-
Nature Jan 2014Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut, but it remains unclear how rapidly and... (Clinical Trial)
Clinical Trial
Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut, but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals, reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids and the outgrowth of microorganisms capable of triggering inflammatory bowel disease. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles.
Topics: Adult; Bacteria; Bacteroides; Bile Acids and Salts; Bilophila; Carnivory; Diet; Diet, Vegetarian; Dietary Fats; Feces; Female; Fermentation; Food Microbiology; Gastrointestinal Tract; Gene Expression Regulation, Bacterial; Herbivory; Humans; Inflammatory Bowel Diseases; Male; Metagenome; Microbiota; Time Factors; Young Adult
PubMed: 24336217
DOI: 10.1038/nature12820 -
Disease Markers 2022To systematically evaluate the differences in intestinal flora before and after menopause. To provide a possible mechanism for perimenopausal syndrome and provide a... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To systematically evaluate the differences in intestinal flora before and after menopause. To provide a possible mechanism for perimenopausal syndrome and provide a basis for probiotics as adjuvant therapy.
METHODS
MEDLINE, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), CNKI, Wanfang, and VIP databases were searched. The included studies were case-control studies.
RESULTS
Three case-control studies were included, with a total of 156 people. At the phylum level, there were no differences between premenopausal and postmenopausal women. At the genus level, the relative abundances of A. odoratum and B. cholerae were higher in postmenopausal women than in premenopausal women, with no differences among other genera. The Shannon diversity index increased after menopause, but no differences were found. Only one study found a positive association of estradiol with Gammaproteobacteria and Myxococcales and a negative association with Prevotellaceae.
CONCLUSIONS
On the basis of previous studies, it was found that there was no significant difference at the phylum level between postmenopausal women and premenopausal women, but Odoribacter and Bilophila increased at the genus level in postmenopausal women. The class of Gammaproteobacteria may be positively correlated with estradiol. Limited by the number of included studies, more high-quality clinical studies are needed for validation.
Topics: Estradiol; Female; Gastrointestinal Microbiome; Humans; Menopause; Postmenopause; Premenopause
PubMed: 35923245
DOI: 10.1155/2022/3767373 -
Journal of Biomedical Science Mar 2021Previous study disclosed Fucosyltransferase 2 (Fut2) gene as a IBD risk locus. This study aimed to explore the mechanism of Fut2 in IBD susceptibility and to propose a...
BACKGROUND AND AIMS
Previous study disclosed Fucosyltransferase 2 (Fut2) gene as a IBD risk locus. This study aimed to explore the mechanism of Fut2 in IBD susceptibility and to propose a new strategy for the treatment of IBD.
METHODS
Intestinal epithelium-specific Fut2 knockout (Fut2) mice was used. Colitis was induced by dextran sulfate sodium (DSS). The composition and diversity of gut microbiota were assessed via 16S rRNA analysis and the metabolomic findings was obtained from mice feces via metabolite profiling. The fecal microbiota transplantation (FMT) experiment was performed to confirm the association of gut microbiota and LPC. WT mice were treated with Lysophosphatidylcholine (LPC) to verify its impact on colitis.
RESULTS
The expression of Fut2 and α-1,2-fucosylation in colonic tissues were decreased in patients with UC (UC vs. control, P = 0.036) and CD (CD vs. control, P = 0.031). When treated with DSS, in comparison to WT mice, more severe intestinal inflammation and destructive barrier functions in Fut2 mice was noted. Lower gut microbiota diversity was observed in Fut2 mice compared with WT mice (p < 0.001). When exposed to DSS, gut bacterial diversity and composition altered obviously in Fut2 mice and the fecal concentration of LPC was increased. FMT experiment revealed that mice received the fecal microbiota from Fut2 mice exhibited more severe colitis and higher fecal LPC concentration. Correlation analysis showed that the concentration of LPC was positively correlated with four bacteria-Escherichia, Bilophila, Enterorhabdus and Gordonibacter. Furthermore, LPC was proved to promote the release of pro-inflammatory cytokines and damage epithelial barrier in vitro and in vivo.
