolite profile associated with body mass index (BMI) in a general population and investigate whether such metabolite profile is associated with distinct composition of the gut microbiota. Design Targeted profiling of 48 plasma metabolites was performed in a population of 920 Swedish adults (mean age, 39 years; 53% women) from the ongoing Malmö Offspring Study using targeted liquid chromatography–mass spectrometry. Gut microbiota was analyzed by sequencing the 16S ribosomal RNA gene (V1-V3 region) in fecal samples of 674 study participants. Results BMI was associated with 19 metabolites (P < 0.001 for all), of which glutamate provided the strongest direct association (P = 5.2e-53). By orthogonal partial least squares regression, a metabolite principal component predictive of BMI was constructed (PCBMI). In addition to glutamate, PCBMI was dominated by branched-chain amino acids (BCAAs) and related metabolites. Four gut microbiota genera (Blautia, Dorea, Ruminococcus, and SHA-98) were associated with both BMI and PCBMI (P < 8.0e-4 for all). When simultaneously regressing PCBMI and metabolite-associated gut bacteria against BMI, only PCBMI remained statistically significant. Conclusions We discovered associations between four gut microbiota genera (Blautia, Dorea, Ruminococcus, and SHA-98) and BMI-predictive plasma metabolites, including glutamate and BCAAs. Thus, these metabolites could be mediators between gut microbiota and obesity, pointing to potential future opportunities for targeting the gut microbiota in prevention of obesity.
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Ugrayová, Simona, Peter Švec, Ivan Hric, Sára Šardzíková, Libuša Kubáňová, Adela Penesová, Jaroslava Adamčáková, et al. "Gut Microbiome Suffers from Hematopoietic Stem Cell Transplantation in Childhood and Its Characteristics Are Positively Associated with Intra-Hospital Physical Exercise." Biology 11, no. 5 (May 21, 2022): 785. http://dx.doi.org/10.3390/biology11050785.
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Gut microbiome impairment is a serious side effect of cancer treatment. The aim of this study was to identify the effects of hematopoietic stem cell transplantation (HSCT) treatment on gut microbiota composition in children with acute lymphoblastic leukemia (ALL). Fecal microbiotas were categorized using specific primers targeting the V1–V3 region of 16S rDNA in eligible pediatric ALL patients after HSCT (n = 16) and in healthy controls (Ctrl, n = 13). An intra-hospital exercise program was also organized for child patients during HSCT treatment. Significant differences in gut microbiota composition were observed between ALL HSCT and Ctrl with further negative effects. Plasma C-reactive protein correlated positively with the pathogenic bacteria Enterococcus spp. and negatively with beneficial bacteria Butyriccocus spp. or Akkermansia spp., respectively (rs = 0.511, p = 0.05; rs = −0.541, p = 0.04; rs = −0.738, p = 0.02). Bacterial alpha diversity correlated with the exercise training characteristics. Therefore, specific changes in the microbiota of children were associated with systemic inflammation or the ability to exercise physically during HSCT treatment.
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Murali, Aishwarya, Varun Giri, Hunter James Cameron, Christina Behr, Saskia Sperber, Hennicke Kamp, Tilmann Walk, and Bennard van Ravenzwaay. "Elucidating the Relations between Gut Bacterial Composition and the Plasma and Fecal Metabolomes of Antibiotic Treated Wistar Rats." Microbiology Research 12, no. 1 (March 1, 2021): 82–122. http://dx.doi.org/10.3390/microbiolres12010008.
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The gut microbiome is vital to the health and development of an organism, specifically in determining the host response to a chemical (drug) administration. To understand this, we investigated the effects of six antibiotic (AB) treatments (Streptomycin sulfate, Roxithromycin, Sparfloxacin, Vancomycin, Clindamycin and Lincomycin hydrochloride) and diet restriction (–20%) on the gut microbiota in 28-day oral toxicity studies on Wistar rats. The fecal microbiota was determined using 16S rDNA marker gene sequencing. AB-class specific alterations were observed in the bacterial composition, whereas restriction in diet caused no observable difference. These changes associated well with the changes in the LC–MS/MS- and GC–MS-based metabolome profiles, particularly of feces and to a lesser extent of plasma. Particularly strong and AB-specific metabolic alterations were observed for bile acids in both plasma and feces matrices. Although AB-group-specific plasma metabolome changes were observed, weaker associations between fecal and plasma metabolome suggest a profound barrier between them. Numerous correlations between the bacterial families and the fecal metabolites were established, providing a holistic overview of the gut microbial functionality. Strong correlations were observed between microbiota and bile acids, lipids and fatty acids, amino acids and related metabolites. These microbiome–metabolome correlations promote understanding of the functionality of the microbiome for its host.
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Zhou, Xueqian, Xiaoxun Zhang, Nan Zhao, Liangjun Zhang, Wen Qiu, Chunwei Song, Jin Chai, Shiying Cai, and Wensheng Chen. "Gut Microbiota Deficiency Exacerbates Liver Injury in Bile Duct Ligated Mice via Inflammation and Lipid Metabolism." International Journal of Molecular Sciences 24, no. 4 (February 6, 2023): 3180. http://dx.doi.org/10.3390/ijms24043180.
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Bile components play a critical role in maintaining gut microbiota homeostasis. In cholestasis, bile secretion is impaired, leading to liver injury. However, it remains to be elucidated whether gut microbiota plays a role in cholestatic liver injury. Here, we performed a sham operation and bile duct ligation (BDL) in antibiotic-induced microbiome depleted (AIMD) mice and assessed liver injury and fecal microbiota composition in these mice. Significant reductions in gut microbiota richness and diversity were found in AIMD-sham mice when compared to sham controls. Three-day BDL leads to great elevation of plasma ALT, ALP, total bile acids, and bilirubin where reduced diversity of the gut microbiota was also found. AIMD further aggravated cholestatic liver injury evidenced by significantly higher levels of plasma ALT and ALP, associated with further reduced diversity and increased Gram-negative bacteria in gut microbiota. Further analyses revealed increased levels of LPS in the plasma of AIMD-BDL mice where elevated expression of inflammatory genes and decreased expression of hepatic detoxification enzymes were also found in liver when compared to the BDL group. These findings indicate that gut microbiota plays a critical role in cholestatic liver injury. Maintaining its homeostasis may alleviate liver injury in patients with cholestasis.
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Luo, Zhengzhong, Li Ma, Tao Zhou, Yixin Huang, Liben Zhang, Zhenlong Du, Kang Yong, et al. "Beta-Glucan Alters Gut Microbiota and Plasma Metabolites in Pre-Weaning Dairy Calves." Metabolites 12, no. 8 (July 26, 2022): 687. http://dx.doi.org/10.3390/metabo12080687.
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The present study aims to evaluate the alterations in gut microbiome and plasma metabolites of dairy calves with β-glucan (BG) supplementation. Fourteen healthy newborn dairy calves with similar body weight were randomly divided into control (n = 7) and BG (n = 7) groups. All the calves were fed on the basal diet, while calves in the BG group were supplemented with oat BG on d 8 for 14 days. Serum markers, fecal microbiome, and plasma metabolites at d 21 were analyzed. The calves were weaned on d 60 and weighed. The mean weaning weight of the BG group was 4.29 kg heavier than that of the control group. Compared with the control group, the levels of serum globulin, albumin, and superoxide dismutase were increased in the BG group. Oat BG intake increased the gut microbiota richness and decreased the Firmicutes-to-Bacteroidetes ratio. Changes in serum markers were found to be correlated with the plasma metabolites, including sphingosine, trehalose, and 3-methoxy-4-hydroxyphenylglycol sulfate, and gut microbiota such as Ruminococcaceae_NK4A214, Alistipes, and Bacteroides. Overall, these results suggest that the BG promotes growth and health of pre-weaning dairy calves by affecting the interaction between the host and gut microbiota.
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Kim, Jeon-Kyung, Eun Kyu Lee, Chu Hyun Bae, Soo-Dong Park, Jae-Jung Shim, Jung-Lyoul Lee, Hye Hyun Yoo, and Dong-Hyun Kim. "The Impact of Gut Microbiome on the Pharmacokinetics of Ginsenosides Rd and Rg3 in Mice after Oral Administration of Red Ginseng." American Journal of Chinese Medicine 49, no. 08 (January 2021): 1897–912. http://dx.doi.org/10.1142/s0192415x21500890.
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Ginsenosides of orally administered red ginseng (RG) extracts are metabolized and absorbed into blood. Here, we examined the pharmacokinetic profiles of ginsenosides Rd and Rg3 in mice orally gavaged with RG, then investigated the correlations between these and gut microbiota composition. RG water extract (RGw), RG ethanol extract (RGe), or fermented RGe (fRGe) was orally gavaged in mice. The plasma concentrations of the ginsenosides were determined, and the gut microbiota composition was analyzed. RGe and fRGe-treated mice showed higher plasma concentration levels of ginsenoside Rd compared with RGw-treated mice; particularly, ginsenoside Rd absorbed was substantially high in fRGe-treated mice. Oral administration of RG extracts modified the gut microbiota composition; the modified gut microbiota, such as Peptococcaceae, Rikenellaceae, and Hungateiclostridiaceae, were closely correlated with the absorption of ginsenosides, such as Rd and Rg3. These results suggest that oral administration of RG extracts can modify gut microbiome, which may consequently affect the bioavailability of RG ginsenosides.
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Saji, Naoki, Kenta Murotani, Naoyuki Sato, Tsuyoshi Tsuduki, Takayoshi Hisada, Mitsuru Shinohara, Taiki Sugimoto, Shumpei Niida, Kenji Toba, and Takashi Sakurai. "Relationship Between Plasma Neurofilament Light Chain, Gut Microbiota, and Dementia: A Cross-Sectional Study." Journal of Alzheimer's Disease 86, no. 3 (April 5, 2022): 1323–35. http://dx.doi.org/10.3233/jad-215141.
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Background: Previous studies have demonstrated associations between gut microbiota, microbial metabolites, and cognitive decline. However, relationships between these factors and neurofilament light chain (NfL; a disease-nonspecific biomarker of neural damage) remain controversial. Objective: To evaluate the associations between plasma NfL, gut microbiota, and cognitive function. Methods: We performed a cross-sectional sub-analysis of data from our prospective cohort study that was designed to investigate the relationship between gut microbiota and cognitive function. Patients who visited our memory clinic were enrolled and demographics, dementia-related risk factors, cognitive function, brain imaging, gut microbiomes, and microbial metabolites were assessed. We evaluated the relationships between the gut microbiome, microbial metabolites, and plasma NfL. Moreover, the relationships between plasma NfL and cognitive function were assessed using multivariable logistic regression analyses. Results: We analyzed 128 participants (women: 59%, mean age: 74 years). Participants with high (above the median) plasma NfL concentrations tended to be older, women, and hypertensive and have a history of stroke, chronic kidney disease, and dementia. Plasma NfL was also associated with cerebral small vessel disease. However, plasma NfL levels were not significantly correlated with gut microbial metabolites. Multivariable analyses revealed that a higher plasma NfL concentration was independently associated with the presence of dementia (odds ratio: 9.94, 95% confidence interval: 2.75–48.2, p < 0.001). Conclusion: High plasma NfL concentration was independently associated with the presence of dementia as previously reported. However, plasma NfL levels were not significantly correlated with gut microbial metabolites in this preliminary study.
