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Science (New York, N.Y.) Oct 2011Diet strongly affects human health, partly by modulating gut microbiome composition. We used diet inventories and 16S rDNA sequencing to characterize fecal samples from... (Randomized Controlled Trial)
Randomized Controlled Trial
Diet strongly affects human health, partly by modulating gut microbiome composition. We used diet inventories and 16S rDNA sequencing to characterize fecal samples from 98 individuals. Fecal communities clustered into enterotypes distinguished primarily by levels of Bacteroides and Prevotella. Enterotypes were strongly associated with long-term diets, particularly protein and animal fat (Bacteroides) versus carbohydrates (Prevotella). A controlled-feeding study of 10 subjects showed that microbiome composition changed detectably within 24 hours of initiating a high-fat/low-fiber or low-fat/high-fiber diet, but that enterotype identity remained stable during the 10-day study. Thus, alternative enterotype states are associated with long-term diet.
Topics: Adolescent; Adult; Bacteria; Bacteroides; Child; Child, Preschool; Cross-Sectional Studies; Diet; Dietary Carbohydrates; Dietary Fats; Dietary Fiber; Feces; Gastrointestinal Tract; Humans; Metagenome; Middle Aged; Prevotella; Ruminococcus; Time Factors; Young Adult
PubMed: 21885731
DOI: 10.1126/science.1208344 -
Microbiome Feb 2017Recently, the potential role of gut microbiome in metabolic diseases has been revealed, especially in cardiovascular diseases. Hypertension is one of the most prevalent...
BACKGROUND
Recently, the potential role of gut microbiome in metabolic diseases has been revealed, especially in cardiovascular diseases. Hypertension is one of the most prevalent cardiovascular diseases worldwide, yet whether gut microbiota dysbiosis participates in the development of hypertension remains largely unknown. To investigate this issue, we carried out comprehensive metagenomic and metabolomic analyses in a cohort of 41 healthy controls, 56 subjects with pre-hypertension, 99 individuals with primary hypertension, and performed fecal microbiota transplantation from patients to germ-free mice.
RESULTS
Compared to the healthy controls, we found dramatically decreased microbial richness and diversity, Prevotella-dominated gut enterotype, distinct metagenomic composition with reduced bacteria associated with healthy status and overgrowth of bacteria such as Prevotella and Klebsiella, and disease-linked microbial function in both pre-hypertensive and hypertensive populations. Unexpectedly, the microbiome characteristic in pre-hypertension group was quite similar to that in hypertension. The metabolism changes of host with pre-hypertension or hypertension were identified to be closely linked to gut microbiome dysbiosis. And a disease classifier based on microbiota and metabolites was constructed to discriminate pre-hypertensive and hypertensive individuals from controls accurately. Furthermore, by fecal transplantation from hypertensive human donors to germ-free mice, elevated blood pressure was observed to be transferrable through microbiota, and the direct influence of gut microbiota on blood pressure of the host was demonstrated.
CONCLUSIONS
Overall, our results describe a novel causal role of aberrant gut microbiota in contributing to the pathogenesis of hypertension. And the significance of early intervention for pre-hypertension was emphasized.
Topics: Animals; Blood Pressure; Cohort Studies; Dysbiosis; Essential Hypertension; Fecal Microbiota Transplantation; Gastrointestinal Microbiome; Gastrointestinal Tract; Germ-Free Life; Humans; Hypertension; Klebsiella; Male; Mice; Mice, Inbred C57BL; Prehypertension; Prevotella; Prospective Studies
PubMed: 28143587
DOI: 10.1186/s40168-016-0222-x -
Nature Medicine Feb 2021The gut microbiome is shaped by diet and influences host metabolism; however, these links are complex and can be unique to each individual. We performed deep metagenomic... (Clinical Trial)
Clinical Trial
The gut microbiome is shaped by diet and influences host metabolism; however, these links are complex and can be unique to each individual. We performed deep metagenomic sequencing of 1,203 gut microbiomes from 1,098 individuals enrolled in the Personalised Responses to Dietary Composition Trial (PREDICT 1) study, whose detailed long-term diet information, as well as hundreds of fasting and same-meal postprandial cardiometabolic blood marker measurements were available. We found many significant associations between microbes and specific nutrients, foods, food groups and general dietary indices, which were driven especially by the presence and diversity of healthy and plant-based foods. Microbial biomarkers of obesity were reproducible across external publicly available cohorts and in agreement with circulating blood metabolites that are indicators of cardiovascular disease risk. While some microbes, such as Prevotella copri and Blastocystis spp., were indicators of favorable postprandial glucose metabolism, overall microbiome composition was predictive for a large panel of cardiometabolic blood markers including fasting and postprandial glycemic, lipemic and inflammatory indices. The panel of intestinal species associated with healthy dietary habits overlapped with those associated with favorable cardiometabolic and postprandial markers, indicating that our large-scale resource can potentially stratify the gut microbiome into generalizable health levels in individuals without clinically manifest disease.
