Journal articles on the topic 'Novel gut-microbiome'
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Asnicar, Francesco, Emily R. Leeming, Eirini Dimidi, Mohsen Mazidi, Paul W. Franks, Haya Al Khatib, Ana M. Valdes, et al. "Blue poo: impact of gut transit time on the gut microbiome using a novel marker." Gut 70, no. 9 (March 15, 2021): 1665–74. http://dx.doi.org/10.1136/gutjnl-2020-323877.
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Background and aimsGut transit time is a key modulator of host–microbiome interactions, yet this is often overlooked, partly because reliable methods are typically expensive or burdensome. The aim of this single-arm, single-blinded intervention study is to assess (1) the relationship between gut transit time and the human gut microbiome, and (2) the utility of the ‘blue dye’ method as an inexpensive and scalable technique to measure transit time.MethodsWe assessed interactions between the taxonomic and functional potential profiles of the gut microbiome (profiled via shotgun metagenomic sequencing), gut transit time (measured via the blue dye method), cardiometabolic health and diet in 863 healthy individuals from the PREDICT 1 study.ResultsWe found that gut microbiome taxonomic composition can accurately discriminate between gut transit time classes (0.82 area under the receiver operating characteristic curve) and longer gut transit time is linked with specific microbial species such as Akkermansia muciniphila, Bacteroides spp and Alistipes spp (false discovery rate-adjusted p values <0.01). The blue dye measure of gut transit time had the strongest association with the gut microbiome over typical transit time proxies such as stool consistency and frequency.ConclusionsGut transit time, measured via the blue dye method, is a more informative marker of gut microbiome function than traditional measures of stool consistency and frequency. The blue dye method can be applied in large-scale epidemiological studies to advance diet-microbiome-health research. Clinical trial registry website https://clinicaltrials.gov/ct2/show/NCT03479866 and trial number NCT03479866.
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Cheng, Chak Kwong, and Yu Huang. "The gut-cardiovascular connection: new era for cardiovascular therapy." Medical Review 1, no. 1 (October 1, 2021): 23–46. http://dx.doi.org/10.1515/mr-2021-0002.
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Abstract Our gut microbiome is constituted by trillions of microorganisms including bacteria, archaea and eukaryotic microbes. Nowadays, gut microbiome has been gradually recognized as a new organ system that systemically and biochemically interact with the host. Accumulating evidence suggests that the imbalanced gut microbiome contributes to the dysregulation of immune system and the disruption of cardiovascular homeostasis. Specific microbiome profiles and altered intestinal permeability are often observed in the pathophysiology of cardiovascular diseases. Gut-derived metabolites, toxins, peptides and immune cell-derived cytokines play pivotal roles in the induction of inflammation and the pathogenesis of dysfunction of heart and vasculature. Impaired crosstalk between gut microbiome and multiple organ systems, such as gut-vascular, heart-gut, gut-liver and brain-gut axes, are associated with higher cardiovascular risks. Medications and strategies that restore healthy gut microbiome might therefore represent novel therapeutic options to lower the incidence of cardiovascular and metabolic disorders.
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Yang, Letao, Lin Y. Hung, Yuefei Zhu, Suwan Ding, Kara G. Margolis, and Kam W. Leong. "Material Engineering in Gut Microbiome and Human Health." Research 2022 (July 21, 2022): 1–32. http://dx.doi.org/10.34133/2022/9804014.
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Tremendous progress has been made in the past decade regarding our understanding of the gut microbiome’s role in human health. Currently, however, a comprehensive and focused review marrying the two distinct fields of gut microbiome and material research is lacking. To bridge the gap, the current paper discusses critical aspects of the rapidly emerging research topic of “material engineering in the gut microbiome and human health.” By engaging scientists with diverse backgrounds in biomaterials, gut-microbiome axis, neuroscience, synthetic biology, tissue engineering, and biosensing in a dialogue, our goal is to accelerate the development of research tools for gut microbiome research and the development of therapeutics that target the gut microbiome. For this purpose, state-of-the-art knowledge is presented here on biomaterial technologies that facilitate the study, analysis, and manipulation of the gut microbiome, including intestinal organoids, gut-on-chip models, hydrogels for spatial mapping of gut microbiome compositions, microbiome biosensors, and oral bacteria delivery systems. In addition, a discussion is provided regarding the microbiome-gut-brain axis and the critical roles that biomaterials can play to investigate and regulate the axis. Lastly, perspectives are provided regarding future directions on how to develop and use novel biomaterials in gut microbiome research, as well as essential regulatory rules in clinical translation. In this way, we hope to inspire research into future biomaterial technologies to advance gut microbiome research and gut microbiome-based theragnostics.
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Thye, Angel Yun-Kuan, Yi-Rou Bah, Jodi Woan-Fei Law, Loh Teng-Hern Tan, Ya-Wen He, Sunny-Hei Wong, Sivakumar Thurairajasingam, Kok-Gan Chan, Learn-Han Lee, and Vengadesh Letchumanan. "Gut–Skin Axis: Unravelling the Connection between the Gut Microbiome and Psoriasis." Biomedicines 10, no. 5 (April 30, 2022): 1037. http://dx.doi.org/10.3390/biomedicines10051037.
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Evidence has shown that gut microbiome plays a role in modulating the development of diseases beyond the gastrointestinal tract, including skin disorders such as psoriasis. The gut–skin axis refers to the bidirectional relationship between the gut microbiome and skin health. This is regulated through several mechanisms such as inflammatory mediators and the immune system. Dysregulation of microbiota has been seen in numerous inflammatory skin conditions such as atopic dermatitis, rosacea, and psoriasis. Understanding how gut microbiome are involved in regulating skin health may lead to development of novel therapies for these skin disorders through microbiome modulation, in particularly psoriasis. In this review, we will compare the microbiota between psoriasis patients and healthy control, explain the concept of gut–skin axis and the effects of gut dysbiosis on skin physiology. We will also review the current evidence on modulating gut microbiome using probiotics in psoriasis.
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Katsi, Vasiliki, Matthaios Didagelos, Stamatios Skevofilax, Iakovos Armenis, Athanasios Kartalis, Charalambos Vlachopoulos, Haralambos Karvounis, and Dimitrios Tousoulis. "GUT Microbiome-GUT Dysbiosis-Arterial Hypertension: New Horizons." Current Hypertension Reviews 15, no. 1 (January 29, 2019): 40–46. http://dx.doi.org/10.2174/1573402114666180613080439.
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Arterial hypertension is a progressive cardiovascular syndrome arising from complex and interrelated etiologies. The human microbiome refers to the community of microorganisms that live in or on the human body. They influence human physiology by interfering in several processes such as providing nutrients and vitamins in Phase I and Phase II drug metabolism. The human gut microbiota is represented mainly by Firmicutes and Bacteroidetes and to a lesser degree by Actinobacteria and Proteobacteria, with each individual harbouring at least 160 such species. Gut microbiota contributes to blood pressure homeostasis and the pathogenesis of arterial hypertension through production, modification, and degradation of a variety of microbial-derived bioactive metabolites. Animal studies and to a lesser degree human research has unmasked relative mechanisms, mainly through the effect of certain microbiome metabolites and their receptors, outlining this relationship. Interventions to utilize these pathways, with probiotics, prebiotics, antibiotics and fecal microbiome transplantation have shown promising results. Personalized microbiome-based disease prediction and treatment responsiveness seem futuristic. Undoubtedly, a long way of experimental and clinical research should be pursued to elucidate this novel, intriguing and very promising horizon.
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Howard, Elizabeth J., Tony K. T. Lam, and Frank A. Duca. "The Gut Microbiome: Connecting Diet, Glucose Homeostasis, and Disease." Annual Review of Medicine 73, no. 1 (January 27, 2022): 469–81. http://dx.doi.org/10.1146/annurev-med-042220-012821.
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Type 2 diabetes rates continue to rise unabated, underscoring the need to better understand the etiology and potential therapeutic options available for this disease. The gut microbiome plays a role in glucose homeostasis, and diabetes is associated with alterations in the gut microbiome. Given that consumption of a Western diet is associated with increased metabolic disease, and that a Western diet alters the gut microbiome, it is plausible that changes in the gut microbiota mediate the dysregulation in glucose homeostasis. In this review, we highlight a few of the most significant mechanisms by which the gut microbiome can influence glucose regulation, including changes in gut permeability, gut–brain signaling, and production of bacteria-derived metabolites like short-chain fatty acids and bile acids. A better understanding of these pathways could lead to the development of novel therapeutics to target the gut microbiome in order to restore glucose homeostasis in metabolic disease.
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Patel, Jyoti. "The gut microbiome: a novel cardio-metabolic target?" Cardiovascular Research 115, no. 9 (June 23, 2019): e82-e84. http://dx.doi.org/10.1093/cvr/cvz151.
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Singh, Vishal, Beng San Yeoh, and Matam Vijay-Kumar. "Gut microbiome as a novel cardiovascular therapeutic target." Current Opinion in Pharmacology 27 (April 2016): 8–12. http://dx.doi.org/10.1016/j.coph.2016.01.002.
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Kustrimovic, Natasa, Raffaella Bombelli, Denisa Baci, and Lorenzo Mortara. "Microbiome and Prostate Cancer: A Novel Target for Prevention and Treatment." International Journal of Molecular Sciences 24, no. 2 (January 12, 2023): 1511. http://dx.doi.org/10.3390/ijms24021511.