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Wang, Yang, Yuanchen He, Rui Li, Hui Jiang, Dengshun Tao, Keyan Zhao, Zongtao Yin, Jian Zhang, and Huishan Wang. "Gut Microbiota in Patients with Postoperative Atrial Fibrillation Undergoing Off-Pump Coronary Bypass Graft Surgery." Journal of Clinical Medicine 12, no. 4 (February 13, 2023): 1493. http://dx.doi.org/10.3390/jcm12041493.
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Background: Post-operative atrial fibrillation (POAF) is one of the most common complications of cardiac surgery. However, the underlying mechanism is not well understood. Alterations in the gut microbiota are associated with the development of atrial fibrillation (AF). The aim of this study was to explore the relationship between gut microbiota and POAF. Methods: Fecal samples were collected before surgery from 45 patients who underwent coronary artery bypass grafting with POAF and 90 matched patients without POAF (1:2). 16S rRNA sequencing was used to detect the microbiome profiles of 45 POAF patients and 89 matched patients (one sample in the no-POAF group was deleted owing to low quality after sequencing). Plasma 25-hydroxy vitamin D level was measured by ELISA. Results: Compared to the patients without POAF, gut microbiota composition was remarkably changed in the patients with POAF, with an increase in Lachnospira, Acinetobacter, Veillonella and Aeromonas, and a decrease in Escherichia–Shigella, Klebsiella, Streptococcus, Brevundimonas and Citrobacter. Furthermore, plasma 25-hydroxy vitamin D levels were decreased in POAF patients and negatively correlated with an abundance of Lachnospira. Conclusions: The gut microbiota composition between patients with and without POAF is significantly different, implying that gut microbiota may play a role in the pathogenesis of POAF. Further studies are needed to fully clarify the role of gut microbiota in the initiation of AF.
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Huang, Yueh-Hsiang, Yi-Hong Wu, Hsiang-Yu Tang, Szu-Tah Chen, Chih-Ching Wang, Wan-Jing Ho, Yi-Hsuan Lin, et al. "Gut Microbiota and Bile Acids Mediate the Clinical Benefits of YH1 in Male Patients with Type 2 Diabetes Mellitus: A Pilot Observational Study." Pharmaceutics 14, no. 9 (September 2, 2022): 1857. http://dx.doi.org/10.3390/pharmaceutics14091857.
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Our previous clinical trial showed that a novel concentrated herbal extract formula, YH1 (Rhizoma coptidis and Shen-Ling-Bai-Zhu-San), improved blood glucose and lipid control. This pilot observational study investigated whether YH1 affects microbiota, plasma, and fecal bile acid (BA) compositions in ten untreated male patients with type 2 diabetes (T2D), hyperlipidemia, and a body mass index ≥ 23 kg/m2. Stool and plasma samples were collected for microbiome, BA, and biochemical analyses before and after 4 weeks of YH1 therapy. As previous studies found, the glycated albumin, 2-h postprandial glucose, triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels were significantly improved after YH1 treatment. Gut microbiota revealed an increased abundance of the short-chain fatty acid-producing bacteria Anaerostipes and Escherichia/Shigella. Furthermore, YH1 inhibited specific phylotypes of bile salt hydrolase-expressing bacteria, including Parabacteroides, Bifidobacterium, and Bacteroides caccae. Stool tauro-conjugated BA levels increased after YH1 treatment. Plasma total BAs and 7α-hydroxy-4-cholesten-3-one (C4), a BA synthesis indicator, were elevated. The reduced deconjugation of BAs and increased plasma conjugated BAs, especially tauro-conjugated BAs, led to a decreased glyco- to tauro-conjugated BA ratio and reduced unconjugated secondary BAs. These results suggest that YH1 ameliorates T2D and hyperlipidemia by modulating microbiota constituents that alter fecal and plasma BA compositions and promote liver cholesterol-to-BA conversion and glucose homeostasis.
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Chang, Chih-Jung, Jing Zhang, Yu-Ling Tsai, Chun-Bing Chen, Chun-Wei Lu, Yu-Ping Huo, Huey-Ming Liou, Chao Ji, and Wen-Hung Chung. "Compositional Features of Distinct Microbiota Base on Serum Extracellular Vesicle Metagenomics Analysis in Moderate to Severe Psoriasis Patients." Cells 10, no. 9 (September 8, 2021): 2349. http://dx.doi.org/10.3390/cells10092349.
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The bacterial microbiota in the skin and intestine of patients with psoriasis were different compared with that of healthy individuals. However, the presence of a distinct blood microbiome in patients with psoriasis is yet to be investigated. In this study, we investigated the differences in bacterial communities in plasma-derived extracellular vesicles (EVs) between patients with moderate to severe psoriasis (PSOs) and healthy controls (HCs). The plasma EVs from the PSO (PASI > 10) (n = 20) and HC (n = 8) groups were obtained via a series of centrifugations, and patterns were examined and confirmed using transmission electron microscopy (TEM) and EV-specific markers. The taxonomic composition of the microbiota was determined by using full-length 16S ribosomal RNA gene sequencing. The PSO group had lower bacterial diversity and richness compared with HC group. Principal coordinate analysis (PCoA)-based clustering was used to assess diversity and validated dysbiosis for both groups. Differences at the level of amplicon sequence variant (ASV) were observed, suggesting alterations in specific ASVs according to health conditions. The HC group had higher levels of the phylum Firmicutes and Fusobacteria than in the PSO group. The order Lactobacillales, family Brucellaceae, genera Streptococcus, and species Kingella oralis and Aquabacterium parvum were highly abundant in the HC group compared with the PSO group. Conversely, the order Bacillales and the genera Staphylococcus and Sphihgomonas, as well as Ralstonia insidiosa, were more abundant in the PSO group. We further predicted the microbiota functional capacities, which revealed significant differences between the PSO and HC groups. In addition to previous studies on microbiome changes in the skin and gut, we demonstrated compositional differences in the microbe-derived EVs in the plasma of PSO patients. Plasma EVs could be an indicator for assessing the composition of the microbiome of PSO patients.
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Koopen, Annefleur M., Nicolien C. de Clercq, Moritz V. Warmbrunn, Hilde Herrema, Mark Davids, Pieter F. de Groot, Ruud S. Kootte, et al. "Plasma Metabolites Related to Peripheral and Hepatic Insulin Sensitivity Are Not Directly Linked to Gut Microbiota Composition." Nutrients 12, no. 8 (July 31, 2020): 2308. http://dx.doi.org/10.3390/nu12082308.
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Plasma metabolites affect a range of metabolic functions in humans, including insulin sensitivity (IS). A subset of these plasma metabolites is modified by the gut microbiota. To identify potential microbial–metabolite pathways involved in IS, we investigated the link between plasma metabolites, gut microbiota composition, and IS, using the gold-standard for peripheral and hepatic IS measurement in a group of participants with metabolic syndrome (MetSyn). In a cross-sectional study with 115 MetSyn participants, fasting plasma samples were collected for untargeted metabolomics analysis and fecal samples for 16S rRNA gene amplicon sequencing. A two-step hyperinsulinemic euglycemic clamp was performed to assess peripheral and hepatic IS. Collected data were integrated and potential interdependence between metabolites, gut microbiota, and IS was analyzed using machine learning prediction models. Plasma metabolites explained 13.2% and 16.7% of variance in peripheral and hepatic IS, respectively. Fecal microbiota composition explained 4.2% of variance in peripheral IS and was not related to hepatic IS. Although metabolites could partially explain the variances in IS, the top metabolites related to peripheral and hepatic IS did not significantly correlate with gut microbiota composition (both on taxonomical level and alpha-diversity). However, all plasma metabolites could explain 18.5% of the variance in microbial alpha-diversity (Shannon); the top 20 metabolites could even explain 44.5% of gut microbial alpha-diversity. In conclusion, plasma metabolites could partially explain the variance in peripheral and hepatic IS; however, these metabolites were not directly linked to the gut microbiota composition, underscoring the intricate relation between plasma metabolites, the gut microbiota, and IS in MetSyn
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Jiang, Huijuan, Xiaoyu Zhao, Mengtong Zang, Rong Fu, Zonghong Shao, and Chunyan Liu. "Gut Microbiome and Plasma Metabolomic Analysis in Patients with Myelodysplastic Syndrome." Oxidative Medicine and Cellular Longevity 2022 (May 9, 2022): 1–21. http://dx.doi.org/10.1155/2022/1482811.
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Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic stem cell disorders. Studies have shown the involvement of an abnormal immune system in MDS pathogenesis. The gut microbiota are known to influence host immunity and metabolism, thereby contributing to the development of hematopoietic diseases. In this study, we performed gut microbiome and plasma metabolomic analyses in patients with MDS and healthy controls. We found that patients with MDS had a different gut microbial composition compared to controls. The gut microbiota in MDS patients showed a continuous evolutionary relationship from the phylum to the species level. At the species level, the abundance of Haemophilus parainfluenzae, Streptococcus luteciae, Clostridium citroniae, and Gemmiger formicilis increased, while that of Prevotella copri decreased in MDS patients compared to controls. Moreover, abundance of bacterial genera correlated with the percentage of lymphocyte subsets in patients with MDS. Metabolomic analysis showed that the concentrations of hypoxanthine and pyroglutamic acid were increased, while that of 3a,7a-dihydroxy-5b-cholestan was decreased in MDS patients compared to controls. In conclusion, gut microbiome and plasma metabolomics are altered in patients with MDS, which may be involved in the immunopathogenesis of the disease.
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Asensio, Eva M., Carolina Ortega-Azorín, Rocío Barragán, Andrea Alvarez-Sala, José V. Sorlí, Eva C. Pascual, Rebeca Fernández-Carrión, Laura V. Villamil, Dolores Corella, and Oscar Coltell. "Association between Microbiome-Related Human Genetic Variants and Fasting Plasma Glucose in a High-Cardiovascular-Risk Mediterranean Population." Medicina 58, no. 9 (September 7, 2022): 1238. http://dx.doi.org/10.3390/medicina58091238.
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Background and Objectives: The gut microbiota has been increasingly recognized as a relevant factor associated with metabolic diseases. However, directly measuring the microbiota composition is a limiting factor for several studies. Therefore, using genetic variables as proxies for the microbiota composition is an important issue. Landmark microbiome–host genome-wide association studies (mbGWAS) have identified many SNPs associated with gut microbiota. Our aim was to analyze the association between relevant microbiome-related genetic variants (Mi-RSNPs) and fasting glucose and type 2 diabetes in a Mediterranean population, exploring the interaction with Mediterranean diet adherence. Materials and Methods: We performed a cross-sectional study in a high-cardiovascular-risk Mediterranean population (n = 1020), analyzing the association of Mi-RSNPs (from four published mbGWAS) with fasting glucose and type 2 diabetes. A single-variant approach was used for fitting fasting glucose and type 2 diabetes to a multivariable regression model. In addition, a Mendelian randomization analysis with multiple variants was performed as a sub-study. Results: We obtained several associations between Mi-RSNPs and fasting plasma glucose involving gut Gammaproteobacteria_HB, the order Rhizobiales, the genus Rumminococcus torques group, and the genus Tyzzerella as the top ranked. For type 2 diabetes, we also detected significant associations with Mi-RSNPs related to the order Rhizobiales, the family Desulfovibrionaceae, and the genus Romboutsia. In addition, some Mi-RSNPs and adherence to Mediterranean diet interactions were detected. Lastly, the formal Mendelian randomization analysis suggested combined effects. Conclusions: Although the use of Mi-RSNPs as proxies of the microbiome is still in its infancy, and although this is the first study analyzing such associations with fasting plasma glucose and type 2 diabetes in a Mediterranean population, some interesting associations, as well as modulations, with adherence to the Mediterranean diet were detected in these high-cardiovascular-risk subjects, eliciting new hypotheses.