Topics: Adult; Biomarkers; Blastocystis; Blood Glucose; Child; Diet; Fasting; Feeding Behavior; Female; Food Microbiology; Gastrointestinal Microbiome; Glucose; High-Throughput Nucleotide Sequencing; Humans; Male; Metagenome; Microbiota; Middle Aged; Obesity; Postprandial Period; Prevotella
PubMed: 33432175
DOI: 10.1038/s41591-020-01183-8 -
International Journal of Molecular... Nov 2022There is a growing body of evidence highlighting there are significant changes in the gut microbiota composition and relative abundance in various neurological... (Review)
Review
There is a growing body of evidence highlighting there are significant changes in the gut microbiota composition and relative abundance in various neurological disorders. We performed a systematic review of the different microbiota altered in a wide range of neurological disorders (Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis, and stroke). Fifty-two studies were included representing 5496 patients. At the genus level, the most frequently involved microbiota are Akkermansia, Faecalibacterium, and Prevotella. The overlap between the pathologies was strongest for MS and PD, sharing eight genera (Akkermansia, Butyricicoccus, Bifidobacterium, Coprococcus, Dorea, Faecalibacterium, Parabacteroides, and Prevotella) and PD and stroke, sharing six genera (Enterococcus, Faecalibacterium, Lactobacillus, Parabacteroides, Prevotella, and Roseburia). The identification signatures overlapping for AD, PD, and MS raise the question of whether these reflect a common etiology or rather common consequence of these diseases. The interpretation is hampered by the low number and low power for AD, ALS, and stroke with ample opportunity for false positive and false negative findings.
Topics: Humans; Gastrointestinal Microbiome; Nervous System Diseases; Parkinson Disease; Microbiota; Akkermansia; Multiple Sclerosis; Prevotella; Clostridiaceae; Clostridiales; Stroke
PubMed: 36430144
DOI: 10.3390/ijms232213665 -
Immunology Aug 2017The microbiota plays a central role in human health and disease by shaping immune development, immune responses and metabolism, and by protecting from invading... (Review)
Review
The microbiota plays a central role in human health and disease by shaping immune development, immune responses and metabolism, and by protecting from invading pathogens. Technical advances that allow comprehensive characterization of microbial communities by genetic sequencing have sparked the hunt for disease-modulating bacteria. Emerging studies in humans have linked the increased abundance of Prevotella species at mucosal sites to localized and systemic disease, including periodontitis, bacterial vaginosis, rheumatoid arthritis, metabolic disorders and low-grade systemic inflammation. Intriguingly, Prevotella abundance is reduced within the lung microbiota of patients with asthma and chronic obstructive pulmonary disease. Increased Prevotella abundance is associated with augmented T helper type 17 (Th17) -mediated mucosal inflammation, which is in line with the marked capacity of Prevotella in driving Th17 immune responses in vitro. Studies indicate that Prevotella predominantly activate Toll-like receptor 2, leading to production of Th17-polarizing cytokines by antigen-presenting cells, including interleukin-23 (IL-23) and IL-1. Furthermore, Prevotella stimulate epithelial cells to produce IL-8, IL-6 and CCL20, which can promote mucosal Th17 immune responses and neutrophil recruitment. Prevotella-mediated mucosal inflammation leads to systemic dissemination of inflammatory mediators, bacteria and bacterial products, which in turn may affect systemic disease outcomes. Studies in mice support a causal role of Prevotella as colonization experiments promote clinical and inflammatory features of human disease. When compared with strict commensal bacteria, Prevotella exhibit increased inflammatory properties, as demonstrated by augmented release of inflammatory mediators from immune cells and various stromal cells. These findings indicate that some Prevotella strains may be clinically important pathobionts that can participate in human disease by promoting chronic inflammation.