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Growing evidence of the microbiome’s role in human health and disease has emerged since the creation of the Human Microbiome Project. Recent studies suggest that alterations in microbiota composition (dysbiosis) may play an essential role in the occurrence, development, and prognosis of prostate cancer (PCa), which remains the second most frequent male malignancy worldwide. Current advances in biological technologies, such as high-throughput sequencing, transcriptomics, and metabolomics, have enabled research on the gut, urinary, and intra-prostate microbiome signature and the correlation with local and systemic inflammation, host immunity response, and PCa progression. Several microbial species and their metabolites facilitate PCa insurgence through genotoxin-mediated mutagenesis or by driving tumor-promoting inflammation and dysfunctional immunosurveillance. However, the impact of the microbiome on PCa development, progression, and response to treatment is complex and needs to be fully understood. This review addresses the current knowledge on the host–microbe interaction and the risk of PCa, providing novel insights into the intraprostatic, gut, and urinary microbiome mechanisms leading to PCa carcinogenesis and treatment response. In this paper, we provide a detailed overview of diet changes, gut microbiome, and emerging therapeutic approaches related to the microbiome and PCa. Further investigation on the prostate-related microbiome and large-scale clinical trials testing the efficacy of microbiota modulation approaches may improve patient outcomes while fulfilling the literature gap of microbial–immune–cancer-cell mechanistic interactions.
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MEJÍA-GRANADOS, Diana Marcela, Benjamín VILLASANA-SALAZAR, Ana Carolina COAN, Liara RIZZI, Marcio Luiz Figueredo BALTHAZAR, Alexandre Barcia de GODOI, Amanda Morato do CANTO, et al. "Gut microbiome in neuropsychiatric disorders." Arquivos de Neuro-Psiquiatria 80, no. 2 (February 2022): 192–207. http://dx.doi.org/10.1590/0004-282x-anp-2021-0052.
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ABSTRACT Background: Neuropsychiatric disorders are a significant cause of death and disability worldwide. The mechanisms underlying these disorders include a constellation of structural, infectious, immunological, metabolic, and genetic etiologies. Advances in next-generation sequencing techniques have demonstrated that the composition of the enteric microbiome is dynamic and plays a pivotal role in host homeostasis and several diseases. The enteric microbiome acts as a key mediator in neuronal signaling via metabolic, neuroimmune, and neuroendocrine pathways. Objective: In this review, we aim to present and discuss the most current knowledge regarding the putative influence of the gut microbiome in neuropsychiatric disorders. Methods: We examined some of the preclinical and clinical evidence and therapeutic strategies associated with the manipulation of the gut microbiome. Results: targeted taxa were described and grouped from major studies to each disease. Conclusions: Understanding the complexity of these ecological interactions and their association with susceptibility and progression of acute and chronic disorders could lead to novel diagnostic biomarkers based on molecular targets. Moreover, research on the microbiome can also improve some emerging treatment choices, such as fecal transplantation, personalized probiotics, and dietary interventions, which could be used to reduce the impact of specific neuropsychiatric disorders. We expect that this knowledge will help physicians caring for patients with neuropsychiatric disorders.
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Maki, Katherine A., Narjis Kazmi, Jennifer J. Barb, and Nancy Ames. "The Oral and Gut Bacterial Microbiomes: Similarities, Differences, and Connections." Biological Research For Nursing 23, no. 1 (July 21, 2020): 7–20. http://dx.doi.org/10.1177/1099800420941606.
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Background: The oral cavity is associated with local and systemic diseases, although oral samples are not as commonly studied as fecal samples in microbiome research. There is a gap in understanding between the similarities and differences in oral and gut microbiomes and how they may influence each other. Methods: A scoping literature review was conducted comparing oral and gut microbiome communities in healthy humans. Results: Ten manuscripts met inclusion criteria and were examined. The oral microbiome sites demonstrated great variance in differential bacterial abundance and the oral microbiome had higher alpha diversity as compared to the gut microbiome. Studies using 16S rRNA sequencing analysis resulted in overall community differences between the oral and gut microbiomes when beta diversity was analyzed. Shotgun metagenomics sequencing increased taxonomic resolution to strain level (intraspecies) and demonstrated a greater percentage of shared taxonomy and oral bacterial translocation to the gut microbiome community. Discussion: The oral and gut microbiome bacterial communities may be more similar than earlier research has suggested, when species strain is analyzed through shotgun metagenomics sequencing. The association between oral health and systemic diseases has been widely reported but many mechanisms underlying this relationship are unknown. Although future research is needed, the oral microbiome may be a novel interventional target through its downstream effects on the gut microbiome. As nurse scientists are experts in symptom characterization and phenotyping of patients, they are also well posed to lead research on the connection of the oral microbiome to the gut microbiome in health and disease.
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Shao, Ling, Shen Qian, Jianghong An, and Xiaohua Tan. "Application of Gut Microbiomes in The Diagnosis and Treatment of Cancer." Global Journal of Microbiology 03, no. 0301 (2022): 1–13. http://dx.doi.org/10.46633/gjmic.030101.
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In this study, the gut microbiome was closely related to human health. Changes in intestinal microbial composition promoted carcinogenesis and cancer development. Specific intestinal microorganisms and their metabolites regulated host physiological functions and tumor microenvironment and significantly affected the anti-tumor treatment response and its adverse effects. Gut microbiome-based strategies have shown promising prospects in the diagnosis and treatment of cancer, and many novel intestinal microbiological manipulation strategies have emerged. At the same time, there were many challenges in transforming intestinal microecology research into clinical practice. Key words: Gut microbiome; tumor microbiome; tumor microenvironment; immunotherapy.
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Gilroy, Rachel, Anuradha Ravi, Maria Getino, Isabella Pursley, Daniel L. Horton, Nabil-Fareed Alikhan, Dave Baker, et al. "Extensive microbial diversity within the chicken gut microbiome revealed by metagenomics and culture." PeerJ 9 (April 6, 2021): e10941. http://dx.doi.org/10.7717/peerj.10941.
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Background The chicken is the most abundant food animal in the world. However, despite its importance, the chicken gut microbiome remains largely undefined. Here, we exploit culture-independent and culture-dependent approaches to reveal extensive taxonomic diversity within this complex microbial community. Results We performed metagenomic sequencing of fifty chicken faecal samples from two breeds and analysed these, alongside all (n = 582) relevant publicly available chicken metagenomes, to cluster over 20 million non-redundant genes and to construct over 5,500 metagenome-assembled bacterial genomes. In addition, we recovered nearly 600 bacteriophage genomes. This represents the most comprehensive view of taxonomic diversity within the chicken gut microbiome to date, encompassing hundreds of novel candidate bacterial genera and species. To provide a stable, clear and memorable nomenclature for novel species, we devised a scalable combinatorial system for the creation of hundreds of well-formed Latin binomials. We cultured and genome-sequenced bacterial isolates from chicken faeces, documenting over forty novel species, together with three species from the genus Escherichia, including the newly named species Escherichia whittamii. Conclusions Our metagenomic and culture-based analyses provide new insights into the bacterial, archaeal and bacteriophage components of the chicken gut microbiome. The resulting datasets expand the known diversity of the chicken gut microbiome and provide a key resource for future high-resolution taxonomic and functional studies on the chicken gut microbiome.
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Suther, Cassandra, Matthew D. Moore, Avraham Beigelman, and Yanjiao Zhou. "The Gut Microbiome and the Big Eight." Nutrients 12, no. 12 (December 3, 2020): 3728. http://dx.doi.org/10.3390/nu12123728.
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Food allergies are increasing at an alarming rate, with 6.5% of the general population affected. It has been hypothesized that the increase in allergies stems from the “hygiene hypothesis”. The gut microbiome, a collection of microbiota and their genetic contents from the gastrointestinal tract, has been shown to play a part in the development of food allergies. The Food and Drug Administration requires all regulated food companies to clearly state an inclusion of the major, or “big eight” food allergens on packaging. This review is to provide information on the significant advancements related to the gut microbiome and each of the eight major food allergies individually. Establishment of causal connection between the microbiome and food allergies has uncovered novel mechanisms. New strategies are discussed to prevent future sensitization and reaction through novel treatments involving functional additives and dietary changes that target the microbiome.
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Noh, Ji Yeon, Chia-Shan Wu, Jennifer A. A. DeLuca, Sridevi Devaraj, Arul Jayaraman, Robert C. Alaniz, Xiao-Di Tan, Clinton D. Allred, and Yuxiang Sun. "Novel Role of Ghrelin Receptor in Gut Dysbiosis and Experimental Colitis in Aging." International Journal of Molecular Sciences 23, no. 4 (February 17, 2022): 2219. http://dx.doi.org/10.3390/ijms23042219.