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Ed Nignpense, Borkwei, Nidhish Francis, Christopher Blanchard, and Abishek Bommannan Santhakumar. "Bioaccessibility and Bioactivity of Cereal Polyphenols: A Review." Foods 10, no. 7 (July 9, 2021): 1595. http://dx.doi.org/10.3390/foods10071595.
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Cereal bioactive compounds, especially polyphenols, are known to possess a wide range of disease preventive properties that are attributed to their antioxidant and anti-inflammatory activity. However, due to their low plasma concentrations after oral intake, there is controversy regarding their therapeutic benefits in vivo. Within the gastrointestinal tract, some cereal polyphenols are absorbed in the small intestine, with the majority accumulating and metabolised by the colonic microbiota. Chemical and enzymatic processes occurring during gastrointestinal digestion modulate the bioactivity and bioaccessibility of phenolic compounds. The interactions between the cereal polyphenols and the intestinal epithelium allow the modulation of intestinal barrier function through antioxidant, anti-inflammatory activity and mucin production thereby improving intestinal health. The intestinal microbiota is believed to have a reciprocal interaction with polyphenols, wherein the microbiome produces bioactive and bioaccessible phenolic metabolites and the phenolic compound, in turn, modifies the microbiome composition favourably. Thus, the microbiome presents a key link between polyphenol consumption and the health benefits observed in metabolic conditions in numerous studies. This review will explore the therapeutic value of cereal polyphenols in conjunction with their bioaccessibility, impact on intestinal barrier function and interaction with the microbiome coupled with plasma anti-inflammatory effects.
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de Groot, Pieter, Tanja Nikolic, Silvia Pellegrini, Valeria Sordi, Sultan Imangaliyev, Elena Rampanelli, Nordin Hanssen, et al. "Faecal microbiota transplantation halts progression of human new-onset type 1 diabetes in a randomised controlled trial." Gut 70, no. 1 (October 26, 2020): 92–105. http://dx.doi.org/10.1136/gutjnl-2020-322630.
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ObjectiveType 1 diabetes (T1D) is characterised by islet autoimmunity and beta cell destruction. A gut microbiota–immunological interplay is involved in the pathophysiology of T1D. We studied microbiota-mediated effects on disease progression in patients with type 1 diabetes using faecal microbiota transplantation (FMT).DesignPatients with recent-onset (<6 weeks) T1D (18–30 years of age) were randomised into two groups to receive three autologous or allogenic (healthy donor) FMTs over a period of 4 months. Our primary endpoint was preservation of stimulated C peptide release assessed by mixed-meal tests during 12 months. Secondary outcome parameters were changes in glycaemic control, fasting plasma metabolites, T cell autoimmunity, small intestinal gene expression profile and intestinal microbiota composition.ResultsStimulated C peptide levels were significantly preserved in the autologous FMT group (n=10 subjects) compared with healthy donor FMT group (n=10 subjects) at 12 months. Small intestinal Prevotella was inversely related to residual beta cell function (r=−0.55, p=0.02), whereas plasma metabolites 1-arachidonoyl-GPC and 1-myristoyl-2-arachidonoyl-GPC levels linearly correlated with residual beta cell preservation (rho=0.56, p=0.01 and rho=0.46, p=0.042, respectively). Finally, baseline CD4 +CXCR3+T cell counts, levels of small intestinal Desulfovibrio piger and CCL22 and CCL5 gene expression in duodenal biopsies predicted preserved beta cell function following FMT irrespective of donor characteristics.ConclusionFMT halts decline in endogenous insulin production in recently diagnosed patients with T1D in 12 months after disease onset. Several microbiota-derived plasma metabolites and bacterial strains were linked to preserved residual beta cell function. This study provides insight into the role of the intestinal gut microbiome in T1D.Trial registration numberNTR3697.
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Wu, Weida, Li Zhang, Bing Xia, Shanlong Tang, Lei Liu, Jingjing Xie, and Hongfu Zhang. "Bioregional Alterations in Gut Microbiome Contribute to the Plasma Metabolomic Changes in Pigs Fed with Inulin." Microorganisms 8, no. 1 (January 13, 2020): 111. http://dx.doi.org/10.3390/microorganisms8010111.
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Inulin (INU) is a non-digestible carbohydrate, known for its beneficial properties in metabolic disorders. However, whether and how gut microbiota in its regulation contributes to host metabolism has yet to be investigated. We conduct this study to examine the possible associations between the gut microbiota and circulating gut microbiota–host co-metabolites induced by inulin interventions. Plasma and intestinal site samples were collected from the pigs that have consumed inulin diet for 60 days. High-throughput sequencing was adopted for microbial composition, and the GC-TOF-MS-based metabolomics were used to characterize featured plasma metabolites upon inulin intervention. Integrated multi-omics analyses were carried out to establish microbiota–host interaction. Inulin consumption decreased the total cholesterol (p = 0.04) and glucose (p = 0.03) level in serum. Greater β-diversity was observed in the cecum and colon of inulin-fed versus that of control-fed pigs (p < 0.05). No differences were observed in the ileum. In the cecum, 18 genera were altered by inulin, followed by 17 in the colon and 6 in the ileum. Inulin increased propionate, and isobutyrate concentrations but decreased the ratio of acetate to propionate in the cecum, and increased total short fatty acids, valerate, and isobutyrate concentrations in the colon. Metabolomic analysis reveals that indole-3-propionic acid (IPA) was significantly higher, and the branched-chain amino acids (BCAA), L-valine, L-isoleucine, and L-leucine are significantly lower in the inulin groups. Mantel test and integrative analysis revealed associations between plasma metabolites (e.g., IPA, BCAA, L-tryptophan) and inulin-responsive cecal microbial genera. These results indicate that the inulin has regional effects on the intestine microbiome in pigs, with the most pronounced effects occurring in the cecum. Moreover, cecum microbiota plays a pivotal role in the modulation of circulating host metabolites upon inulin intervention
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Zemanová, Nina, Kateřina Lněničková, Markéta Vavrečková, Eva Anzenbacherová, Pavel Anzenbacher, Iveta Zapletalová, Petra Hermanová, Tomáš Hudcovic, Hana Kozáková, and Lenka Jourová. "Gut microbiome affects the metabolism of metronidazole in mice through regulation of hepatic cytochromes P450 expression." PLOS ONE 16, no. 11 (November 9, 2021): e0259643. http://dx.doi.org/10.1371/journal.pone.0259643.
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Microbiome is now considered as a significant metabolic organ with an immense potential to influence overall human health. A number of diseases that are associated with pharmacotherapy interventions was linked with altered gut microbiota. Moreover, it has been reported earlier that gut microbiome modulates the fate of more than 30 commonly used drugs and, vice versa, drugs have been shown to affect the composition of the gut microbiome. The molecular mechanisms of this mutual relationship, however, remain mostly elusive. Recent studies indicate an indirect effect of the gut microbiome through its metabolites on the expression of biotransformation enzymes in the liver. The aim of this study was to analyse the effect of gut microbiome on the fate of metronidazole in the mice through modulation of system of drug metabolizing enzymes, namely by alteration of the expression and activity of selected cytochromes P450 (CYPs). To assess the influence of gut microbiome, germ-free mice (GF) in comparison to control specific-pathogen-free (SPF) mice were used. First, it has been found that the absence of microbiota significantly affected plasma concentration of metronidazole, resulting in higher levels (by 30%) of the parent drug in murine plasma of GF mice. Further, the significant interaction between presence/absence of the gut microbiome and effect of metronidazole application, which together influence mRNA expression of CAR, PPARα, Cyp2b10 and Cyp2c38 was determined. Administration of metronidazole itself influenced significantly mRNA expression of Cyp1a2, Cyp2b10, Cyp2c38 and Cyp2d22. Finally, GF mice have shown lower level of enzyme activity of CYP2A and CYP3A than their SPF counterparts. The results hence have shown that, beside direct bacterial metabolism, different expression and enzyme activity of hepatic CYPs in the presence/absence of gut microbiota may be responsible for the altered metronidazole metabolism.
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Maia, Manuel C., Valeriy Poroyko, Haejung Won, Lorena Almeida, Paulo Gustavo Bergerot, Nazli Dizman, Joann Hsu, Jeremy Jones, Ravi Salgia, and Sumanta K. Pal. "Association of microbiome and plasma cytokine dynamics to nivolumab response in metastatic renal cell carcinoma (mRCC)." Journal of Clinical Oncology 36, no. 6_suppl (February 20, 2018): 656. http://dx.doi.org/10.1200/jco.2018.36.6_suppl.656.
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656 Background: Checkpoint inhibitors (CPI) represent a standard of care in mRCC. The relationship of the microbiome to benefit from CPIs has been suggested in clinical studies in melanoma (Wargo et al ASCO 2017). Here we provide updated evidence of association between microbiome composition, plasma cytokines and response to nivolumab in mRCC patients (pts). Methods: Stool and blood samples were prospectively collected from pts with mRCC at 3 time points relative to nivolumab treatment (baseline, week 4 and week 12) and used to assess gut microbiota composition in two different groups: responders (R; including complete/partial response and stable disease) and non-responders (P; primary progression). For stool analyses, microbial DNA was extracted, 16s rRNA gene tags (v4) were generated by PCR amplification and sequenced using MiSeq (Illumina). Sequence reads were processed by Mothur software, assembled in OTUs, taxonomically annotated and used to construct dissimilarity matrices. Differentially abundant taxa were determined by METASTATS and compared between R and P. We further interrogated whether plasma cytokine profile was influenced by specific bacterial species. Results: Of 20 pts, 16 were evaluable for response. In preliminary analyses, 25,304 OTUs were attributed to 165 genera from 8 phyla. PCoA analysis reveals that the first two principal coordinates can explain 49.2% of data set variation. Subsequent k-means clustering shows an almost complete separation of microbiota in R and P groups (p = 0.07). The analysis of microbiota membership in P and R groups revealed 2 differentially abundant taxonomic units present above 1% abundance. Namely, Roseburia spp and Faecalibacterium spp were significantly elevated in R as compared to P (p < 0.05). Correlations between these bacteria and plasma cytokines will be presented at the meeting. Conclusions: Our results are the first to associate specific microbial genera to nivolumab response in mRCC, and this represents the first effort to combine analysis of the microbiome and serum cytokines. Manipulation of the stool microbiome as a means of modulating nivolumab response should be investigated.
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Wu, Wei-Kai, Chieh-Chang Chen, Po-Yu Liu, Suraphan Panyod, Ben-Yang Liao, Pei-Chen Chen, Hsien-Li Kao, et al. "Identification of TMAO-producer phenotype and host–diet–gut dysbiosis by carnitine challenge test in human and germ-free mice." Gut 68, no. 8 (October 30, 2018): 1439–49. http://dx.doi.org/10.1136/gutjnl-2018-317155.