CONCLUSION
Fut2 and α-1,2-fucosylation in colon were decreased not only in CD but also in UC patients. Gut microbiota in Fut2 mice is altered structurally and functionally, promoting generation of LPC which was proved to promote inflammation and damage epithelial barrier.
Topics: Animals; Bacteria; Colitis; Fucosyltransferases; Gastrointestinal Microbiome; Humans; Intestinal Mucosa; Lysophosphatidylcholines; Mice; Mice, Transgenic; Galactoside 2-alpha-L-fucosyltransferase
PubMed: 33722220
DOI: 10.1186/s12929-021-00711-z -
Frontiers in Immunology 2021Several studies have reported alterations in gut microbiota composition of Alzheimer's disease (AD) patients. However, the observed differences are not consistent across...
INTRODUCTION
Several studies have reported alterations in gut microbiota composition of Alzheimer's disease (AD) patients. However, the observed differences are not consistent across studies. We aimed to investigate associations between gut microbiota composition and AD biomarkers using machine learning models in patients with AD dementia, mild cognitive impairment (MCI) and subjective cognitive decline (SCD).
MATERIALS AND METHODS
We included 170 patients from the Amsterdam Dementia Cohort, comprising 33 with AD dementia (66 ± 8 years, 46%F, mini-mental state examination (MMSE) 21[19-24]), 21 with MCI (64 ± 8 years, 43%F, MMSE 27[25-29]) and 116 with SCD (62 ± 8 years, 44%F, MMSE 29[28-30]). Fecal samples were collected and gut microbiome composition was determined using 16S rRNA sequencing. Biomarkers of AD included cerebrospinal fluid (CSF) amyloid-beta 1-42 (amyloid) and phosphorylated tau (p-tau), and MRI visual scores (medial temporal atrophy, global cortical atrophy, white matter hyperintensities). Associations between gut microbiota composition and dichotomized AD biomarkers were assessed with machine learning classification models. The two models with the highest area under the curve (AUC) were selected for logistic regression, to assess associations between the 20 best predicting microbes and the outcome measures from these machine learning models while adjusting for age, sex, BMI, diabetes, medication use, and MMSE.
RESULTS
The machine learning prediction for amyloid and p-tau from microbiota composition performed best with AUCs of 0.64 and 0.63. Highest ranked microbes included several short chain fatty acid (SCFA)-producing species. Higher abundance of and lower abundance of group spp., spp., spp., spp., spp., , and spp., was associated with higher odds of amyloid positivity. We found associations between lower abundance of spp., spp., and and higher odds of positive p-tau status.
CONCLUSIONS
Gut microbiota composition was associated with amyloid and p-tau status. We extend on recent studies that observed associations between SCFA levels and AD CSF biomarkers by showing that lower abundances of SCFA-producing microbes were associated with higher odds of positive amyloid and p-tau status.
Topics: Aged; Alzheimer Disease; Biomarkers; Brain-Gut Axis; Cognitive Dysfunction; Comorbidity; Dementia; Disease Susceptibility; Female; Gastrointestinal Microbiome; Humans; Machine Learning; Male; Middle Aged; Risk Factors
PubMed: 35173707
DOI: 10.3389/fimmu.2021.794519 -
CNS Neuroscience & Therapeutics Jan 2023Recent advances have highlighted the relationships between gut dysbiosis and Parkinson's disease (PD). Microbiota transplantation from PD patients to mice can induce... (Review)
Review
INTRODUCTION
Recent advances have highlighted the relationships between gut dysbiosis and Parkinson's disease (PD). Microbiota transplantation from PD patients to mice can induce increased alpha-synuclein-mediated motor deficits. Human studies have identified differences in the gut microbiota of PD patients compared to healthy controls. We undertook a systematic review to evaluate the available evidence for the involvement of gut bacteria in the etiology of PD.