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Chronic low-grade inflammation is a hallmark of aging, which is now coined as inflamm-aging. Inflamm-aging contributes to many age-associated diseases such as obesity, type 2 diabetes, cardiovascular disease, and inflammatory bowel disease (IBD). We have shown that gut hormone ghrelin, via its receptor growth hormone secretagogue receptor (GHS-R), regulates energy metabolism and inflammation in aging. Emerging evidence suggests that gut microbiome has a critical role in intestinal immunity of the host. To determine whether microbiome is an integral driving force of GHS-R mediated immune-metabolic homeostasis in aging, we assessed the gut microbiome profiles of young and old GHS-R global knockout (KO) mice. While young GHS-R KO mice showed marginal changes in Bacteroidetes and Firmicutes, aged GHS-R KO mice exhibited reduced Bacteroidetes and increased Firmicutes, featuring a disease-susceptible microbiome profile. To further study the role of GHS-R in intestinal inflammation in aging, we induced acute colitis in young and aged GHS-R KO mice using dextran sulfate sodium (DSS). The GHS-R KO mice showed more severe disease activity scores, higher proinflammatory cytokine expression, and decreased expression of tight junction markers. These results suggest that GHS-R plays an important role in microbiome homeostasis and gut inflammation during aging; GHS-R suppression exacerbates intestinal inflammation in aging and increases vulnerability to colitis. Collectively, our finding reveals for the first time that GHS-R is an important regulator of intestinal health in aging; targeting GHS-R may present a novel therapeutic strategy for prevention/treatment of aging leaky gut and inflammatory bowel disease.
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Smith, Margaret M., and James Melrose. "Xylan Prebiotics and the Gut Microbiome Promote Health and Wellbeing: Potential Novel Roles for Pentosan Polysulfate." Pharmaceuticals 15, no. 9 (September 16, 2022): 1151. http://dx.doi.org/10.3390/ph15091151.
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This narrative review highlights the complexities of the gut microbiome and health-promoting properties of prebiotic xylans metabolized by the gut microbiome. In animal husbandry, prebiotic xylans aid in the maintenance of a healthy gut microbiome. This prevents the colonization of the gut by pathogenic organisms obviating the need for dietary antibiotic supplementation, a practice which has been used to maintain animal productivity but which has led to the emergence of antibiotic resistant bacteria that are passed up the food chain to humans. Seaweed xylan-based animal foodstuffs have been developed to eliminate ruminant green-house gas emissions by gut methanogens in ruminant animals, contributing to atmospheric pollution. Biotransformation of pentosan polysulfate by the gut microbiome converts this semi-synthetic sulfated disease-modifying anti-osteoarthritic heparinoid drug to a prebiotic metabolite that promotes gut health, further extending the therapeutic profile and utility of this therapeutic molecule. Xylans are prominent dietary cereal components of the human diet which travel through the gastrointestinal tract as non-digested dietary fibre since the human genome does not contain xylanolytic enzymes. The gut microbiota however digest xylans as a food source. Xylo-oligosaccharides generated in this digestive process have prebiotic health-promoting properties. Engineered commensal probiotic bacteria also have been developed which have been engineered to produce growth factors and other bioactive factors. A xylan protein induction system controls the secretion of these compounds by the commensal bacteria which can promote gut health or, if these prebiotic compounds are transported by the vagal nervous system, may also regulate the health of linked organ systems via the gut–brain, gut–lung and gut–stomach axes. Dietary xylans are thus emerging therapeutic compounds warranting further study in novel disease prevention protocols.
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Zając, Marlena, Monika Borowiecka, Dariusz Gruca, Dagmara Buksak, and Wiktor Wróblewski. "Gut Microbiome as a Novel Treatment Strategy for Psoriasis." Journal of Education, Health and Sport 12, no. 9 (September 3, 2022): 407–21. http://dx.doi.org/10.12775/jehs.2022.12.09.046.
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Introduction and purpose: Psoriasis is a skin disease that develops following chronic inflammatory signaling and keratinocyte hyperproliferation. The pathogenesis of psoriasis is compound and not yet fully understood. Several studies concerning gut microbiota composition and its role in disease pathogenesis recently demonstrated significant alterations among psoriatic patients. This study aims to highlight the latest scientific evidence regarding the gut microbiome alterations of psoriatic patients, as well as the state of knowledge in terms of microbiome-targeted therapies as promising preventive and therapeutic tools for psoriasis.
Brief description of the state of knowledge: The current state of knowledge indicates that the main causes of psoriasis may be a genetic predisposition, as well as many immunological and environmental factors, including dysbiosis of the intestinal microflora. The article covers clinical and experimental studies which indicate that gut microbiota dysbiosis concerning diversity as well as the composition of the microbiome is the potential causal factor of psoriasis and the gut microbiota may serve as a promising prevention/therapy target for psoriasis patients.
Conclusions: This review highlighted a strong link between psoriasis and the gut microbiota, to add new knowledge for discovering the relationship between the altered intestinal microbiota in psoriasis patients. Despite all of these interesting findings, there are a lot of limitations and challenges that future studies should face. More precise and greater studies need to be done to fully understand the potential of microbiota-aimed therapies.
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Avery, Ellen G., Hendrik Bartolomaeus, Andras Maifeld, Lajos Marko, Helge Wiig, Nicola Wilck, Stephan P. Rosshart, Sofia K. Forslund, and Dominik N. Müller. "The Gut Microbiome in Hypertension." Circulation Research 128, no. 7 (April 2, 2021): 934–50. http://dx.doi.org/10.1161/circresaha.121.318065.
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The pathogenesis of hypertension is known to involve a diverse range of contributing factors including genetic, environmental, hormonal, hemodynamic and inflammatory forces, to name a few. There is mounting evidence to suggest that the gut microbiome plays an important role in the development and pathogenesis of hypertension. The gastrointestinal tract, which houses the largest compartment of immune cells in the body, represents the intersection of the environment and the host. Accordingly, lifestyle factors shape and are modulated by the microbiome, modifying the risk for hypertensive disease. One well-studied example is the consumption of dietary fibers, which leads to the production of short-chain fatty acids and can contribute to the expansion of anti-inflammatory immune cells, consequently protecting against the progression of hypertension. Dietary interventions such as fasting have also been shown to impact hypertension via the microbiome. Studying the microbiome in hypertensive disease presents a variety of unique challenges to the use of traditional model systems. Integrating microbiome considerations into preclinical research is crucial, and novel strategies to account for reciprocal host-microbiome interactions, such as the wildling mouse model, may provide new opportunities for translation. The intricacies of the role of the microbiome in hypertensive disease is a matter of ongoing research, and there are several technical considerations which should be accounted for moving forward. In this review we provide insights into the host-microbiome interaction and summarize the evidence of its importance in the regulation of blood pressure. Additionally, we provide recommendations for ongoing and future research, such that important insights from the microbiome field at large can be readily integrated in the context of hypertension.
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Priyadarshini, Medha, Kristen Lednovich, Kai Xu, Sophie Gough, Barton Wicksteed, and Brian T. Layden. "FFAR from the Gut Microbiome Crowd: SCFA Receptors in T1D Pathology." Metabolites 11, no. 5 (May 11, 2021): 302. http://dx.doi.org/10.3390/metabo11050302.
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The gut microbiome has emerged as a novel determinant of type 1 diabetes (T1D), but the underlying mechanisms are unknown. In this context, major gut microbial metabolites, short-chain fatty acids (SCFAs), are considered to be an important link between the host and gut microbiome. We, along with other laboratories, have explored how SCFAs and their cognate receptors affect various metabolic conditions, including obesity, type 2 diabetes, and metabolic syndrome. Though gut microbiome and SCFA-level changes have been reported in T1D and in mouse models of the disease, the role of SCFA receptors in T1D remains under explored. In this review article, we will highlight the existing and possible roles of these receptors in T1D pathology. We conclude with a discussion of SCFA receptors as therapeutic targets for T1D, exploring an exciting new potential for novel treatments of glucometabolic disorders.
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Mittal, Ekansh, Grace Cupp, and Youngbok (Abraham) Kang. "Simulating the Effect of Gut Microbiome on Cancer Cell Growth Using a Microfluidic Device." Sensors 23, no. 3 (January 22, 2023): 1265. http://dx.doi.org/10.3390/s23031265.
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The imbalance in the gut microbiome plays a vital role in the progression of many diseases, including cancer, due to increased inflammation in the body. Since gut microbiome-induced inflammation can serve as a novel therapeutic strategy, there is an increasing need to identify novel approaches to investigate the effect of inflammation instigated by gut microbiome on cancer cells. However, there are limited biomimetic co-culture systems that allow testing of the causal relationship of the microbiome on cancer cells. Here we developed a microfluidic chip that can simulate the interaction of the gut microbiome and cancer cells to investigate the effects of bacteria and inflammatory stress on cancer cells in vitro. To test the microfluidic chip, we used colorectal cancer cells, as an increased microbiome abundance has been associated with poor outcomes in colorectal cancer. We cultured colorectal cancer cells with Bacillus bacteria or lipopolysaccharide (LPS), a purified bacterial membrane that induces a significant inflammatory response, in the microfluidic device. Our results showed that both LPS and Bacillus significantly accelerated the growth of colorectal cancer cells, therefore supporting that the increased presence of certain bacteria promotes cancer cell growth. The microfluidic device included in this study may have significant implications in identifying new treatments for various cancer types in the future.
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Kirby, Trevor, and Javier Ochoa-Repáraz. "The Gut Microbiome in Multiple Sclerosis: A Potential Therapeutic Avenue." Medical Sciences 6, no. 3 (August 24, 2018): 69. http://dx.doi.org/10.3390/medsci6030069.