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ObjectiveThe gut microbiota-derived metabolite, trimethylamine N-oxide (TMAO) plays an important role in cardiovascular disease (CVD). The fasting plasma TMAO was shown as a prognostic indicator of CVD incident in patients and raised the interest of intervention targeting gut microbiota. Here we develop a clinically applicable method called oral carnitine challenge test (OCCT) for TMAO-related therapeutic drug efforts assessment and personalising dietary guidance.DesignA pharmacokinetic study was performed to verify the design of OCCT protocol. The OCCT was conducted in 23 vegetarians and 34 omnivores to validate gut microbiota TMAO production capacity. The OCCT survey was integrated with gut microbiome, host genotypes, dietary records and serum biochemistry. A humanised gnotobiotic mice study was performed for translational validation.ResultsThe OCCT showed better efficacy than fasting plasma TMAO to identify TMAO producer phenotype. The omnivores exhibited a 10-fold higher OR to be high TMAO producer than vegetarians. The TMAO-associated taxa found by OCCT in this study were consistent with previous animal studies. The TMAO producer phenotypes were also reproduced in humanised gnotobiotic mice model. Besides, we found the faecal CntA gene was not associated with TMAO production; therefore, other key relevant microbial genes might be involved. Finally, we demonstrated the urine TMAO exhibited a strong positive correlation with plasma TMAO (r=0.92, p<0.0001) and improved the feasibility of OCCT.ConclusionThe OCCT can be used to identify TMAO-producer phenotype of gut microbiota and may serve as a personal guidance in CVD prevention and treatment.Trial registration numberNCT02838732; Results.
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Chuang, Shih-Te, Chien-Ting Chen, Jui-Chun Hsieh, Kuan-Yi Li, Shang-Tse Ho, and Ming-Ju Chen. "Development of Next-Generation Probiotics by Investigating the Interrelationships between Gastrointestinal Microbiota and Diarrhea in Preruminant Holstein Calves." Animals 12, no. 6 (March 10, 2022): 695. http://dx.doi.org/10.3390/ani12060695.
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(1) Background: We aimed to isolate and identify potential next-generation probiotics (NGP) by investigating the interrelationships between gastrointestinal microbiota and diarrhea in preruminant Holstein calves. (2) Material and methods: Twenty preruminant Holstein calves were divided into healthy and diarrheic groups after the combination outcomes of veterinary diagnosis and fecal scores. The fecal microbiome, plasma cytokines, plasma immunoglobulin (Ig) G and haptoglobin were analyzed. The potential probiotic bacteria were identified by comparing the microbiota difference between healthy and diarrheic calves and correlation analysis with fecal scores and inflammatory markers. The identified bacteria were also isolated for further evaluation for antimicrobial activities and immunoregulatory effects. (3) Results: Microbiota analysis suggested that Ruminococcaceae_UCG_014, Bifidobacterium and Pseudoflavonifractor positively correlated with bovine IgG and negatively correlated with fecal score; inflammatory factors, bovine HP, and IL-8 were classified as beneficial bacteria contributing to the health of the calves. The alternation of gut microbial composition also induced changes in the functional gene enrichment of gut microbiota in calves. The gathering of microbiomic data strongly indicated the possible beneficial effects of Bifidobacterium longum subsp. longum, expected to develop as NGP. After isolation and evaluation of the potential functionality in vitro, two specific bifidobacterial strains demonstrated antimicrobial activities and immunoregulatory effects. (4) Conclusions: The results provide a new probiotic searching approach for preventing gastrointestinal disorders in preruminant calves. Further animal study is necessary to verify the results.
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Dualib, Patricia M., Carla R. Taddei, Gabriel Fernandes, Camila R. S. Carvalho, Luiz Gustavo Sparvoli, Isis T. Silva, Rosiane Mattar, Sandra R. G. Ferreira, Sergio A. Dib, and Bianca de Almeida-Pititto. "Gut Microbiota across Normal Gestation and Gestational Diabetes Mellitus: A Cohort Analysis." Metabolites 12, no. 9 (August 26, 2022): 796. http://dx.doi.org/10.3390/metabo12090796.
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The prevalence of gestational diabetes mellitus (GDM) is a global public health concern. The mechanism that leads to glucose tolerance beyond normal physiological levels to pathogenic conditions remains incompletely understood, and it is speculated that the maternal microbiome may play an important role. This study analyzes the gut microbiota composition in each trimester of weight-matched women with and without GDM and examines possible bacterial genera associations with GDM. This study followed 56 pregnant women with GDM and 59 without admitted to the outpatient clinic during their first/second or third trimester of gestation. They were submitted to a standardized questionnaire, dietary recalls, clinical examination, biological sample collection, and molecular profiling of fecal microbiota. Women with GDM were older and had a higher number of pregnancies than normal-tolerant ones. There was no difference in alpha diversity, and the groups did not differ regarding the overall microbiota structure. A higher abundance of Bacteroides in the GDM group was found. A positive correlation between Christensenellaceae and Intestinobacter abundances with one-hour post-challenge plasma glucose and a negative correlation between Enterococcus and two-hour plasma glucose levels were observed. Bifidobacterium and Peptococcus abundances were increased in the third gestational trimester for both groups. The gut microbiota composition was not dependent on the presence of GDM weight-matched women throughout gestation. However, some genera abundances showed associations with glucose metabolism. Our findings may therefore encourage a deeper understanding of physiological and pathophysiological changes in the microbiota throughout pregnancy, which could have further implications for diseases prevention.
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Shigeno, Yuko, Hong Liu, Chie Sano, Ryo Inoue, Kimie Niimi, and Kentaro Nagaoka. "Individual variations and effects of birth facilities on the fecal microbiome of laboratory-bred marmosets (Callithrix jacchus) assessed by a longitudinal study." PLOS ONE 17, no. 8 (August 30, 2022): e0273702. http://dx.doi.org/10.1371/journal.pone.0273702.
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Laboratory animals are used for scientific research in various fields. In recent years, there has been a concern that the gut microbiota may differ among laboratory animals, which may yield different results in different laboratories where in-vivo experiments are performed. Our knowledge of the gut microbiota of laboratory-reared common marmosets (Callithrix jacchus) is limited; thus, in this study, we analyzed the daily changes in fecal microbiome composition, individual variations, and effects of the birth facility in healthy female laboratory-reared marmosets, supplied by three vendors. We showed that the marmoset fecal microbiome varied among animals from the same vendor and among animals from different vendors (birth facility), with daily changes of approximately 37%. The fecal microbiome per vendor is characterized by alpha diversity and specific bacteria, with Bifidobacterium for vendor A, Phascolarctobacterium for vendor B, and Megamonas for vendor C. Furthermore, we found that plasma progesterone concentrations and estrous cycles were not correlated with daily fecal microbiome changes. In contrast, animals with an anovulatory cycle lacked Megamonas and Desulfovibrio bacteria compared to normal estrous females. This study suggests that the source of the animal, such as breeding and housing facilities, is important for in-vivo experiments on the marmoset gut microbiota.
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Rossi, Tania, Daniele Vergara, Francesca Fanini, Michele Maffia, Sara Bravaccini, and Francesca Pirini. "Microbiota-Derived Metabolites in Tumor Progression and Metastasis." International Journal of Molecular Sciences 21, no. 16 (August 12, 2020): 5786. http://dx.doi.org/10.3390/ijms21165786.
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Microbial communities and human cells, through a dynamic crosstalk, maintain a mutualistic relationship that contributes to the maintenance of cellular metabolism and of the immune and neuronal systems. This dialogue normally occurs through the production and regulation of hormonal intermediates, metabolites, secondary metabolites, proteins, and toxins. When the balance between host and microbiota is compromised, the dynamics of this relationship change, creating favorable conditions for the development of diseases, including cancers. Microbiome metabolites can be important modulators of the tumor microenvironment contributing to regulate inflammation, proliferation, and cell death, in either a positive or negative way. Recent studies also highlight the involvement of microbiota metabolites in inducing epithelial–mesenchymal transition, thus favoring the setup of the metastatic niche. An investigation of microbe-derived metabolites in “liquid” human samples, such as plasma, serum, and urine, provide further information to clarify the relationship between host and microbiota.
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Nakai, Michael, Rosilene V. Ribeiro, Bruce R. Stevens, Paul Gill, Rikeish R. Muralitharan, Stephanie Yiallourou, Jane Muir, et al. "Essential Hypertension Is Associated With Changes in Gut Microbial Metabolic Pathways: A Multisite Analysis of Ambulatory Blood Pressure." Hypertension 78, no. 3 (September 2021): 804–15. http://dx.doi.org/10.1161/hypertensionaha.121.17288.
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Recent evidence supports a role for the gut microbiota in hypertension, but whether ambulatory blood pressure is associated with gut microbiota and their metabolites remains unclear. We characterized the function of the gut microbiota, their metabolites and receptors in untreated human hypertensive participants in Australian metropolitan and regional areas. Ambulatory blood pressure, fecal microbiome predicted from 16S rRNA gene sequencing, plasma and fecal metabolites called short-chain fatty acid, and expression of their receptors were analyzed in 70 untreated and otherwise healthy participants from metropolitan and regional communities. Most normotensives were female (66%) compared with hypertensives (35%, P <0.01), but there was no difference in age between the groups (59.2±7.7 versus 60.3±6.6 years old). Based on machine learning multivariate covariance analyses of de-noised amplicon sequence variant prevalence data, we determined that there were no significant differences in predicted gut microbiome α- and β-diversity metrics between normotensives versus essential or masked hypertensives. However, select taxa were specific to these groups, notably Acidaminococcus spp ., Eubacterium fissicatena, and Muribaculaceae were higher, while Ruminococcus and Eubacterium eligens were lower in hypertensives. Importantly, normotensive and essential hypertensive cohorts could be differentiated based on gut microbiome gene pathways and metabolites. Specifically, hypertensive participants exhibited higher plasma acetate and butyrate, but their immune cells expressed reduced levels of short-chain fatty acid-activated GPR43 (G-protein coupled receptor 43). In conclusion, gut microbial diversity did not change in essential hypertension, but we observed a significant shift in microbial gene pathways. Hypertensive subjects had lower levels of GPR43, putatively blunting their response to blood pressure-lowering metabolites.
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Jones, Emily, Régis Stentz, Andrea Telatin, George M. Savva, Catherine Booth, David Baker, Steven Rudder, Stella C. Knight, Alistair Noble, and Simon R. Carding. "The Origin of Plasma-Derived Bacterial Extracellular Vesicles in Healthy Individuals and Patients with Inflammatory Bowel Disease: A Pilot Study." Genes 12, no. 10 (October 18, 2021): 1636. http://dx.doi.org/10.3390/genes12101636.
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The gastrointestinal tract harbors the gut microbiota, structural alterations of which (dysbiosis) are linked with an increase in gut permeability (“leaky gut”), enabling luminal antigens and bacterial products such as nanosized bacterial extracellular vesicles (BEVs) to access the circulatory system. Blood-derived BEVs contain various cargoes and may be useful biomarkers for diagnosis and monitoring of disease status and relapse in conditions such as inflammatory bowel disease (IBD). To progress this concept, we developed a rapid, cost-effective protocol to isolate BEV-associated DNA and used 16S rRNA gene sequencing to identify bacterial origins of the blood microbiome of healthy individuals and patients with Crohn’s disease and ulcerative colitis. The 16S rRNA gene sequencing successfully identified the origin of plasma-derived BEV DNA. The analysis showed that the blood microbiota richness, diversity, or composition in IBD, healthy control, and protocol control groups were not significantly distinct, highlighting the issue of ‘kit-ome’ contamination in low-biomass studies. Our pilot study provides the basis for undertaking larger studies to determine the potential use of blood microbiota profiling as a diagnostic aid in IBD.