Topics: Animals; Bacteroidaceae Infections; Chronic Disease; Cytokines; High-Throughput Nucleotide Sequencing; Humans; Immunity; Immunomodulation; Inflammation; Intestinal Mucosa; Microbiota; Prevotella; Th17 Cells; Toll-Like Receptor 2
PubMed: 28542929
DOI: 10.1111/imm.12760 -
Scientific Reports Apr 2019Many studies have reported abnormal gut microbiota in individuals with Autism Spectrum Disorders (ASD), suggesting a link between gut microbiome and autism-like... (Clinical Trial)
Clinical Trial
Many studies have reported abnormal gut microbiota in individuals with Autism Spectrum Disorders (ASD), suggesting a link between gut microbiome and autism-like behaviors. Modifying the gut microbiome is a potential route to improve gastrointestinal (GI) and behavioral symptoms in children with ASD, and fecal microbiota transplant could transform the dysbiotic gut microbiome toward a healthy one by delivering a large number of commensal microbes from a healthy donor. We previously performed an open-label trial of Microbiota Transfer Therapy (MTT) that combined antibiotics, a bowel cleanse, a stomach-acid suppressant, and fecal microbiota transplant, and observed significant improvements in GI symptoms, autism-related symptoms, and gut microbiota. Here, we report on a follow-up with the same 18 participants two years after treatment was completed. Notably, most improvements in GI symptoms were maintained, and autism-related symptoms improved even more after the end of treatment. Important changes in gut microbiota at the end of treatment remained at follow-up, including significant increases in bacterial diversity and relative abundances of Bifidobacteria and Prevotella. Our observations demonstrate the long-term safety and efficacy of MTT as a potential therapy to treat children with ASD who have GI problems, and warrant a double-blind, placebo-controlled trial in the future.
Topics: Autistic Disorder; Bifidobacterium; Child; Dysbiosis; Fecal Microbiota Transplantation; Female; Follow-Up Studies; Gastrointestinal Diseases; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Male; Prevotella
PubMed: 30967657
DOI: 10.1038/s41598-019-42183-0 -
Cell Nov 2018Many US immigrant populations develop metabolic diseases post immigration, but the causes are not well understood. Although the microbiome plays a role in metabolic...
Many US immigrant populations develop metabolic diseases post immigration, but the causes are not well understood. Although the microbiome plays a role in metabolic disease, there have been no studies measuring the effects of US immigration on the gut microbiome. We collected stool, dietary recalls, and anthropometrics from 514 Hmong and Karen individuals living in Thailand and the United States, including first- and second-generation immigrants and 19 Karen individuals sampled before and after immigration, as well as from 36 US-born European American individuals. Using 16S and deep shotgun metagenomic DNA sequencing, we found that migration from a non-Western country to the United States is associated with immediate loss of gut microbiome diversity and function in which US-associated strains and functions displace native strains and functions. These effects increase with duration of US residence and are compounded by obesity and across generations.
Topics: Adult; Asian People; Bacteroides; Dietary Fiber; Emigrants and Immigrants; Emigration and Immigration; Gastrointestinal Microbiome; Humans; Metagenome; Obesity; Prevotella; United States
PubMed: 30388453
DOI: 10.1016/j.cell.2018.10.029 -
Cellular & Molecular Immunology Dec 2022Both preclinical and established rheumatoid arthritis (RA) patients display alterations in the gut microbiome. Prevotella spp. are preferentially enriched in a subset of...