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Recently, there has been a substantial increase in the number of studies focused upon connecting the gut microbiome with cases of central nervous system (CNS) autoimmunity. Multiple sclerosis (MS) is a neurodegenerative autoimmune disorder of the CNS. Recent experimental and clinical evidence suggests the presence of microbial imbalances in the gut of MS sufferers. The gut microbiome is defined as the summation of all the microbial entities as well as their genes, proteins, and metabolic products in a given space and time. Studies show the MS gut microbiome as having general alterations in specific taxa, some associated with the promotion of inflammatory cytokines and overall inflammation. In conjunction with these findings, experimental models of the disease have reported that T regulatory (Treg) cells have deficits in their function as a result of the aberrant gut microbiota composition. The findings suggest that the interactions between the host and the microbiota are reciprocal, although more extensive work is required to confirm this. Moreover, evidence indicates that changes in microbiota composition may result in imbalances that could result in disease, with the gut as a potential novel therapeutic avenue. By understanding the biological effects of aberrant gut microbiome composition, it is possible to contemplate current therapeutic options and their efficacy. Ultimately, more research is necessary in this field, but targeting the gut microbiota may lead to the development of novel therapeutic strategies.
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Gueniche, Audrey, Olivier Perin, Amina Bouslimani, Leslie Landemaine, Namita Misra, Sylvie Cupferman, Luc Aguilar, Cécile Clavaud, Tarun Chopra, and Ahmad Khodr. "Advances in Microbiome-Derived Solutions and Methodologies Are Founding a New Era in Skin Health and Care." Pathogens 11, no. 2 (January 20, 2022): 121. http://dx.doi.org/10.3390/pathogens11020121.
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The microbiome, as a community of microorganisms and their structural elements, genomes, metabolites/signal molecules, has been shown to play an important role in human health, with significant beneficial applications for gut health. Skin microbiome has emerged as a new field with high potential to develop disruptive solutions to manage skin health and disease. Despite an incomplete toolbox for skin microbiome analyses, much progress has been made towards functional dissection of microbiomes and host-microbiome interactions. A standardized and robust investigation of the skin microbiome is necessary to provide accurate microbial information and set the base for a successful translation of innovations in the dermo-cosmetic field. This review provides an overview of how the landscape of skin microbiome research has evolved from method development (multi-omics/data-based analytical approaches) to the discovery and development of novel microbiome-derived ingredients. Moreover, it provides a summary of the latest findings on interactions between the microbiomes (gut and skin) and skin health/disease. Solutions derived from these two paths are used to develop novel microbiome-based ingredients or solutions acting on skin homeostasis are proposed. The most promising skin and gut-derived microbiome interventional strategies are presented, along with regulatory, safety, industrial, and technical challenges related to a successful translation of these microbiome-based concepts/technologies in the dermo-cosmetic industry.
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Gou, Wanglong, Chu-Wen Ling, Yan He, Zengliang Jiang, Yuanqing Fu, Xu Fengzhe, Ze-Lei Miao, et al. "Interpretable Machine Learning Algorithm Reveals Novel Gut Microbiome Features in Predicting Type 2 Diabetes." Current Developments in Nutrition 4, Supplement_2 (May 29, 2020): 1559. http://dx.doi.org/10.1093/cdn/nzaa062_016.
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Abstract Objectives The gut microbiome-type 2 diabetes (T2D) relationship among human cohorts have been controversial. We hypothesized that this limitation could be addressed by integrating the cutting-edge interpretable machine learning framework and large-scale human cohort studies. Methods 3 independent cohorts with >9000 participants were included in this study. We proposed a new machine learning-based analytic framework — using LightGBM to infer the relationship between incorporated features and T2D, and SHapley Additive explanation(SHAP) to identified microbiome features associated with the risk of T2D. We then generated a microbiome risk score (MRS) integrating the threshold and direction of the identified microbiome features to predict T2D risk. Results We finally identified 15 microbiome features (two of them are indicators of microbial diversity, others are taxa-related features) associated with the risk of T2D. The identified T2D-related gut microbiome features showed superior T2D prediction accuracy compared to host genetics or traditional risk factors. Furthermore, we found that the MRS (per unit change in MRS) consistently showed positive association with T2D risk in the discovery cohort (RR 1.28, 95%CI 1.23-1.33), external validation cohort 1 (RR 1.23, 95%CI 1.13-1.34) and external validation cohort 2 (GGMP, RR 1.12, 95%CI 1.06-1.18). The MRS could also predict future glucose increment. We subsequently identified dietary and lifestyle factors which could prospectively modulate the microbiome features, and found that body fat distribution may be the key factor modulating the gut microbiome-T2D relationship. Conclusions Taken together, we proposed a new analytical framework for the investigation of microbiome-disease relationship. The identified microbiome features may serve as potential drug targets for T2D in future. Funding Sources This study was funded by National Natural Science Foundation of China (81903316, 81773416), Westlake University (101396021801) and the 5010 Program for Clinical Researches (2007032) of the Sun Yat-sen University (Guangzhou, China).
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Núñez-Sánchez, María A., Silvia Melgar, Keith O’Donoghue, María A. Martínez-Sánchez, Virgina E. Fernández-Ruiz, Mercedes Ferrer-Gómez, Antonio J. Ruiz-Alcaraz, and Bruno Ramos-Molina. "Crohn’s Disease, Host–Microbiota Interactions, and Immunonutrition: Dietary Strategies Targeting Gut Microbiome as Novel Therapeutic Approaches." International Journal of Molecular Sciences 23, no. 15 (July 28, 2022): 8361. http://dx.doi.org/10.3390/ijms23158361.
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Crohn’s disease (CD) is a complex, disabling, idiopathic, progressive, and destructive disorder with an unknown etiology. The pathogenesis of CD is multifactorial and involves the interplay between host genetics, and environmental factors, resulting in an aberrant immune response leading to intestinal inflammation. Due to the high morbidity and long-term management of CD, the development of non-pharmacological approaches to mitigate the severity of CD has recently attracted great attention. The gut microbiota has been recognized as an important player in the development of CD, and general alterations in the gut microbiome have been established in these patients. Thus, the gut microbiome has emerged as a pre-eminent target for potential new treatments in CD. Epidemiological and interventional studies have demonstrated that diet could impact the gut microbiome in terms of composition and functionality. However, how specific dietary strategies could modulate the gut microbiota composition and how this would impact host–microbe interactions in CD are still unclear. In this review, we discuss the most recent knowledge on host–microbe interactions and their involvement in CD pathogenesis and severity, and we highlight the most up-to-date information on gut microbiota modulation through nutritional strategies, focusing on the role of the microbiota in gut inflammation and immunity.
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May, Stephanie, Samantha Evans, and Lee Parry. "Organoids, organs-on-chips and other systems, and microbiota." Emerging Topics in Life Sciences 1, no. 4 (November 30, 2017): 385–400. http://dx.doi.org/10.1042/etls20170047.
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The human gut microbiome is considered an organ in its entirety and has been the subject of extensive research due to its role in physiology, metabolism, digestion, and immune regulation. Disequilibria of the normal microbiome have been associated with the development of several gastrointestinal diseases, but the exact underlying interactions are not well understood. Conventional in vivo and in vitro modelling systems fail to faithfully recapitulate the complexity of the human host–gut microbiome, emphasising the requirement for novel systems that provide a platform to study human host–gut microbiome interactions with a more holistic representation of the human in vivo microenvironment. In this review, we outline the progression and applications of new and old modelling systems with particular focus on their ability to model and to study host–microbiome cross-talk.
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Utzschneider, Kristina M., Mario Kratz, Chris J. Damman, and Meredith Hullarg. "Mechanisms Linking the Gut Microbiome and Glucose Metabolism." Journal of Clinical Endocrinology & Metabolism 101, no. 4 (April 1, 2016): 1445–54. http://dx.doi.org/10.1210/jc.2015-4251.
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Abstract Context: Type 2 diabetes mellitus is associated with gastrointestinal dysbiosis involving both compositional and functional changes in the gut microbiome. Changes in diet and supplementation with probiotics and prebiotics (ie, fermentable fibers) can induce favorable changes in gut bacterial species and improve glucose homeostasis. Objective: This paper will review the data supporting several potential mechanisms whereby gut dysbiosis contributes to metabolic dysfunction, including microbiota driven increases in systemic lipopolysaccharide concentrations, changes in bile acid metabolism, alterations in short chain fatty acid production, alterations in gut hormone secretion, and changes in circulating branched-chain amino acids. Methods: Data for this review were identified by searching English language references from PubMed and relevant articles. Conclusions: Understanding the mechanisms linking the gut microbiome to glucose metabolism, and the relevant compositional and functional characteristics of the gut microbiome, will help direct future research to develop more targeted approaches or novel compounds aimed at restoring a more healthy gut microbiome as a new approach to prevent and treat type 2 diabetes mellitus and related metabolic conditions.
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Buhaș, Mihaela Cristina, Laura Ioana Gavrilaș, Rareș Candrea, Adrian Cătinean, Andrei Mocan, Doina Miere, and Alexandru Tătaru. "Gut Microbiota in Psoriasis." Nutrients 14, no. 14 (July 20, 2022): 2970. http://dx.doi.org/10.3390/nu14142970.