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Hsu, Chien-Ning, Chih-Yao Hou, Guo-Ping Chang-Chien, Sufan Lin, Hung-Wei Yang, and You-Lin Tain. "Perinatal Resveratrol Therapy Prevents Hypertension Programmed by Maternal Chronic Kidney Disease in Adult Male Offspring: Implications of the Gut Microbiome and Their Metabolites." Biomedicines 8, no. 12 (December 4, 2020): 567. http://dx.doi.org/10.3390/biomedicines8120567.
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The gut microbiota plays a critical role in kidney disease and hypertension; however, whether maternal chronic kidney disease (CKD)-induced offspring hypertension is associated with alterations of the microbiota and microbial metabolites remains elusive. Using rat as an animal model, we conducted a maternal adenine-induced CKD model to examine whether adult male offspring develop hypertension and kidney disease. As resveratrol has antioxidant and prebiotic properties, we also aimed to elucidate whether its use in pregnancy and lactation can benefit hypertension programmed by maternal CKD via mediation of the gut microbiota and oxidative stress. Female Sprague-Dawley rats received regular chow (C) or chow supplemented with 0.5% adenine (CKD) from 3 weeks before pregnancy until lactation. One group of the adenine-induced CKD pregnant rats received resveratrol (R; 50 mg/L) in drinking water during gestation and lactation. Male offspring were divided into three groups: C, CKD, and CKD+R. The microbial metabolites analyzed were short chain fatty acids (SCFAs) in feces and trimethylamine (TMA)/trimethylamine N-oxide (TMAO) in plasma. We found perinatal resveratrol therapy protected against maternal CKD-induced hypertension in adult male offspring. The overall microbial compositions and diversity of bacterial community in the three groups were different. Resveratrol therapy increased α-diversity, decreased the Firmicutes to Bacteroidetes ratio, and increased the abundance of the genera Lactobacillus and Bifidobacterium. Perinatal resveratrol therapy increased plasma TMA levels but decreased the plasma TMAO-to-TMA ratio. Although resveratrol had negligible effect on fecal concentrations of SCFAs, it increased G-protein coupled receptor-41 (GPR41) protein levels in the offspring’s kidneys. Additionally, resveratrol therapy increased plasma levels of L-arginine and the L-arginine-to-ADMA ratio (AAR), and decreased oxidative stress. Overall, the protective effects of resveratrol against programmed hypertension are related to gut microbiome remodeling, including an increased abundance of beneficial microbes, mediation of the TMA-TMAO pathway, and alterations of SCFA receptors. Our results highlighted that targeting the microbiome and their metabolites might be potential therapeutic strategies to prevent maternal CKD-induced adverse pregnancy and offspring outcomes.
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Reinhardt, Christoph. "The Gut Microbiota as an Influencing Factor of Arterial Thrombosis." Hämostaseologie 39, no. 02 (November 20, 2018): 173–79. http://dx.doi.org/10.1055/s-0038-1675357.
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AbstractThe mutualistic gut microbiota does not only impact the development and function of various immune cell types, but it also influences the function of the hepatic vascular endothelium and prothrombotic platelet function. With germ-free mouse models, we have demonstrated that gut-derived microbial-associated molecular patterns could stimulate hepatic von Willebrand factor (VWF) synthesis and plasmatic VWF levels through Toll-like receptor-2 (TLR2), thus defining the extent of platelet deposition to the subendothelial matrix of the ligation-injured common carotid artery. In addition to the microbiota-derived choline metabolite trimethylamine N-oxide and the microbiota's regulatory role on the colonic serotonin biosynthesis pathway, affecting prothrombotic platelet function, TLR2-regulated hepatic endothelial VWF synthesis and elevated VWF plasma levels constitute a pivotal mechanism of how the gut microbiota is linked to arterial thrombosis. Conceptually, in addition to the identified functions of the gut microbiota in modulating host nutrition and metabolism, our work places the innate immune functions of the liver sinusoidal endothelium as an actuating variable in arterial thrombus growth.
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Park, Jinkyeong, Jae Jun Lee, Yoonki Hong, Hochan Seo, Tae-Seop Shin, and Ji Young Hong. "Metagenomic Analysis of Plasma Microbial Extracellular Vesicles in Patients Receiving Mechanical Ventilation: A Pilot Study." Journal of Personalized Medicine 12, no. 4 (April 2, 2022): 564. http://dx.doi.org/10.3390/jpm12040564.
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Background: Previous studies reported a significant association between pneumonia outcome and the respiratory microbiome. There is increasing interest in the roles of bacterial extracellular vesicles (EVs) in various diseases. We studied the composition and function of microbiota-derived EVs in the plasma of patients receiving mechanical ventilation to evaluate whether they can be used as a diagnostic marker and to predict clinical outcomes. Methods: Plasma samples (n = 111) from 59 mechanically ventilated patients (41 in the pneumonia group; 24 in the nursing home and hospital-associated infection [NHAI] group) were prospectively collected on days one and seven. After isolating the bacterial EVs from plasma samples, nucleic acid was extracted for 16S rRNA gene pyrosequencing. The samples were evaluated to determine the α and β diversity, bacterial composition, and predicted functions. Results: Principal coordinates analysis revealed significantly different clustering of microbial EVs between the pneumonia and non-pneumonia groups. The proportions of Lactobacillus, Cutibacterium, and Sphingomonas were significantly different between the pneumonia and non-pneumonia groups. In addition, the abundances of Lactobacillus and Bifidobacterium were significantly higher in the non-NHAI than the NHAI group. In the analysis of β diversity, the structure of microbial EVs differed significantly different between 28-day survivors and non-survivors (Bray-Curtis distance, p = 0.014). Functional profiling revealed significant differences between the pneumonia and non-pneumonia groups. The longitudinal change in predicted functions of microbial EV genes showed a significant difference between 28-day survivors and non-survivors. Conclusions: Bacterial microbiota–derived EVs in the plasma have potential as diagnostic and prognostic markers for patients receiving mechanical ventilation. Further large prospective studies are needed to determine the clinical utility of plasma microbiota-EVs in intubated patients.
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Boussamet, Léo, Muhammad Shahid Riaz Rajoka, and Laureline Berthelot. "Microbiota, IgA and Multiple Sclerosis." Microorganisms 10, no. 3 (March 14, 2022): 617. http://dx.doi.org/10.3390/microorganisms10030617.
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Multiple sclerosis (MS) is a neuroinflammatory disease characterized by immune cell infiltration in the central nervous system and destruction of myelin sheaths. Alterations of gut bacteria abundances are present in MS patients. In mouse models of neuroinflammation, depletion of microbiota results in amelioration of symptoms, and gavage with MS patient microbiota exacerbates the disease and inflammation via Th17 cells. On the other hand, depletion of B cells using anti-CD20 is an efficient therapy in MS, and growing evidence shows an important deleterious role of B cells in MS pathology. However, the failure of TACI-Ig treatment in MS highlighted the potential regulatory role of plasma cells. The mechanism was recently demonstrated involving IgA+ plasma cells, specific for gut microbiota and producing IL-10. IgA-coated bacteria in MS patient gut exhibit also modifications. We will focus our review on IgA interactions with gut microbiota and IgA+ B cells in MS. These recent data emphasize new pathways of neuroinflammation regulation in MS.
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Kharlamov, V. A., I. V. Polyakova, and D. I. Petrukhina. "Non-thermal argon plasma biocidal effect on the barley seed microbiota." Machinery and Equipment for Rural Area, no. 4 (April 27, 2021): 20–23. http://dx.doi.org/10.33267/2072-9642-2021-4-20-23.
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The non - thermal argon plasma biocidal effect to be determined by the decrease in the total microbial count (36.7% reduction when barley seeds are treated for 5 minutes) of the surface microbiota has been shown. Microorganisms of the surface microbiota of the studied seeds have been isolated and identified. Plasma treatment is recommended to reduce microbiological contamination of agricultural plant seeds.
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Garcia-Ibañez, Paula, Carles Roses, Agatha Agudelo, Fermin I. Milagro, Ana M. Barceló, Blanca Viadel, Juan Antonio Nieto, Diego A. Moreno, and Micaela Carvajal. "The Influence of Red Cabbage Extract Nanoencapsulated with Brassica Plasma Membrane Vesicles on the Gut Microbiome of Obese Volunteers." Foods 10, no. 5 (May 10, 2021): 1038. http://dx.doi.org/10.3390/foods10051038.
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The aim of the study was to evaluate the influence of the red cabbage extracts on the bioaccessibility of their isothiocyanates, and their effect on the intestinal microbiota using a dynamic model of human digestion treated with the gut microbiome of obese adults. The elicitation of red cabbage plants with methyl jasmonate (MeJA) duplicated the content of glucosinolates (GSLs) in the plant organs used for elaborating the encapsulated formula. The use of plasma membrane vesicles, according to a proper methodology and technology, showed a high retention of sulforaphane (SFN) and indol-3-carbinol (I3C) over the course of the 14-day digestion study. The microbiome was scarcely affected by the treatments in terms of microbiota composition or the Bacteroidetes/Firmicutes ratio, but a 3 to 4-fold increase was observed in the production of butyric acid with the encapsulated extract treatment. Based on our pilot red cabbage extract study, the consumption of this extract, mainly encapsulated, may play a potential role in the management of obesity in adults.
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Burz, Sebastian D., Magali Monnoye, Catherine Philippe, William Farin, Vlad Ratziu, Francesco Strozzi, Jean-Michel Paillarse, Laurent Chêne, Hervé M. Blottière, and Philippe Gérard. "Fecal Microbiota Transplant from Human to Mice Gives Insights into the Role of the Gut Microbiota in Non-Alcoholic Fatty Liver Disease (NAFLD)." Microorganisms 9, no. 1 (January 19, 2021): 199. http://dx.doi.org/10.3390/microorganisms9010199.
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Non-alcoholic fatty liver diseases (NAFLD) are associated with changes in the composition and metabolic activities of the gut microbiota. However, the causal role played by the gut microbiota in individual susceptibility to NAFLD and particularly at its early stage is still unclear. In this context, we transplanted the microbiota from a patient with fatty liver (NAFL) and from a healthy individual to two groups of mice. We first showed that the microbiota composition in recipient mice resembled the microbiota composition of their respective human donor. Following administration of a high-fructose, high-fat diet, mice that received the human NAFL microbiota (NAFLR) gained more weight and had a higher liver triglycerides level and higher plasma LDL cholesterol than mice that received the human healthy microbiota (HR). Metabolomic analyses revealed that it was associated with lower and higher plasma levels of glycine and 3-Indolepropionic acid in NAFLR mice, respectively. Moreover, several bacterial genera and OTUs were identified as differently represented in the NAFLR and HR microbiota and therefore potentially responsible for the different phenotypes observed. Altogether, our results confirm that the gut bacteria play a role in obesity and steatosis development and that targeting the gut microbiota may be a preventive or therapeutic strategy in NAFLD management.
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Pietzner, Maik, Kathrin Budde, Malte Rühlemann, Henry Völzke, Georg Homuth, Frank U. Weiss, Markus M. Lerch, and Fabian Frost. "Exocrine Pancreatic Function Modulates Plasma Metabolites Through Changes in Gut Microbiota Composition." Journal of Clinical Endocrinology & Metabolism 106, no. 5 (January 19, 2021): e2290-e2298. http://dx.doi.org/10.1210/clinem/dgaa961.