METHODS
The PubMed databank, the China National Knowledge Infrastructure databank, and Wanfang Data were searched from inception until June 2021 to identify human case-control studies that investigated relationships between PD and microbiota quantified from feces. We evaluated the resulting studies focusing on bacterial taxa that were different between PD patients and healthy controls.
RESULTS
Twenty-six studies were found in which 53 microbial families and 98 genera exhibited differences between patients with PD and healthy controls. The genera identified by more than two studies as increased in PD were Bifidobacterium, Alistipes, Christensenella, Enterococcus, Oscillospira, Bilophila, Desulfovibrio, Escherichia/Shigella, and Akkermansia, while Prevotella, Blautia, Faecalibacterium, Fusicatenibacter, and Haemophilus had three or more reports of being lower in PD patients. More than one report demonstrated that Bacteroides, Odoribacter, Parabacteroides, Butyricicoccus, Butyrivibrio, Clostridium, Coprococcus, Lachnospira, Lactobacillus, Megasphaera, Phascolarctobacterium, Roseburia, Ruminococcus, Streptococcus, and Klebsiella were altered in both directions.
CONCLUSION
Our review shows that the involvement of the gut microbiome in the etiology of PD may involve alterations of short-chain fatty acids (SCFAs)-producing bacteria and an increase in putative gut pathobionts. SCFAs-producing bacteria may vary above or below an "optimal range," causing imbalances. Considering that Bifidobacterium, Lactobacillus, and Akkermansia are beneficial for human health, increased Bifidobacterium and Lactobacillus in the PD gut microbiome may be associated with PD medications, especially COMT inhibitors, while a high level of Akkermansia may be associated with aging.
Topics: Humans; Animals; Mice; Parkinson Disease; Gastrointestinal Microbiome; Bacteria; Feces; Fatty Acids, Volatile
PubMed: 36284437
DOI: 10.1111/cns.13990 -
Microbiome Jul 2022Disease resistance phenotypes are associated with immune regulatory functions and immune tolerance and have implications for both the livestock industry and human...
BACKGROUND
Disease resistance phenotypes are associated with immune regulatory functions and immune tolerance and have implications for both the livestock industry and human health. Microbiota plays an essential role in regulating immunity and autoimmunity in the host organism, but the influence of host-microbiota interactions on disease resistance phenotypes remains unclear. Here, multiomics analysis was performed to identify potential regulatory mechanisms of disease resistance at both the microbiome and host levels in two pig breeds.
RESULTS
Acute colitis models were established in Min pigs and Yorkshire pigs, and control and diseased individuals were compared. Compared with Yorkshire pigs under the same nutritional and management conditions, Min pigs exhibited strong disease resistance, as indicated by a low disease activity index (DAI) and a low histological activity index (HAI). Microbiota sequencing analysis showed that potentially harmful microbes Desulfovibrio, Bacteroides and Streptococcus were enriched in diseased individuals of the two breeds. Notably, potentially beneficial microbes, such as Lactobacillus, Clostridia and Eubacterium, and several genera belonging to Ruminococcaceae and Christensenellaceae were enriched in diseased Min pigs and were found to be positively associated with the microbial metabolites related to intestinal barrier function. Specifically, the concentrations of indole derivatives and short-chain fatty acids were increased in diseased Min pigs, suggesting beneficial action in protecting intestinal barrier. In addition, lower concentrations of bile acid metabolites and short-chain fatty acids were observed in diseased Yorkshire pigs, which were associated with increased potentially harmful microbes, such as Bilophila and Alistipes. Concerning enrichment of the immune response, the increase in CD4 T cells in the lamina propria improved supervision of the host immunity response in diseased Min pigs, contributing to the maintenance of Th2-type immune superiority and immune tolerance patterns and control of excessive inflammation with the help of potentially beneficial microbes. In diseased Yorkshire pigs, more terms belonging to biological processes of immunity were enriched, including Toll-like receptors signalling, NF-κB signalling and Th1 and Th17-type immune responses, along with the increases of potentially harmful microbes and damaged intestinal barrier.