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Psoriasis is a chronic inflammatory skin disease with autoimmune pathogenic characteristics and is caused by chronic inflammation, which results in uncontrolled keratinocyte growth and defective differentiation. The link between the gut microbiota and immune system regulation opened a novel angle to understand the pathogenesis of many chronic multifactorial diseases, including psoriasis. Current evidence suggests that modulation of the gut microbiota, both through dietary approaches and through supplementation with probiotics and prebiotics, could represent a novel therapeutic approach. The present work aims to highlight the latest scientific evidence regarding the microbiome alterations of psoriatic patients, as well as state of the art insights in terms of microbiome-targeted therapies as promising preventive and therapeutic tools for psoriasis.
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Alexander, James L., and Benjamin H. Mullish. "A Guide to the Gut Microbiome and its Relevance to Critical Care." British Journal of Nursing 29, no. 19 (October 22, 2020): 1106–12. http://dx.doi.org/10.12968/bjon.2020.29.19.1106.
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Although it is well-established that particular bacteria may cause gastroenteritis and other infections when present in the gut, it is only recently that scientists have made significant inroads into understanding the huge number of other bacteria and additional microbes that live within the gastrointestinal tract, referred to as the gut microbiome. In particular, it is now recognised that bacteria within the gut microbiome have a wide variety of roles in maintaining different aspects of human health, and that disturbances of these bacteria may potentially cause or contribute to a number of different medical conditions, including particular infections, certain cancers, and chronic conditions, including inflammatory bowel disease. Moreover, there is increasing awareness that these bacteria help determine how the body responds to medication, including antibiotics and chemotherapy. There has been growing interest in different approaches to alter the gut microbiome as a novel approach to medical therapy. This article provides an overview of the importance of the gut microbiome, with a particular focus on critical care.
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Forkosh, Esther, and Yaron Ilan. "The heart-gut axis: new target for atherosclerosis and congestive heart failure therapy." Open Heart 6, no. 1 (April 2019): e000993. http://dx.doi.org/10.1136/openhrt-2018-000993.
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The human gut microbiota has been identified as a possible novel risk factor for cardiovascular disease. The intestinal microbiome plays a role in the pathogenesis of atherosclerosis and heart failure. Even though studies in rodents suggested that gut microbes may affect the risk of heart disease, this link has not been shown in humans. In the present study, we review several potential mechanisms by which the gut microbiome and bacterial translocation are associated with the development of cardiac disorders making them potential targets for novel therapeutic measures for these conditions. Modulation of the gut microbiota as a mechanism for altering the pathogenesis of disorders is an area of growing interest. Alteration in the gut microbiota is being explored as a method of reducing risk factors associated with cardiac diseases.
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Wallace, David J., Naomi L. Sayre, T. Tyler Patterson, Susannah E. Nicholson, Donald Hilton, and Ramesh Grandhi. "Spinal cord injury and the human microbiome: beyond the brain–gut axis." Neurosurgical Focus 46, no. 3 (March 2019): E11. http://dx.doi.org/10.3171/2018.12.focus18206.
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In addition to standard management for the treatment of the acute phase of spinal cord injury (SCI), implementation of novel neuroprotective interventions offers the potential for significant reductions in morbidity and long-term health costs. A better understanding of the systemic changes after SCI could provide insight into mechanisms that lead to secondary injury. An emerging area of research involves the complex interplay of the gut microbiome and the CNS, i.e., a brain–gut axis, or perhaps more appropriately, a CNS–gut axis. This review summarizes the relevant literature relating to the gut microbiome and SCI. Experimental models in stroke and traumatic brain injury demonstrate the bidirectional communication of the CNS to the gut with postinjury dysbiosis, gastrointestinal-associated lymphoid tissue–mediated neuroinflammatory responses, and bacterial-metabolite neurotransmission. Similar findings are being elucidated in SCI as well. Experimental interventions in these areas have shown promise in improving functional outcomes in animal models. This commensal relationship between the human body and its microbiome, particularly the gut microbiome, represents an exciting frontier in experimental medicine.
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Richards, Elaine M., Jing Li, Bruce R. Stevens, Carl J. Pepine, and Mohan K. Raizada. "Gut Microbiome and Neuroinflammation in Hypertension." Circulation Research 130, no. 3 (February 4, 2022): 401–17. http://dx.doi.org/10.1161/circresaha.121.319816.
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Hypertension is a worldwide problem with major impacts on health including morbidity and mortality, as well as consumption of health care resources. Nearly 50% of American adults have high blood pressure, and this rate is rising. Even with multiple antihypertensive drugs and aggressive lifestyle modifications, blood pressure is inadequately controlled in about 1 of 5 hypertensive individuals. This review highlights a hypothesis for hypertension that suggests alternative mechanisms for blood pressure elevation and maintenance. A better understanding of these mechanisms could open avenues for more successful treatments. The hypothesis accounts for recent understandings of the involvement of gut physiology, gut microbiota, and neuroinflammation in hypertension. It includes bidirectional communication between gut microbiota and gut epithelium in the gut-brain axis that is involved in regulation of autonomic nervous system activity and blood pressure control. Dysfunction of this gut-brain axis, including dysbiosis of gut microbiota, gut epithelial dysfunction, and deranged input to the brain, contributes to hypertension via inflammatory mediators, metabolites, bacteria in the circulation, afferent information alterations, etc resulting in neuroinflammation and unbalanced autonomic nervous system activity that elevates blood pressure. This in turn negatively affects gut function and its microbiota exacerbating the problem. We focus this review on the gut-brain axis hypothesis for hypertension and possible contribution to racial disparities in hypertension. A novel idea, that immunoglobulin A-coated bacteria originating in the gut with access to the brain could be involved in hypertension, is raised. Finally, minocycline, with its anti-inflammatory and antimicrobial properties, is evaluated as a potential antihypertensive drug acting on this axis.
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de Vos, Willem M., Herbert Tilg, Matthias Van Hul, and Patrice D. Cani. "Gut microbiome and health: mechanistic insights." Gut 71, no. 5 (February 1, 2022): 1020–32. http://dx.doi.org/10.1136/gutjnl-2021-326789.
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The gut microbiota is now considered as one of the key elements contributing to the regulation of host health. Virtually all our body sites are colonised by microbes suggesting different types of crosstalk with our organs. Because of the development of molecular tools and techniques (ie, metagenomic, metabolomic, lipidomic, metatranscriptomic), the complex interactions occurring between the host and the different microorganisms are progressively being deciphered. Nowadays, gut microbiota deviations are linked with many diseases including obesity, type 2 diabetes, hepatic steatosis, intestinal bowel diseases (IBDs) and several types of cancer. Thus, suggesting that various pathways involved in immunity, energy, lipid and glucose metabolism are affected.In this review, specific attention is given to provide a critical evaluation of the current understanding in this field. Numerous molecular mechanisms explaining how gut bacteria might be causally linked with the protection or the onset of diseases are discussed. We examine well-established metabolites (ie, short-chain fatty acids, bile acids, trimethylamine N-oxide) and extend this to more recently identified molecular actors (ie, endocannabinoids, bioactive lipids, phenolic-derived compounds, advanced glycation end products and enterosynes) and their specific receptors such as peroxisome proliferator-activated receptor alpha (PPARα) and gamma (PPARγ), aryl hydrocarbon receptor (AhR), and G protein-coupled receptors (ie, GPR41, GPR43, GPR119, Takeda G protein-coupled receptor 5).Altogether, understanding the complexity and the molecular aspects linking gut microbes to health will help to set the basis for novel therapies that are already being developed.
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Gilroy, Rachel, Joy Leng, Anuradha Ravi, Evelien M. Adriaenssens, Aharon Oren, Dave Baker, Roberto M. La Ragione, Christopher Proudman, and Mark J. Pallen. "Metagenomic investigation of the equine faecal microbiome reveals extensive taxonomic diversity." PeerJ 10 (March 23, 2022): e13084. http://dx.doi.org/10.7717/peerj.13084.
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Background The horse plays crucial roles across the globe, including in horseracing, as a working and companion animal and as a food animal. The horse hindgut microbiome makes a key contribution in turning a high fibre diet into body mass and horsepower. However, despite its importance, the horse hindgut microbiome remains largely undefined. Here, we applied culture-independent shotgun metagenomics to thoroughbred equine faecal samples to deliver novel insights into this complex microbial community. Results We performed metagenomic sequencing on five equine faecal samples to construct 123 high- or medium-quality metagenome-assembled genomes from Bacteria and Archaea. In addition, we recovered nearly 200 bacteriophage genomes. We document surprising taxonomic diversity, encompassing dozens of novel or unnamed bacterial genera and species, to which we have assigned new Candidatus names. Many of these genera are conserved across a range of mammalian gut microbiomes. Conclusions Our metagenomic analyses provide new insights into the bacterial, archaeal and bacteriophage components of the horse gut microbiome. The resulting datasets provide a key resource for future high-resolution taxonomic and functional studies on the equine gut microbiome.
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Wang, Shaohua, Bo Wang, Sidharth Mishra, Shalini Jain, Jingzhong Ding, Stephen Krtichevsky, Dalane Kitzman, and Hariom Yadav. "A novel probiotics therapy for aging-related leaky gut and inflammation." Innovation in Aging 5, Supplement_1 (December 1, 2021): 668–69. http://dx.doi.org/10.1093/geroni/igab046.2521.