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Abstract Purpose Exocrine pancreatic function is critically involved in regulating the gut microbiota composition. At the same time, its impairment acutely affects human metabolism. How these 2 roles are connected is unknown. We studied how the exocrine pancreas contributes to metabolism via modulation of gut microbiota. Design Fecal samples were collected in 2226 participants of the population-based Study of Health in Pomerania (SHIP/SHIP-TREND) to determine exocrine pancreatic function (pancreatic elastase enzyme-linked immunosorbent assay) and intestinal microbiota profiles (16S ribosomal ribonucleic acid gene sequencing). Plasma metabolite levels were determined by mass spectrometry. Results Exocrine pancreatic function was associated with changes in the abundance of 28 taxa and, simultaneously, with those of 16 plasma metabolites. Mediation pathway analysis revealed that a significant component of how exocrine pancreatic function affects the blood metabolome is mediated via gut microbiota abundance changes, most prominently, circulating serotonin and lysophosphatidylcholines. Conclusion These results imply that the effect of exocrine pancreatic function on intestinal microbiota composition alters the availability of microbial-derived metabolites in the blood and thus directly contributes to the host metabolic changes associated with exocrine pancreatic dysfunction.
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Wang, Xin, Xueqi Li, and Yumei Dong. "Vitamin D Decreases Plasma Trimethylamine-N-oxide Level in Mice by Regulating Gut Microbiota." BioMed Research International 2020 (October 5, 2020): 1–11. http://dx.doi.org/10.1155/2020/9896743.
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As a metabolite generated by gut microbiota, trimethylamine-N-oxide (TMAO) has been proven to promote atherosclerosis and is a novel potential risk factor for cardiovascular disease (CVD). The objective of this study was to examine whether regulating gut microbiota by vitamin D supplementation could reduce the plasma TMAO level in mice. For 16 weeks, C57BL/6J mice were fed a chow (C) or high-choline diet (HC) without or with supplementation of vitamin D3 (CD3 and HCD3) or a high-choline diet with vitamin D3 supplementation and antibiotics (HCD3A). The results indicate that the HC group exhibited higher plasma trimethylamine (TMA) and TMAO levels, lower richness of gut microbiota, and significantly increased Firmicutes and decreased Bacteroidetes as compared with group C. Vitamin D supplementation significantly reduced plasma TMA and TMAO levels in mice fed a high-choline diet. Furthermore, gut microbiota composition was regulated, and the Firmicutes/Bacteroidetes ratio was reduced by vitamin D. Spearman correlation analysis indicated that Bacteroides and Akkermansia were negatively correlated with plasma TMAO in the HC and HCD3 groups. Our study provides a novel avenue for the prevention and treatment of CVD with vitamin D.
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Zaidan, Nadim, and Lama Nazzal. "The Microbiome and Uremic Solutes." Toxins 14, no. 4 (March 30, 2022): 245. http://dx.doi.org/10.3390/toxins14040245.
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Uremic retention solutes, especially the protein-bound compounds, are toxic metabolites, difficult to eliminate with progressive renal functional decline. They are of particular interest because these uremic solutes are responsible for the pathogenesis of cardiovascular and chronic kidney diseases. Evidence suggests that the relation between uremic toxins, the microbiome, and its host is altered in patients with chronic kidney disease, with the colon’s motility, epithelial integrity, and absorptive properties also playing an important role. Studies found an alteration of the microbiota composition with differences in species proportion, diversity, and function. Since uremic toxins precursors are generated by the microbiota, multiple therapeutic options are currently being explored to address dysbiosis. While an oral adsorbent can decrease the transport of bacterial metabolites from the intestinal lumen to the blood, dietary measures, supplements (prebiotics, probiotics, and synbiotics), and antibiotics aim to target directly the gut microbiota composition. Innovative approaches, such as the modulation of bacterial enzymes, open new perspectives to decrease the plasma level of uremic toxins.
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Ivashkin, V. T., O. S. Medvedev, E. A. Poluektova, A. V. Kudryavtseva, I. R. Bakhtogarimov, and A. E. Karchevskaya. "Direct and Indirect Methods for Studying Human Gut Microbiota." Russian Journal of Gastroenterology, Hepatology, Coloproctology 32, no. 2 (May 15, 2022): 19–34. http://dx.doi.org/10.22416/1382-4376-2022-32-2-19-34.
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Aim: To review the main methods of intestinal microbiota studying.Key points. Currently, molecular genetic methods are used mainly for basic research and do not have a unified protocol for data analysis, which makes it difficult to implement them in clinical practice. Measurement of short chain fatty acids (SCFA) concentrations in plasma provides the data, which can serve as an indirect biomarker of the colonic microbiota composition. However, currently available evidence is insufficient to relate the obtained values (SCFA levels and ratio) to a particular disease with a high degree of certainty. Trimethylamine N-oxide (TMAO) levels in the blood plasma and urine can also reflect the presence of specific bacterial clusters containing genes Cut, CntA/CntB and YeaW/YeaX. Therefore, further studies are required to reveal possible correlations between certain disorders and such parameters as the composition of gut microbiota, dietary patterns and TMAO concentration. Gas biomarkers, i.e. hydrogen, methane and hydrogen sulphide, have been studied in more detail and are better understood as compared to other biomarkers of the gut microbiome composition and functionality. The main advantage of gas biomarkers is that they can be measured multiple times using non-invasive techniques. These measurements provide information on the relative proportion of hydrogenic (i.e. hydrogen producing) and hydrogenotrophic (i.e. methanogenic and sulfate-reducing) microorganisms. In its turn, this opens up the possibility of developing new approaches to correction of individual microbiota components.Conclusions. Integration of the data obtained by gut microbiota studies at the genome, transcriptome and metabolome levels would allow a comprehensive analysis of microbial community function and its interaction with the human organism. This approach may increase our understanding of the pathogenesis of various diseases as well open up new opportunities for prevention and treatment.
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Karl, J. Philip, Lee M. Margolis, Elisabeth H. Madslien, Nancy E. Murphy, John W. Castellani, Yngvar Gundersen, Allison V. Hoke, et al. "Changes in intestinal microbiota composition and metabolism coincide with increased intestinal permeability in young adults under prolonged physiological stress." American Journal of Physiology-Gastrointestinal and Liver Physiology 312, no. 6 (June 1, 2017): G559—G571. http://dx.doi.org/10.1152/ajpgi.00066.2017.
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The magnitude, temporal dynamics, and physiological effects of intestinal microbiome responses to physiological stress are poorly characterized. This study used a systems biology approach and a multiple-stressor military training environment to determine the effects of physiological stress on intestinal microbiota composition and metabolic activity, as well as intestinal permeability (IP). Soldiers ( n = 73) were provided three rations per day with or without protein- or carbohydrate-based supplements during a 4-day cross-country ski-march (STRESS). IP was measured before and during STRESS. Blood and stool samples were collected before and after STRESS to measure inflammation, stool microbiota, and stool and plasma global metabolite profiles. IP increased 62 ± 57% (mean ± SD, P < 0.001) during STRESS independent of diet group and was associated with increased inflammation. Intestinal microbiota responses were characterized by increased α-diversity and changes in the relative abundance of >50% of identified genera, including increased abundance of less dominant taxa at the expense of more dominant taxa such as Bacteroides. Changes in intestinal microbiota composition were linked to 23% of metabolites that were significantly altered in stool after STRESS. Together, pre-STRESS Actinobacteria relative abundance and changes in serum IL-6 and stool cysteine concentrations accounted for 84% of the variability in the change in IP. Findings demonstrate that a multiple-stressor military training environment induced increases in IP that were associated with alterations in markers of inflammation and with intestinal microbiota composition and metabolism. Associations between IP, the pre-STRESS microbiota, and microbiota metabolites suggest that targeting the intestinal microbiota could provide novel strategies for preserving IP during physiological stress.NEW & NOTEWORTHY Military training, a unique model for studying temporal dynamics of intestinal barrier and intestinal microbiota responses to stress, resulted in increased intestinal permeability concomitant with changes in intestinal microbiota composition and metabolism. Prestress intestinal microbiota composition and changes in fecal concentrations of metabolites linked to the microbiota were associated with increased intestinal permeability. Findings suggest that targeting the intestinal microbiota could provide novel strategies for mitigating increases in intestinal permeability during stress.
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Eve, Alicia Arredondo, Xiaoji Liu, Yanling Wang, Michael J. Miller, Elizabeth H. Jeffery, and Zeynep Madak-Erdogan. "Biomarkers of Broccoli Consumption: Implications for Glutathione Metabolism and Liver Health." Nutrients 12, no. 9 (August 20, 2020): 2514. http://dx.doi.org/10.3390/nu12092514.
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Diet and lifestyle choices contribute to obesity and liver disease. Broccoli, a brassica vegetable, may mitigate negative effects of both diet and lifestyle. Currently, there are no clinically relevant, established molecular biomarkers that reflect variability in human absorption of brassica bioactives, which may be the cause of variability/inconsistencies in health benefits in the human population. Here, we focused on the plasma metabolite profile and composition of the gut microbiome in rats, a relatively homogenous population in terms of gut microbiota, genetics, sex and diet, to determine if changes in the plasma metabolite profiles caused by dietary broccoli relate to molecular changes in liver. Our aim was to identify plasma indicators that reflect how liver health is impacted by dietary broccoli. Rats were fed a 10% broccoli diet for 14 days. We examined the plasma metabolite composition by metabolomics analysis using GC–MS and gut microbiota using 16S sequencing after 0, 1, 2, 4, 7, 14 days of broccoli feeding. We identified 25 plasma metabolites that changed with broccoli consumption, including metabolites associated with hepatic glutathione synthesis, and with de novo fatty acid synthesis. Glutamine, stearic acid, and S-methyl-L-cysteine (SMC) relative abundance changes correlated with changes in gut bacteria previously implicated in metabolic disease and with validated increases in expression of hepatic NAD(P)H dehydrogenase [quinone] 1 (NQO1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2), associated with elevated hepatic glutathione synthesis. Circulating biomarkers following broccoli consumption reflect gut–liver axis health.
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Ahn, In-Sook, Justin Yoon, Graciel Diamante, Peter Cohn, Cholsoon Jang, and Xia Yang. "Disparate Metabolomic Responses to Fructose Consumption between Different Mouse Strains and the Role of Gut Microbiota." Metabolites 11, no. 6 (May 26, 2021): 342. http://dx.doi.org/10.3390/metabo11060342.
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High fructose consumption has been linked to metabolic syndrome, yet the fructose-induced phenotypes, gene expression, and gut microbiota alterations are distinct between mouse strains. In this study, we aim to investigate how fructose consumption shapes the metabolomic profiles of mice with different genetic background and microbiome. We used fructose-sensitive DBA/2J (DBA) and fructose-resistant C57BL/6J (B6) mice given 8% fructose or regular water for 12 weeks. Plasma and fecal metabolites were profiled using a liquid chromatography-tandem mass spectrometry based global metabolomic approach. We found that the baseline metabolomic profiles were different between DBA and B6 mice, particularly plasma metabolites involved in lipid metabolism and fecal metabolites related to dipeptide/amino acid metabolism. In response to fructose, DBA mice showed a distinct decrease of plasma branched chain fatty acids with concordantly increased branched chain amino acids, which were correlated with adiposity; B6 mice had significantly increased plasma cholesterol and total bile acids, accompanied by decreased fecal levels of farnesoid X receptor antagonist tauro-β-muricholate, which were correlated with fructose-responsive bacteria Dehalobacterium, Magibacteriaceae, and/or Akkermansia. Our results demonstrate that baseline metabolomic profiles differ and respond differentially to fructose between mice with different genetic background and gut microbiota, which may play a role in individualized risks to fructose-induced metabolic syndrome.