Both preclinical and established rheumatoid arthritis (RA) patients display alterations in the gut microbiome. Prevotella spp. are preferentially enriched in a subset of RA patients. Here, we isolated a Prevotella strain, P. copri RA, from the feces of RA patients and showed that colonization of P. copri RA exacerbated arthritis in a collagen-induced arthritis (CIA) model. With the presence of P. copri RA colonization, a high-fiber diet exacerbated arthritis via microbial alterations and intestinal inflammation. Colonization of P. copri together with a high-fiber diet enabled the digestion of complex fiber, which led to the overproduction of organic acids, including fumarate, succinate and short-chain fatty acids. Succinate promoted proinflammatory responses in macrophages, and supplementation with succinate exacerbated arthritis in the CIA model. Our findings highlight the importance of dysbiosis when evaluating the effects of dietary interventions on RA pathogenesis and provide new insight into dietary interventions or microbiome modifications to improve RA management.
Topics: Animals; Humans; Prevotella; Arthritis, Rheumatoid; Arthritis, Experimental; Diet; Succinates
PubMed: 36323929
DOI: 10.1038/s41423-022-00934-6 -
Cell Host & Microbe Oct 2019The human gut contains a vast array of viruses, mostly bacteriophages. The majority remain uncharacterized, and their roles in shaping the gut microbiome and in...
The human gut contains a vast array of viruses, mostly bacteriophages. The majority remain uncharacterized, and their roles in shaping the gut microbiome and in impacting on human health remain poorly understood. We performed longitudinal metagenomic analysis of fecal viruses in healthy adults that reveal high temporal stability, individual specificity, and correlation with the bacterial microbiome. Using a database-independent approach that uses most of the sequencing data, we uncovered the existence of a stable, numerically predominant individual-specific persistent personal virome. Clustering of viral genomes and de novo taxonomic annotation identified several groups of crAss-like and Microviridae bacteriophages as the most stable colonizers of the human gut. CRISPR-based host prediction highlighted connections between these stable viral communities and highly predominant gut bacterial taxa such as Bacteroides, Prevotella, and Faecalibacterium. This study provides insights into the structure of the human gut virome and serves as an important baseline for hypothesis-driven research.
Topics: Bacteroides; Faecalibacterium; Gastrointestinal Microbiome; Humans; Longitudinal Studies; Metagenome; Microviridae; Prevotella; Viral Load
PubMed: 31600503
DOI: 10.1016/j.chom.2019.09.009 -
Microbiome Aug 2021Excessive fat accumulation of pigs is undesirable, as it severely affects economic returns in the modern pig industry. Studies in humans and mice have examined the role...
BACKGROUND
Excessive fat accumulation of pigs is undesirable, as it severely affects economic returns in the modern pig industry. Studies in humans and mice have examined the role of the gut microbiome in host energy metabolism. Commercial Duroc pigs are often fed formula diets with high energy and protein contents. Whether and how the gut microbiome under this type of diet regulates swine fat accumulation is largely unknown.
RESULTS
In the present study, we systematically investigated the correlation of gut microbiome with pig lean meat percentage (LMP) in 698 commercial Duroc pigs and found that Prevotella copri was significantly associated with fat accumulation of pigs. Fat pigs had significantly higher abundance of P. copri in the gut. High abundance of P. copri was correlated with increased concentrations of serum metabolites associated with obesity, e.g., lipopolysaccharides, branched chain amino acids, aromatic amino acids, and the metabolites of arachidonic acid. Host intestinal barrier permeability and chronic inflammation response were increased. A gavage experiment using germ-free mice confirmed that the P. copri isolated from experimental pigs was a causal species increasing host fat accumulation and altering serum metabolites. Colon, adipose tissue, and muscle transcriptomes in P. copri-gavaged mice indicated that P. copri colonization activated host chronic inflammatory responses through the TLR4 and mTOR signaling pathways and significantly upregulated the expression of the genes related to lipogenesis and fat accumulation, but attenuated the genes associated with lipolysis, lipid transport, and muscle growth.
CONCLUSIONS
Taken together, the results proposed that P. copri in the gut microbial communities of pigs fed with commercial formula diets activates host chronic inflammatory responses by the metabolites through the TLR4 and mTOR signaling pathways, and increases host fat deposition significantly. The results provide fundamental knowledge for reducing fat accumulation in pigs through regulating the gut microbial composition. Video Abstract.
Topics: Animals; Diet; Gastrointestinal Microbiome; Mice; Obesity; Prevotella; Swine
PubMed: 34419147
DOI: 10.1186/s40168-021-01110-0