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Abstract Inflammaging characterized with increased low grade inflammation in older adults is common determinant of unhealthy aging; and is a major risk factor of morbidity and mortality in older adults. The precise origin of inflammation in older adults is not known, however, emerging evidence indicate that increased intestinal epithelial permeability (leaky gut) and abnormal (dysbiotic) gut microbiota could be one of the key source. However, no preventive and treatment therapies are available to reverse the leaky gut and microbiome dysbiosis in older adults. Here, we presented the evidence that a human-origin probiotics cocktail containing 5 Lactobacillus and 5 Enterococcus strains isolated from healthy human infant gut can ameliorate aging-related metabolic, physical and cognitive dysfunctions in older mice. We show that the Feeding this probiotic cocktail prevented high-fat diet–induced (HFD-induced) abnormalities in glycose metabolism and physical functions in older mice and reduced microbiota dysbiosis, leaky gut, inflammation. Probiotic-modulated gut microbiota reduced leaky gut by increasing tight junctions on intestinal epithelia, which in turn reduced inflammation. Mechanistically, probiotics increased bile salt hydrolase activity in older microbiota, which in turn increased taurine deconjugation from bile acids to increase free taurine abundance in the gut. We further show that taurine stimulated tight junctions and suppressed gut leakiness. Further, taurine increased life span, reduced adiposity and leaky gut, and enhanced physical function in Caenorhabditis elegans. Whether this novel human origin probiotic therapy could prevent or treat aging-related leaky gut and inflammation in the elderly by reversing microbiome dysbiosis requires evaluation.
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Mohamed, Ali, Harry Menon, Marina Chulkina, Nelson S. Yee, and Irina V. Pinchuk. "Drug–Microbiota Interaction in Colon Cancer Therapy: Impact of Antibiotics." Biomedicines 9, no. 3 (March 5, 2021): 259. http://dx.doi.org/10.3390/biomedicines9030259.
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Colon adenocarcinoma is one of the most common malignancies, and it is highly lethal. Chemotherapy plays an important role in the treatment of colon cancer at various stages of the disease. The gut microbiome has emerged as a key player in colon cancer development and progression, and it can also alter the therapeutic agent’s efficacy and toxicities. Antibiotics can directly and/or indirectly affect the balance of the gut microbiome and, therefore, the clinical outcomes. In this article, we provided an overview of the composition of the gut microbiome under homeostasis and the mechanistic links between gut microbiota and colon cancer. The relationship between the use of oral antibiotics and colon cancer, as well as the impact of the gut microbiome on the efficacy and toxicities of chemotherapy in colon cancer, are discussed. Potential interventions to modulate microbiota and improve chemotherapy outcomes are discussed. Further studies are indicated to address these key gaps in the field and provide a scientific basis for the design of novel microbiota-based approaches for prevention/use as adjuvant therapeutics for patients with colon cancer.
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Rezasoltani, Sama, Dorrieh Ahmadi Bashirzadeh, Ehsan Nazemalhosseini Mojarad, Hamid Asadzadeh Aghdaei, Mohsen Norouzinia, and Shabnam Shahrokh. "Signature of Gut Microbiome by Conventional and Advanced Analysis Techniques: Advantages and Disadvantages." Middle East Journal of Digestive Diseases 12, no. 1 (December 12, 2019): 5–11. http://dx.doi.org/10.15171/mejdd.2020.157.
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Gut microbiota is considered as a human organ with its own specific functions and complexity. Development of novel techniques such as shut gun sequencing, metagenomics, and next-generation sequencing (NGS) has enabled bypassing the traditional culturedependent bias and has significantly expanded our understanding of the composition, diversity, and roles of the gut microbiota in human health and diseases. Although amplicon sequencing characterizes the taxonomic composition of the gut microbiome, it is impossible to cover the direct evidence of the microbial biological functions related to the gut microbial community. Hence, the critical next step for gut microbiome studies is shifting from gene/ genome-centric analysis to mechanism-centric techniques by integrating omics data with experimental results. Realizing gut microbial diversity and their bioactive metabolites function will provide insight into the clinical application of gut microbiota in diagnoses and treatments of several diseases. In this review, we focused on explaining the conventional and advanced microbiome analysis techniques regarding gut microbiota investigation with considering the advantages and disadvantages of the platforms.
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Wang, Yiwei, Chi Tung Choy, Yufeng Lin, Lin Wang, Jinpao Hou, Joseph Chi Ching Tsui, Junwei Zhou, et al. "Effect of a Novel E3 Probiotics Formula on the Gut Microbiome in Atopic Dermatitis Patients: A Pilot Study." Biomedicines 10, no. 11 (November 11, 2022): 2904. http://dx.doi.org/10.3390/biomedicines10112904.
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Atopic dermatitis (AD) has been shown to be closely related to gut dysbiosis mediated through the gut–skin axis, and thus the gut microbiome has recently been explored as a potential therapeutic target for the treatment of AD. Contrasting and varying efficacy have been reported since then. In order to investigate the determining factor of probiotics responsiveness in individuals with AD, we initiated the analysis of 41 AD patients with varying disease severity in Hong Kong, whereas the severity was assessed by Eczema Area and Severity Index (EASI) by board certified dermatologist. 16S rRNA sequencing on the fecal samples from AD patients were performed to obtain the metagenomics profile at baseline and after 8 weeks of oral administration of a novel E3 probiotics formula (including prebiotics, probiotics and postbiotics). While EASI of the participants were significantly lower after the probiotics treatment (p < 0.001, paired Wilcoxon signed rank), subjects with mild AD were found to be more likely to respond to the probiotics treatment. Species richness among responders regardless of disease severity were significantly increased (p < 0.001, paired Wilcoxon signed rank). Responders exhibited (1) elevated relative abundance of Clostridium, Fecalibacterium, Lactobacillus, Romboutsia, and Streptococcus, (2) reduced relative abundance of Collinsella, Bifidobacterium, Fusicatenibacter, and Escherichia-Shigella amid orally-intake probiotics identified using the machine learning algorithm and (3) gut microbiome composition and structure resembling healthy subjects after probiotics treatment. Here, we presented the gut microbiome dynamics in AD patients after the administration of the E3 probiotics formula and delineated the unique gut microbiome signatures in individuals with AD who were responding to the probiotics. These findings could guide the future development of probiotics use for AD management.
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Siddiqui, Ruqaiyyah, Zinb Makhlouf, Ahmad M. Alharbi, Hasan Alfahemi, and Naveed Ahmed Khan. "The Gut Microbiome and Female Health." Biology 11, no. 11 (November 21, 2022): 1683. http://dx.doi.org/10.3390/biology11111683.
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The possession of two X chromosomes may come with the risk of various illnesses, females are more likely to be affected by osteoarthritis, heart disease, and anxiety. Given the reported correlations between gut microbiome dysbiosis and various illnesses, the female gut microbiome is worthy of exploration. Herein, we discuss the composition of the female gut microbiota and its dysbiosis in pathologies affecting the female population. Using PubMed, we performed a literature search, using key terms, namely: “gut microbiome”, “estrogen”, “menopause”, “polycystic ovarian syndrome”, “pregnancy”, and “menstruation”. In polycystic ovarian syndrome (PCOS), the abundance of Bacteroides vulgatus, Firmicutes, Streptococcus, and the ratio of Escherichia/Shigella was found to be increased while that of Tenericutes ML615J-28, Tenericutes 124-7, Akkermansia, Ruminococcaceae, and Bacteroidetes S24-7 was reduced. In breast cancer, the abundance of Clostridiales was enhanced, while in cervical cancer, Prevotella, Porphyromonas, and Dialister were enhanced but Bacteroides, Alistipes, and members of Lachnospiracea, were decreased. In ovarian cancer, Prevotella abundance was increased. Interestingly, the administration of Lactobacillus acidophilus, Bifidobacterium bifidum, Lactobacillus reuteri, and Lactobacillus fermentum ameliorated PCOS symptoms while that of a mix of Bifidobacterium lactis W51, Bifidobacterium bifidum W23, Lactobacillus brevis W63, Bifidobacterium lactis W52, Lactobacillus salivarius W24, Lactobacillus acidophilus W37, Lactococcus lactis W19, Lactobacillus casei W56, and Lactococcus lactis W58 alleviated vascular malfunction and arterial stiffness in obese postmenopausal women, and finally, while further research is needed, Prevotella maybe protective against postmenopausal bone mass loss. As several studies report the therapeutic potential of probiotics and since the gut microbiota of certain female pathological states has been relatively characterized, we speculate that the administration of certain bacterial species as probiotics is warranted, as novel independent or adjunct therapies for various female pathologies.
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Kaliannan, Kanakaraju, Shane O. Donnell, Kiera Murphy, Catherine Stanton, Chao Kang, Bin Wang, Xiang-Yong Li, Atul K. Bhan, and Jing X. Kang. "Decreased Tissue Omega-6/Omega-3 Fatty Acid Ratio Prevents Chemotherapy-Induced Gastrointestinal Toxicity Associated with Alterations of Gut Microbiome." International Journal of Molecular Sciences 23, no. 10 (May 10, 2022): 5332. http://dx.doi.org/10.3390/ijms23105332.