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Cheng, Chuanshang, Hongkui Wei, and Jian Peng. "370 Dietary soluble fiber increases the intestinal butyrate-producing bacteria, reduces intestinal permeability, and improves metabolic syndrome in sows during perinatal period." Journal of Animal Science 97, Supplement_3 (December 2019): 133. http://dx.doi.org/10.1093/jas/skz258.271.
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Abstract In humans, metabolic and immune changes during the perinatal period also describe metabolic syndrome. Gut microbiota can cause symptoms of metabolic syndrome in pregnant women. Gut microbiota modulations caused by pregnancy nutrition constitute an interesting target in the metabolic status of pregnant individual. However, studies investigating the changes of the metabolic characteristics and gut microbiota in sows throughout pregnancy and lactation are lacking, and the effects of soluble fiber diet during pregnancy on them are still underexplored. Sows were allocated to either control or 2.0% pregelatinized waxy maize starch plus guar gum (SF) dietary treatment during gestation. The metabolic characteristics, gut permeability and inflammation status, and gut microbiota composition and metabolism of sows during pregnancy and lactation were analysed. The plasma levels of hs-CRP and HOMA-IR values were increased in days 109 of gestation (G109) and days 3 of lactation (L3), while dietary SF reduced plasma hs-CRP concentrations and the HOMA-IR values. The levels of plasma zonulin and fecal endotoxin and lipocalin-2 were increased in G109 and L3, while dietary SF reduced elevation of plasma zonulin and endotoxin and fecal lipocalin-2. Next-generation sequencing analysis revealed that dietary SF increased levels of butyrate-producing Ruminococcaceae, Lachnospiraceae, and Oscillospira. The fecal and plasma levels of butyrate were also increased. Additionally, the increased relative abundances of Lachnospiraceae in SF sows negatively correlated with plasma hs-CRP and HOMA-IR while Oscillospira was negatively fecal lipocalin-2. Our data reveal that the sow exhibits a metabolic syndrome and dramatical changes in gut microbiota during perinatal period. Besides, dietary SF has beneficial effects on insulin sensitivity, intestinal permeability and inflammation maybe via increasing butyrate-producing bacteria and butyrate production.
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Zhang, Jianghui, Yuan Wang, Guimei Chen, Hongli Wang, Liang Sun, Dongmei Zhang, Fangbiao Tao, Zhihua Zhang, and Linsheng Yang. "The Associations between Multiple Essential Metal(loid)s and Gut Microbiota in Chinese Community-Dwelling Older Adults." Nutrients 15, no. 5 (February 24, 2023): 1137. http://dx.doi.org/10.3390/nu15051137.
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Several experimental studies have suggested that individual essential metal(loid)s (EMs) could regulate the gut microbiota. However, human studies assessing the associations between EMs and gut microbiota are limited. This study aimed to examine the associations of individual and multiple EMs with the compositions of the gut microbiota in older adults. A total of 270 Chinese community-dwelling people over 60 years old were included in this study. Urinary concentrations of selected EMs, including vanadium (V), cobalt (Co), selenium (Se), strontium (Sr), magnesium (Mg), calcium (Ca), and molybdenum (Mo), were examined by inductively coupled plasma mass spectrometry. The gut microbiome was assessed using the 16S rRNA gene sequencing analysis. The zero-inflated probabilistic principal components analysis PCA (ZIPPCA) model was performed to denoise substantial noise in microbiome data. Linear regression and the Bayesian Kernel Machine Regression (BKMR) models were utilized to determine the associations between urine EMs and gut microbiota. No significant association between urine EMs and gut microbiota was found in the total sample, whereas some significant associations were found in subgroup analyses: Co was negatively associated with the microbial Shannon (β = −0.072, p < 0.05) and the inverse-Simpson (β = −0.045, p < 0.05) indices among urban older adults; Ca (R2 = 0.035) and Sr (R2 = 0.023) exhibited significant associations with the altercations of beta diversity in females, while V (R2 = 0.095) showed a significant association with altercations of beta diversity in those who often drank. Furthermore, the associations between partial EMs and specific bacterial taxa were also found: the negative and linear associations of Mo with Tenericutes, Sr with Bacteroidales, and Ca with Enterobacteriaceae and Lachnospiraceae, and a positive and linear association of Sr with Bifidobacteriales were found. Our findings suggested that EMs may play an important role in maintaining the steady status of gut microbiota. Prospective studies are needed to replicate these findings.
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Miliukhina, I. V., E. I. Ermolenko, A. S. Ivanova, E. V. Gracheva, M. P. Kotyleva, E. A. Agapova, and A. N. Suvorov. "GASTROINTESTINAL DYSFUNCTIONS AND PERIPHERAL INFLAMMATORY CYTOKINES IN PARKINSON’S DISEASES." Medical academic journal 19, no. 1S (December 15, 2019): 93–94. http://dx.doi.org/10.17816/maj191s193-94.
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Parkinson’s disease (PD) is a neurodegenerative disease characterized by α-synucleinopathy, which involves all districts of the brain-gut axis, including the central, autonomic and enteric nervous systems. Previous findings suggest that the intestinal microbiome is altered in PD and is related to motor phenotype. However how dysbiosis arises and whether this feature contributes to PD pathogenesis remains unknown. The aim was to evaluate gut microbiome and the serum cytokine profile in PD. We quantified serum interleukin (IL) levels (IL-1β, IL-6, IL-10, TNF-α, IFN-γ) in 55 PD patients. Study of the fecal samples was performed by real time PCR method and bacteriologically. Discovered the relationship between the intensity of dysbiosis and the level of proinflammatory cytokine IFN-γ, IL-6.We show that disturbances in plasma cytokine level could be more profound in PD patients with altered composition of intestinal microbiota, which may explain the mechanism of influence of microbiota composition on the PD manifestations.
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Galié, Serena, Christopher Papandreou, Pierre Arcelin, David Garcia, Antoni Palau-Galindo, Laia Gutiérrez-Tordera, Àlex Folch, and Mònica Bulló. "Examining the Interaction of the Gut Microbiome with Host Metabolism and Cardiometabolic Health in Metabolic Syndrome." Nutrients 13, no. 12 (November 29, 2021): 4318. http://dx.doi.org/10.3390/nu13124318.
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(1) Background: The microbiota-host cross-talk has been previously investigated, while its role in health is not yet clear. This study aimed to unravel the network of microbial-host interactions and correlate it with cardiometabolic risk factors. (2) Methods: A total of 47 adults with overweight/obesity and metabolic syndrome from the METADIET study were included in this cross-sectional analysis. Microbiota composition (151 genera) was assessed by 16S rRNA sequencing, fecal (m = 203) and plasma (m = 373) metabolites were profiled. An unsupervised sparse generalized canonical correlation analysis was used to construct a network of microbiota-metabolite interactions. A multi-omics score was derived for each cluster of the network and associated with cardiometabolic risk factors. (3) Results: Five multi-omics clusters were identified. Thirty-one fecal metabolites formed these clusters and were correlated with plasma sphingomyelins, lysophospholipids and medium to long-chain acylcarnitines. Seven genera from Ruminococcaceae and a member from the Desulfovibrionaceae family were correlated with fecal and plasma metabolites. Positive correlations were found between the multi-omics scores from two clusters with cholesterol and triglycerides levels. (4) Conclusions: We identified a correlated network between specific microbial genera and fecal/plasma metabolites in an adult population with metabolic syndrome, suggesting an interplay between gut microbiota and host lipid metabolism on cardiometabolic health.
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Liu, Jiyun, Mohammed E. Hefni, Cornelia M. Witthöft, Maria Bergström, Stephen Burleigh, Margareta Nyman, and Frida Hållenius. "Effects of Whole Brown Bean and Its Isolated Fiber Fraction on Plasma Lipid Profile, Atherosclerosis, Gut Microbiota, and Microbiota-Dependent Metabolites in Apoe−/− Mice." Nutrients 14, no. 5 (February 22, 2022): 937. http://dx.doi.org/10.3390/nu14050937.
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The health benefits of bean consumption are widely recognized and are largely attributed to the dietary fiber content. This study investigated and compared the effects of whole brown beans and an isolated bean dietary fiber fraction on the plasma lipid profile, atherosclerotic plaque amount, gut microbiota, and microbiota-dependent metabolites (cecal short-chain fatty acids (SCFAs) and plasma methylamines) in Apoe−/− mice fed high fat diets for 10.5 weeks. The results showed that both whole bean and the isolated fiber fraction had a tendency to lower atherosclerotic plaque amount, but not plasma lipid concentration. The whole bean diet led to a significantly higher diversity of gut microbiota compared with the high fat diet. Both bean diets resulted in a lower Firmicutes/Bacteroidetes ratio, higher relative abundance of unclassified S24-7, Prevotella, Bifidobacterium, and unclassified Clostridiales, and lower abundance of Lactobacillus. Both bean diets resulted in higher formation of all cecal SCFAs (higher proportion of propionic acid and lower proportion of acetic acid) and higher plasma trimethylamine N-oxide concentrations compared with the high fat diet. Whole beans and the isolated fiber fraction exerted similar positive effects on atherosclerotic plaque amount, gut microbiota, and cecal SCFAs in Apoe−/− mice compared with the control diets.
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Hasan, Rida Abid, Laura Coughlin, Nicole Poulides, Xiaowei Zhan, Ayesha Zia, and Andrew Y. Koh. "Gut Microbiota Dysbiosis and Elevated Lipopolysaccharide Serum Levels Are Associated with Venous Thromboembolism in Pediatric Patients." Blood 136, Supplement 1 (November 5, 2020): 6–7. http://dx.doi.org/10.1182/blood-2020-134335.