CONCLUSIONS
Cumulatively, the results for the two pig breeds highlight that host-microbiota crosstalk promotes a disease resistance phenotype in three ways: by maintaining partial PRR nonactivation, maintaining Th2-type immune superiority and immunological tolerance patterns and recovering gut barrier function to protect against colonic diseases. Video abstract.
Topics: Animals; Colitis; Disease Resistance; Gastrointestinal Microbiome; Humans; Inflammatory Bowel Diseases; Microbiota; Swine
PubMed: 35907917
DOI: 10.1186/s40168-022-01303-1 -
Frontiers in Cardiovascular Medicine 2023The pathogenesis of hypertension involves a diverse range of genetic, environmental, hemodynamic, and more causative factors. Recent evidence points to an association...
BACKGROUND & AIMS
The pathogenesis of hypertension involves a diverse range of genetic, environmental, hemodynamic, and more causative factors. Recent evidence points to an association between the gut microbiome and hypertension. Given that the microbiota is in part determined by host genetics, we used the two-sample Mendelian randomization (MR) analysis to address the bidirectional causal link between gut microbiota and hypertension.
METHODS
We selected genetic variants ( < 1 × 10) for gut microbiota ( = 18,340) from the MiBioGen study. Genetic association estimates for hypertension were extracted from genome-wide association study (GWAS) summary statistics on 54,358 cases and 408,652 controls. Seven complementary MR methods were implemented, including the inverse-variance weighted (IVW) method, followed by sensitivity analyses to verify the robustness of the results. Reverse-direction MR analyses were further conducted to probe if there was a reverse causative relationship. Bidirectional MR analysis then examines a modulation of gut microbiota composition by hypertension.
RESULTS
At the genus level, our MR estimates from gut microbiome to hypertension showed that there were 5 protective factors , , , and (id.1000000073), while 6 genera , , , , , and (id.2041) are risk factors. The and were detrimental and beneficial at the family level, respectively. In contrast, the MR results of hypertension-gut flora showed hypertensive states can lead to an increased abundance of E, , and and a lower abundance of , , , and .
CONCLUSION
Altered gut microbiota is a causal factor in the development of hypertension, and hypertension causes imbalances in the intestinal flora. Substantial research is still needed to find the key gut flora and explore the specific mechanisms of their effects so that new biomarkers can be found for blood pressure control.
PubMed: 37215554
DOI: 10.3389/fcvm.2023.1167346 -
Gut Nov 2017Contrary to the long-standing prerequisite of inducing selective (ie, bifidogenic) effects, recent findings suggest that prebiotic interventions lead to ecosystem-wide... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Contrary to the long-standing prerequisite of inducing selective (ie, bifidogenic) effects, recent findings suggest that prebiotic interventions lead to ecosystem-wide microbiota shifts. Yet, a comprehensive characterisation of this process is still lacking. Here, we apply 16S rDNA microbiota profiling and matching (gas chromatography mass spectrometry) metabolomics to assess the consequences of inulin fermentation both on the composition of the colon bacterial ecosystem and faecal metabolites profiles.
DESIGN
Faecal samples collected during a double-blind, randomised, cross-over intervention study set up to assess the effect of inulin consumption on stool frequency in healthy adults with mild constipation were analysed. Faecal microbiota composition and metabolite profiles were linked to the study's clinical outcome as well as to quality-of-life measurements recorded.
RESULTS
While faecal metabolite profiles were not significantly altered by inulin consumption, our analyses did detect a modest effect on global microbiota composition and specific inulin-induced changes in relative abundances of , and were identified. The observed decrease in abundances following inulin consumption was associated with both softer stools and a favourable change in constipation-specific quality-of-life measures.
CONCLUSIONS
Ecosystem-wide analysis of the effect of a dietary intervention with prebiotic inulin-type fructans on the colon microbiota revealed that this effect is specifically associated with three genera, one of which () representing a promising novel target for mechanistic research.
TRIAL REGISTRATION NUMBER
NCT02548247.