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Gastrointestinal toxicity (GIT) is a debilitating side effect of Irinotecan (CPT-11) and limits its clinical utility. Gut dysbiosis has been shown to mediate this side effect of CPT-11 by increasing gut bacterial β-glucuronidase (GUSB) activity and impairing the intestinal mucosal barrier (IMB). We have recently shown the opposing effects of omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) on the gut microbiome. We hypothesized that elevated levels of tissue n-3 PUFA with a decreased n-6/n-3 PUFA ratio would reduce CPT-11-induced GIT and associated changes in the gut microbiome. Using a unique transgenic mouse (FAT-1) model combined with dietary supplementation experiments, we demonstrate that an elevated tissue n-3 PUFA status with a decreased n-6/n-3 PUFA ratio significantly reduces CPT-11-induced weight loss, bloody diarrhea, gut pathological changes, and mortality. Gut microbiome analysis by 16S rRNA gene sequencing and QIIME2 revealed that improvements in GIT were associated with the reduction in the CPT-11-induced increase in both GUSB-producing bacteria (e.g., Enterobacteriaceae) and GUSB enzyme activity, decrease in IMB-maintaining bacteria (e.g., Bifidobacterium), IMB dysfunction and systemic endotoxemia. These results uncover a host–microbiome interaction approach to the management of drug-induced gut toxicity. The prevention of CPT-11-induced gut microbiome changes by decreasing the tissue n-6/n-3 PUFA ratio could be a novel strategy to prevent chemotherapy-induced GIT.
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Culligan, Eamonn P., Julian R. Marchesi, Colin Hill, and Roy D. Sleator. "Mining the human gut microbiome for novel stress resistance genes." Gut Microbes 3, no. 4 (July 14, 2012): 394–97. http://dx.doi.org/10.4161/gmic.20984.
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Yang, Yongshou, Jinhu Tian, and Bo Yang. "Targeting gut microbiome: A novel and potential therapy for autism." Life Sciences 194 (February 2018): 111–19. http://dx.doi.org/10.1016/j.lfs.2017.12.027.
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Villéger, Romain, Amélie Lopès, Guillaume Carrier, Julie Veziant, Elisabeth Billard, Nicolas Barnich, Johan Gagnière, Emilie Vazeille, and Mathilde Bonnet. "Intestinal Microbiota: A Novel Target to Improve Anti-Tumor Treatment?" International Journal of Molecular Sciences 20, no. 18 (September 17, 2019): 4584. http://dx.doi.org/10.3390/ijms20184584.
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Recently, preclinical and clinical studies targeting several types of cancer strongly supported the key role of the gut microbiota in the modulation of host response to anti-tumoral therapies such as chemotherapy, immunotherapy, radiotherapy and even surgery. Intestinal microbiome has been shown to participate in the resistance to a wide range of anticancer treatments by direct interaction with the treatment or by indirectly stimulating host response through immunomodulation. Interestingly, these effects were described on colorectal cancer but also in other types of malignancies. In addition to their role in therapy efficacy, gut microbiota could also impact side effects induced by anticancer treatments. In the first part of this review, we summarized the role of the gut microbiome on the efficacy and side effects of various anticancer treatments and underlying mechanisms. In the second part, we described the new microbiota-targeting strategies, such as probiotics and prebiotics, antibiotics, fecal microbiota transplantation and physical activity, which could be effective adjuvant therapies developed in order to improve anticancer therapeutic efficiency.
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Hertel, Johannes, Daniel Fässler, Almut Heinken, Frank Weiß, Malte Rühlemann, Corinna Bang, Andre Franke, et al. "NMR Metabolomics Reveal Urine Markers of Microbiome Diversity and Identify Benzoate Metabolism as a Mediator between High Microbial Alpha Diversity and Metabolic Health." Metabolites 12, no. 4 (March 31, 2022): 308. http://dx.doi.org/10.3390/metabo12040308.
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Microbial metabolites measured using NMR may serve as markers for physiological or pathological host–microbe interactions and possibly mediate the beneficial effects of microbiome diversity. Yet, comprehensive analyses of gut microbiome data and the urine NMR metabolome from large general population cohorts are missing. Here, we report the associations between gut microbiota abundances or metrics of alpha diversity, quantified from stool samples using 16S rRNA gene sequencing, with targeted urine NMR metabolites measures from 951 participants of the Study of Health in Pomerania (SHIP). We detected significant genus–metabolite associations for hippurate, succinate, indoxyl sulfate, and formate. Moreover, while replicating the previously reported association between hippurate and measures of alpha diversity, we identified formate and 4-hydroxyphenylacetate as novel markers of gut microbiome alpha diversity. Next, we predicted the urinary concentrations of each metabolite using genus abundances via an elastic net regression methodology. We found profound associations of the microbiome-based hippurate prediction score with markers of liver injury, inflammation, and metabolic health. Moreover, the microbiome-based prediction score for hippurate completely mediated the clinical association pattern of microbial diversity, hinting at a role of benzoate metabolism underlying the positive associations between high alpha diversity and healthy states. In conclusion, large-scale NMR urine metabolomics delivered novel insights into metabolic host–microbiome interactions, identifying pathways of benzoate metabolism as relevant candidates mediating the beneficial health effects of high microbial alpha diversity.
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Lim, Joe Jongpyo, Xueshu Li, Hans-Joachim Lehmler, Dongfang Wang, Haiwei Gu, and Julia Yue Cui. "Gut Microbiome Critically Impacts PCB-induced Changes in Metabolic Fingerprints and the Hepatic Transcriptome in Mice." Toxicological Sciences 177, no. 1 (June 16, 2020): 168–87. http://dx.doi.org/10.1093/toxsci/kfaa090.
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Abstract Polychlorinated biphenyls (PCBs) are ubiquitously detected and have been linked to metabolic diseases. Gut microbiome is recognized as a critical regulator of disease susceptibility; however, little is known how PCBs and gut microbiome interact to modulate hepatic xenobiotic and intermediary metabolism. We hypothesized the gut microbiome regulates PCB-mediated changes in the metabolic fingerprints and hepatic transcriptome. Ninety-day-old female conventional and germ-free mice were orally exposed to the Fox River Mixture (synthetic PCB mixture, 6 or 30 mg/kg) or corn oil (vehicle control, 10 ml/kg), once daily for 3 consecutive days. RNA-seq was conducted in liver, and endogenous metabolites were measured in liver and serum by LC-MS. Prototypical target genes of aryl hydrocarbon receptor, pregnane X receptor, and constitutive androstane receptor were more readily upregulated by PCBs in conventional conditions, indicating PCBs, to the hepatic transcriptome, act partly through the gut microbiome. In a gut microbiome-dependent manner, xenobiotic, and steroid metabolism pathways were upregulated, whereas response to misfolded proteins-related pathways was downregulated by PCBs. At the high PCB dose, NADP, and arginine appear to interact with drug-metabolizing enzymes (ie, Cyp1–3 family), which are highly correlated with Ruminiclostridium and Roseburia, providing a novel explanation of gut-liver interaction from PCB-exposure. Utilizing the Library of Integrated Network-based Cellular Signatures L1000 database, therapeutics targeting anti-inflammatory and endoplasmic reticulum stress pathways are predicted to be remedies that can mitigate PCB toxicity. Our findings demonstrate that habitation of the gut microbiota drives PCB-mediated hepatic responses. Our study adds knowledge of physiological response differences from PCB exposure and considerations for further investigations for gut microbiome-dependent therapeutics.
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Connelly, Sheila, Christian Furlan-Freguia, Brian Fanelli, Nur A. Hasan, Rita R. Colwell, and Michael Kaleko. "673. Novel Delayed-Release Formulation of an Oral β-Lactamase Prevents Gut Microbiome Damage and Attenuates Antibiotic Resistance Caused by Oral Amoxicillin/Clavulanate without Interfering with Amoxicillin Systemic Absorption in Dogs." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S307. http://dx.doi.org/10.1093/ofid/ofz360.741.
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Abstract Background Exposure of the gut microbiota to antibiotics can alter the composition of the microbiome and lead to the emergence and spread of antibiotic resistance. SYN-004 (ribaxamase) is a clinical-stage β-lactamase intended to degrade certain IV β-lactam antibiotics in the GI tract to preserve the gut microbiome. In a phase 2b clinical study, ribaxamase significantly reduced C. difficile infection in patients treated with IV ceftriaxone. A new delayed-release ribaxamase formulation, SYN-007, intended for use with oral β-lactams, was evaluated in dogs that received oral amoxicillin plus the β-lactamase inhibitor, clavulanate (amox/clav). Methods SYN-007 was engineered for release in the lower small intestine, distal to the site of antibiotic absorption. Dogs received amox/clav (40 mg/kg amox/5.7 mg/kg clav, PO, TID) +/- SYN-007 (10 mg, PO, TID) for 16 doses. Amoxicillin serum levels were measured by LC/MS/MS after the first and last doses. DNA, isolated from feces collected before and after antibiotic treatment, was analyzed by whole-genome shotgun sequencing using CosmosID, Inc. metagenomics software. Results Serum amoxicillin levels were not significantly different +/- SYN-007 after the first and last doses of amox/clav. Microbiome analyses revealed that amox/clav disrupted the gut microbiome resulting in loss of some species and overgrowth of other taxa. SYN-007 attenuated changes to gut microbiome composition. Amox/clav exposure resulted in the emergence of many, mainly TEM β-lactamase genes that was reduced with SYN-007. Conclusion Oral amox/clav disrupted the gut microbiome in dogs and resulted in the emergence of β-lactamase genes. SYN-007 diminished amox/clav-mediated microbiome disruption and attenuated emergence of β-lactamase genes. SYN-007 did not interfere with amox systemic absorption indicating that the β-lactamase was not released in the upper small intestine, the site of oral amoxicillin absorption. Antibiotic inactivation represents a potential new treatment paradigm for preservation of the gut microbiome and reduction of antibiotic resistance. SYN-007 has the potential to expand β-lactamase-mediated microbiome protection to oral as well as IV β-lactam antibiotics. Disclosures All authors: No reported disclosures.