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Background: Pediatric venous thromboembolism (VTE) is a burgeoning clinical problem. As such, there is an urgent need to identify modifiable host factors to prevent VTE and its long-term adverse effects. The gut microbiome, which can influence host physiology and is implicated in the pathogenesis of several disease states, is one such potentially modifiable host factor. Gut microbiota dysbiosis is an imbalance in the composition of the gut microbiota that often manifests as an overabundance of gram-negative bacteria. Lipopolysaccharide (LPS), the glycolipid on the outer membrane of gram-negative bacteria and a heat stable endotoxin, can cross the gut epithelial barrier into the systemic circulation, where it leads to the activation of inflammatory and coagulation pathways. The association of gut microbiota dysbiosis and VTE has not been fully explored. Objective/Hypothesis: The aims of this study were to determine if patients who develop VTE have 1) a distinct microbiota signature with an expansion of gram-negative bacteria, 2) increased systemic levels of LPS and 3) hypercoagulability as compared to controls without VTE. Methods: In this case-control study, we obtained plasma and fecal samples on newly diagnosed VTE pediatric patients and age-matched controls. Gut microbiome profiling was performed on fecal gDNA (16S rRNA sequencing, V4 region; QIIME2 software for gut microbiota taxonomic composition determination). We measured LPS levels using a sandwich ELISA assay (Cusabio) and hypercoagulability using endogenous thrombin potential (ETP) on thrombin generation assay (Calibrated automated thrombogram) on plasma samples. Results: 31 VTE patients were enrolled, of which 18 had fecal samples, and 22 had plasma samples. The median age of VTE cases was 11.0 years (range 1.0 to 19.0 years) of which 51% had underlying medical comorbidities and 48% had antibiotic exposure 30 days prior to the VTE episode. 5 controls were enrolled with a median age of 14.0 years (range 1.0 to 14.0 years). VTE cases had significant enrichment of commensal gram-negative bacteria Bacteroidetes (median 44% relative abundance compared to 21% in controls, p=0.006, Mann-Whitney) and depletion of commensal gram-positive Actinobacteria (median of 2% vs. 10% in controls, p=0.04, Mann-Whitney). Taxonomic differential abundance by linear analysis coupled with effective side measurements (LEfSe) further confirmed these findings by identifying two specific Bacteroidetes species as being enriched in patients with VTE: Bacteroides stercoris and Bacteroides vulgatus (p= 0.01 and 0.02 respectively, Kruskal-Wallis). VTE patients had significantly higher plasma levels of LPS (n=22; mean, 64.30 ng/mL; +SEM 10.17ng/mL) compared to controls (n=5; mean, 14.75ng/mL; +SEM 6.18ng/mL; p=0.03, t-test). Furthermore, VTE cases had increased ETP (n=15; mean, 1922nM.min; +SEM 144.5nM.min) compared to controls (n=5; mean, 1293nM.min; +SEM 78.11nM.min; p=0.02, t-test). Conclusion: We present the first description of elevated LPS levels, hypercoagulability, and a concomitant gut microbiota enrichment of commensal gram-negative bacteria in pediatric patients experiencing an acute VTE episode. Our findings suggest that enrichment of commensal gram-negative bacteria in pediatric patients and LPS gut translocation could play a role in hypercoagulability and the development of VTE. Disclosures Koh: Mesoblast: Consultancy; Prolacta: Consultancy; Merck: Research Funding; Novartis: Research Funding.
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Terrisse, Safae, Lisa Derosa, Valerio Iebba, François Ghiringhelli, Ines Vaz-Luis, Guido Kroemer, Marine Fidelle, et al. "Intestinal microbiota influences clinical outcome and side effects of early breast cancer treatment." Cell Death & Differentiation 28, no. 9 (May 7, 2021): 2778–96. http://dx.doi.org/10.1038/s41418-021-00784-1.
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AbstractThe prognosis of early breast cancer (BC) relies on cell autonomous and immune parameters. The impact of the intestinal microbiome on clinical outcome has not yet been evaluated. Shotgun metagenomics was used to determine the composition of the fecal microbiota in 121 specimens from 76 early BC patients, 45 of whom were paired before and after chemotherapy. These patients were enrolled in the CANTO prospective study designed to record the side effects associated with the clinical management of BC. We analyzed associations between baseline or post-chemotherapy fecal microbiota and plasma metabolomics with BC prognosis, as well as with therapy-induced side effects. We examined the clinical relevance of these findings in immunocompetent mice colonized with BC patient microbiota that were subsequently challenged with histo-compatible mouse BC and chemotherapy. We conclude that specific gut commensals that are overabundant in BC patients compared with healthy individuals negatively impact BC prognosis, are modulated by chemotherapy, and may influence weight gain and neurological side effects of BC therapies. These findings obtained in adjuvant and neoadjuvant settings warrant prospective validation.
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Żak-Gołąb, Agnieszka, Piotr Kocełak, Małgorzata Aptekorz, Maria Zientara, Łukasz Juszczyk, Gayane Martirosian, Jerzy Chudek, and Magdalena Olszanecka-Glinianowicz. "Gut Microbiota, Microinflammation, Metabolic Profile, and Zonulin Concentration in Obese and Normal Weight Subjects." International Journal of Endocrinology 2013 (2013): 1–9. http://dx.doi.org/10.1155/2013/674106.
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The association between gut microbiota and circulating zonulin level, a marker of intestinal permeability, has not been studied yet. The aim of the study is the assessment of plasma zonulin, haptoglobin and proinflammatory cytokines (TNF-αand IL-6) levels in relation to composition of gut microbiota in obese and normal weight subjects. Circulating inflammation markers, such as TNF-α, sTNFR1, sTNFR2, IL-6, zonulin, and haptoglobin levels were measured and semiquantitative analysis of gut microbiota composition was carried out in 50 obese and 30 normal weight subjects without concomitant diseases. Higher circulating zonulin, TNF-α, sTNFR1, sTNFR2, and IL-6 levels were found in the obese subjects. Plasma zonulin level correlated positively with age (r=0.43,P<0.001), body mass (r=0.30,P<0.01), BMI (r=0.33,P<0.01), fat mass and fat percentage (r=0.31,P<0.01andr=0.23,P<0.05, resp.). Positive correlations between bacterial colony count and sTNFR1 (r=0.33,P<0.01) and plasma zonulin (r=0.26,P<0.05) but not haptoglobin levels were found. Additionally, plasma zonulin level was proportional to daily energy intake (r=0.27,P<0.05) and serum glucose concentration (r=0.18,P<0.05) and inversely proportional to diet protein percentage (r=-0.23,P<0.05). Gut microbiota-related systemic microinflammation in the obese is reflected by circulating zonulin level, a potential marker of interstitial permeability.
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Dekkers, Koen F., Sergi Sayols-Baixeras, Gabriel Baldanzi, Christoph Nowak, Ulf Hammar, Diem Nguyen, Georgios Varotsis, et al. "An online atlas of human plasma metabolite signatures of gut microbiome composition." Nature Communications 13, no. 1 (September 23, 2022). http://dx.doi.org/10.1038/s41467-022-33050-0.
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AbstractHuman gut microbiota produce a variety of molecules, some of which enter the bloodstream and impact health. Conversely, dietary or pharmacological compounds may affect the microbiota before entering the circulation. Characterization of these interactions is an important step towards understanding the effects of the gut microbiota on health. In this cross-sectional study, we used deep metagenomic sequencing and ultra-high-performance liquid chromatography linked to mass spectrometry for a detailed characterization of the gut microbiota and plasma metabolome, respectively, of 8583 participants invited at age 50 to 64 from the population-based Swedish CArdioPulmonary bioImage Study. Here, we find that the gut microbiota explain up to 58% of the variance of individual plasma metabolites and we present 997 associations between alpha diversity and plasma metabolites and 546,819 associations between specific gut metagenomic species and plasma metabolites in an online atlas (https://gutsyatlas.serve.scilifelab.se/). We exemplify the potential of this resource by presenting novel associations between dietary factors and oral medication with the gut microbiome, and microbial species strongly associated with the uremic toxin p-cresol sulfate. This resource can be used as the basis for targeted studies of perturbation of specific metabolites and for identification of candidate plasma biomarkers of gut microbiota composition.
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Bourdeau-Julien, Isabelle, Sophie Castonguay-Paradis, Gabrielle Rochefort, Julie Perron, Benoît Lamarche, Nicolas Flamand, Vincenzo Di Marzo, Alain Veilleux, and Frédéric Raymond. "The diet rapidly and differentially affects the gut microbiota and host lipid mediators in a healthy population." Microbiome 11, no. 1 (February 11, 2023). http://dx.doi.org/10.1186/s40168-023-01469-2.
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Abstract Background Bioactive lipids produced by human cells or by the gut microbiota might play an important role in health and disease. Dietary intakes are key determinants of the gut microbiota, its production of short-chain (SCFAs) and branched-chain fatty acids (BCFAs), and of the host endocannabinoidome signalling, which are all involved in metabolic diseases. This hypothesis-driven longitudinal fixed sequence nutritional study, realized in healthy participants, was designed to determine if a lead-in diet affects the host response to a short-term dietary intervention. Participants received a Mediterranean diet (MedDiet) for 3 days, a 13-day lead-in controlled diet reflecting the average Canadian dietary intake (CanDiet), and once again a MedDiet for 3 consecutive days. Fecal and blood samples were collected at the end of each dietary phase to evaluate alterations in gut microbiota composition and plasma levels of endocannabinoidome mediators, SCFAs, and BCFAs. Results We observed an immediate and reversible modulation of plasma endocannabinoidome mediators, BCFAs, and some SCFAs in response to both diets. BCFAs were more strongly reduced by the MedDiet when the latter was preceded by the lead-in CanDiet. The gut microbiota response was also immediate, but not all changes due to the CanDiet were reversible following a short dietary MedDiet intervention. Higher initial microbiome diversity was associated with reduced microbiota modulation after short-term dietary interventions. We also observed that BCFAs and 2-monoacylglycerols had many, but distinct, correlations with gut microbiota composition. Several taxa modulated by dietary intervention were previously associated to metabolic disorders, warranting the need to control for recent diet in observational association studies. Conclusions Our results indicate that lipid mediators involved in the communication between the gut microbiota and host metabolism exhibit a rapid response to dietary changes, which is also the case for some, but not all, microbiome taxa. The lead-in diet influenced the gut microbiome and BCFA, but not the endocannabinoidome, response to the MedDiet. A higher initial microbiome diversity favored the stability of the gut microbiota in response to dietary changes. This study highlights the importance of considering the previous diet in studies relating the gut microbiome with lipid signals involved in host metabolism.
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Wang, Tingting, Lizhang Chen, Peng Huang, Tubao Yang, Senmao Zhang, Lijuan Zhao, Letao Chen, Ziwei Ye, Liu Luo, and Jiabi Qin. "Association of maternal gut microbiota and plasma metabolism with congenital heart disease in offspring: a multi-omic analysis." Scientific Reports 11, no. 1 (March 5, 2021). http://dx.doi.org/10.1038/s41598-021-84901-7.
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AbstractCongenital heart disease (CHD) is the most common congenital disorder diagnosed in newborns. Although lots of related studies have been published, yet the pathogenesis has not been fully elucidated. A growing body of evidence indicates perturbations of the gut microbiota may contribute in a significant way to the development of obesity and diabetes. Given that maternal obesity and diabetes are well-known risk factors for CHD, maternal gut microbiota may be considered as one of the environmental factors involved in the pathogenesis of CHD. The object of this study is to explore the association between maternal gut microbiota and risk of congenital heart disease (CHD) in offspring, as well as the possible mechanisms linking gut microbiota and disease risk. A case–control study was conducted in mothers of infants with CHD (n = 101) and mothers of infants without CHD (n = 95). By applying 16S rRNA gene sequencing and metabolic approaches to 196 stool and plasma samples, we determined microbiome and metabolome profiles in mothers of infants with CHD and controls, and their association with risk of CHD in offspring. The gut microbiome of mothers of infants with CHD was characterized with lower alpha-diversity and distinct overall microbial composition compared with mothers of infants without CHD. A distinct different metabolic profile was found between mothers of infants with CHD and controls. After controlling for the possible confounders, thirty-four bacterial genera and fifty-three plasma metabolites showed distinct abundances between the two groups. The results of the Spearman correlation analyses revealed a great number of significant correlations between the abundant bacterial genera and differentially expressed metabolites. In particular, the genus Bifidobacterium and Streptococcus showed comparable moderate positive correlations with a range of metabolites that involved in lipid metabolism pathway. Our findings suggest that perturbations of maternal gut microbiota and plasma metabolites may be associated with risk of CHD in offspring, and co-variation between microbiota and metabolites may play a part in the linkage between gut microbiota and risk of CHD in offspring.