Topics: Biomarkers; Colon; Constipation; Cross-Over Studies; Double-Blind Method; Feces; Female; Gastrointestinal Microbiome; Humans; Inulin; Male; Metabolome; Prebiotics; Treatment Outcome
PubMed: 28213610
DOI: 10.1136/gutjnl-2016-313271 -
Nature Medicine Nov 2023Genome-wide association studies (GWASs) have provided numerous associations between human single-nucleotide polymorphisms (SNPs) and health traits. Likewise,...
Genome-wide association studies (GWASs) have provided numerous associations between human single-nucleotide polymorphisms (SNPs) and health traits. Likewise, metagenome-wide association studies (MWASs) between bacterial SNPs and human traits can suggest mechanistic links, but very few such studies have been done thus far. In this study, we devised an MWAS framework to detect SNPs and associate them with host phenotypes systematically. We recruited and obtained gut metagenomic samples from a cohort of 7,190 healthy individuals and discovered 1,358 statistically significant associations between a bacterial SNP and host body mass index (BMI), from which we distilled 40 independent associations. Most of these associations were unexplained by diet, medications or physical exercise, and 17 replicated in a geographically independent cohort. We uncovered BMI-associated SNPs in 27 bacterial species, and 12 of them showed no association by standard relative abundance analysis. We revealed a BMI association of an SNP in a potentially inflammatory pathway of Bilophila wadsworthia as well as of a group of SNPs in a region coding for energy metabolism functions in a Faecalibacterium prausnitzii genome. Our results demonstrate the importance of considering nucleotide-level diversity in microbiome studies and pave the way toward improved understanding of interpersonal microbiome differences and their potential health implications.
Topics: Humans; Gastrointestinal Microbiome; Body Mass Index; Polymorphism, Single Nucleotide; Genome-Wide Association Study; Microbiota; Bacteria
PubMed: 37919437
DOI: 10.1038/s41591-023-02599-8 -
Microbiome Feb 2017Autism spectrum disorders (ASDs) are neurodevelopmental conditions characterized by social and behavioural impairments. In addition to neurological symptoms, ASD...
BACKGROUND
Autism spectrum disorders (ASDs) are neurodevelopmental conditions characterized by social and behavioural impairments. In addition to neurological symptoms, ASD subjects frequently suffer from gastrointestinal abnormalities, thus implying a role of the gut microbiota in ASD gastrointestinal pathophysiology.
RESULTS
Here, we characterized the bacterial and fungal gut microbiota in a cohort of autistic individuals demonstrating the presence of an altered microbial community structure. A fraction of 90% of the autistic subjects were classified as severe ASDs. We found a significant increase in the Firmicutes/Bacteroidetes ratio in autistic subjects due to a reduction of the Bacteroidetes relative abundance. At the genus level, we observed a decrease in the relative abundance of Alistipes, Bilophila, Dialister, Parabacteroides, and Veillonella in the ASD cohort, while Collinsella, Corynebacterium, Dorea, and Lactobacillus were significantly increased. Constipation has been then associated with different bacterial patterns in autistic and neurotypical subjects, with constipated autistic individuals characterized by high levels of bacterial taxa belonging to Escherichia/Shigella and Clostridium cluster XVIII. We also observed that the relative abundance of the fungal genus Candida was more than double in the autistic than neurotypical subjects, yet due to a larger dispersion of values, this difference was only partially significant.
CONCLUSIONS
The finding that, besides the bacterial gut microbiota, also the gut mycobiota contributes to the alteration of the intestinal microbial community structure in ASDs opens the possibility for new potential intervention strategies aimed at the relief of gastrointestinal symptoms in ASDs.
Topics: Adolescent; Autism Spectrum Disorder; Bacteria; Child; Child, Preschool; Clostridium; Constipation; Feces; Female; Firmicutes; Fungi; Gastrointestinal Diseases; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Lactobacillus; Male; Mycobiome
PubMed: 28222761
DOI: 10.1186/s40168-017-0242-1