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Pero, Brancaccio, Laneri, Biasi, Lombardo, and Scudiero. "A Novel View of Human Helicobacter pylori Infections: Interplay between Microbiota and Beta-Defensins." Biomolecules 9, no. 6 (June 18, 2019): 237. http://dx.doi.org/10.3390/biom9060237.
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The gut microbiota is significantly involved in the preservation of the immune system of the host, protecting it against the pathogenic bacteria of the stomach. The correlation between gut microbiota and the host response supports human gastric homeostasis. Gut microbes may be shifted in Helicobacter pylori (Hp)-infected individuals to advance gastric inflammation and distinguished diseases. Particularly interesting is the establishment of cooperation between gut microbiota and antimicrobial peptides (AMPs) of the host in the gastrointestinal tract. AMPs have great importance in the innate immune reactions to Hp and participate in conservative co-evolution with an intricate microbiome. β-Defensins, a class of short, cationic, arginine-rich proteins belonging to the AMP group, are produced by epithelial and immunological cells. Their expression is enhanced during Hp infection. In this review, we discuss the impact of the gut microbiome on the host response, with particular regard to β-defensins in Hp-associated infections. In microbial infections, mostly in precancerous lesions induced by Hp infection, these modifications could lead to different outcomes.
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Segal, Jonathan P., Joyce W. Y. Mak, Benjamin H. Mullish, James L. Alexander, Siew C. Ng, and Julian R. Marchesi. "The gut microbiome: an under-recognised contributor to the COVID-19 pandemic?" Therapeutic Advances in Gastroenterology 13 (January 2020): 175628482097491. http://dx.doi.org/10.1177/1756284820974914.
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The novel coronavirus infection (COVID-19) caused by the SARS-CoV-2 virus has spread rapidly across the globe, culminating in major global morbidity and mortality. As such, there has been a rapid escalation in scientific and clinical activity aimed at increasing our comprehension of this virus. This volume of work has led to early insights into risk factors associated with severity of disease, and mechanisms that underpin the virulence and dynamics involved in viral transmission. These insights ultimately may help guide potential therapeutics to reduce the human, economic and social impact of this pandemic. Importantly, the gastrointestinal (GI) tract has emerged as an important organ influencing propensity to, and potentially severity of, COVID-19 infection. Furthermore, the gut microbiome has been linked to a variety of risk factors for COVID-19 infection, and manipulation of the gut microbiome is an attractive potential therapeutic target for a number of diseases. While data profiling the gut microbiome in COVID-19 infection to date are limited, they support the possibility of several routes of interaction between COVID-19, the gut microbiome, angiotensin converting enzyme 2 (ACE-2) expression in the small bowel and colon and gut inflammation. This article will explore the evidence that implicates the gut microbiome as a contributing factor to the pathogenesis, severity and disease course of COVID-19, and speculate about the gut microbiome’s capability as a therapeutic avenue against COVID-19. Lay summary It has been noted that certain baseline gut profiles of COVID-19 patients are associated with a more severe disease course, and the gut microbiome impacts the disease course of several contributory risk factors to the severity of COVID-19. A protein called ACE-2, which is found in the small intestine among other sites, is a key receptor for COVID-19 virus entry; there is evidence that the gut microbiome influences ACE-2 receptor expression, and hence may play a role in influencing COVID-19 infectivity and disease severity. Furthermore, the gut microbiome plays a significant role in immune regulation, and hence may be pivotal in influencing the immune response to COVID-19. In terms of understanding COVID-19 treatments, the gut microbiome is known to interact with several drug classes being used to target COVID-19 and should be factored into our understanding of how patients respond to treatment. Importantly, our understanding of the role of the gut microbiome in COVID-19 infection remains in its infancy, but future research may potentially aid our mechanistic understanding of viral infection, and new ways in which we might approach treating it.
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Meneghini, Luigi F. "Metabolic Disturbances and the Intestinal Microbiome." US Endocrinology 11, no. 01 (2015): 34. http://dx.doi.org/10.17925/use.2015.11.1.34.
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The gut microbiome, which can be affected by dietary and other environmental conditions, appears to have an important role in health and disease. A better understanding of the impact of changes in our gut microflora, as well as the determinants of these changes, represents an opportunity to address a number of acute and chronic disease conditions through novel mechanisms and therapeutic approaches.
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Li, Xiang, Tao Zhou, Hao Ma, George Bray, Frank Sacks, and Lu Qi. "Genetically Determined Gut Microbiome Abundance and 2-Year Changes in Central Adiposity and Body Composition: The POUNDS Lost Trial." Current Developments in Nutrition 5, Supplement_2 (June 2021): 1055. http://dx.doi.org/10.1093/cdn/nzab053_048.
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Abstract Objectives Growing evidence has linked gut microbiome abundance with adiposity regulation. A recent genome-wide association study (GWAS) identified 20 genetic variants related to gut microbiome abundance. We aimed to examine whether the genetically determined gut microbiome abundance was associated with 2-year changes in adiposity and body composition among overweight and obese individuals in weight-loss diet interventions. Methods The study included 692 overweight and obese participants from Preventing Overweight Using Novel Dietary Strategies trial (POUNDS Lost). We created a genetic risk score (GRS) for gut microbiome abundance using 20 single nucleotide polymorphisms identified from the most recent GWAS. A higher GRS indicates a higher gut microbiome abundance. Body composition was assessed using dual-energy X-ray absorptiometry (DXA). Results We found that the gut microbiome abundance GRS was significantly associated with waist circumference and body composition during a 2-year diet intervention. Participants with a higher genetically determined gut microbiome abundance had a greater reduction in waist circumference, whole body total fat %, and trunk fat %, and greater increase in lean mass % at 2 years, after adjustment for age, race, sex, body mass index, diet intervention, and baseline values of respective outcome traits (P < 0.05 for all). Least square means comparing the extreme tertiles (T3 vs. T1) were −6.6 vs. −4.4 cm for waist circumference, −3.0 vs. −1.4 for whole-body fat %, 3.0 vs. 1.4 for lean mass %, and −3.9 vs. −1.8 for trunk fat %, respectively. Conclusions The higher genetically determined gut microbiome abundance is related to long-term improvement of whole-body and central fatness, as well as lean body mass in response to low-calorie diet interventions. Funding Sources The study was supported by grants from the National Heart, Lung, and Blood Institute (HL071981, HL034594, HL126024), the National Institute of Diabetes and Digestive and Kidney Diseases (DK115679, DK091718, DK100383), the Fogarty International Center (TW010790), and Tulane Research Centers of Excellence Awards. Xiang Li was the recipient of the American Heart Association Predoctoral Fellowship Award (19PRE34380036).
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Kovács, Tünde, Edit Mikó, Gyula Ujlaki, Heba Yousef, Viktória Csontos, Karen Uray, and Peter Bai. "The involvement of oncobiosis and bacterial metabolite signaling in metastasis formation in breast cancer." Cancer and Metastasis Reviews 40, no. 4 (December 2021): 1223–49. http://dx.doi.org/10.1007/s10555-021-10013-3.
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AbstractBreast cancer, the most frequent cancer in women, is characterized by pathological changes to the microbiome of breast tissue, the tumor, the gut, and the urinary tract. Changes to the microbiome are determined by the stage, grade, origin (NST/lobular), and receptor status of the tumor. This year is the 50th anniversary of when Hill and colleagues first showed that changes to the gut microbiome can support breast cancer growth, namely that the oncobiome can reactivate excreted estrogens. The currently available human and murine data suggest that oncobiosis is not a cause of breast cancer, but can support its growth. Furthermore, preexisting dysbiosis and the predisposition to cancer are transplantable. The breast’s and breast cancer’s inherent microbiome and the gut microbiome promote breast cancer growth by reactivating estrogens, rearranging cancer cell metabolism, bringing about a more inflammatory microenvironment, and reducing the number of tumor-infiltrating lymphocytes. Furthermore, the gut microbiome can produce cytostatic metabolites, the production of which decreases or blunts breast cancer. The role of oncobiosis in the urinary tract is largely uncharted. Oncobiosis in breast cancer supports invasion, metastasis, and recurrence by supporting cellular movement, epithelial-to-mesenchymal transition, cancer stem cell function, and diapedesis. Finally, the oncobiome can modify the pharmacokinetics of chemotherapeutic drugs. The microbiome provides novel leverage on breast cancer that should be exploited for better management of the disease.