-
Nature Microbiology Feb 2022Ulcerative colitis (UC) is driven by disruptions in host-microbiota homoeostasis, but current treatments exclusively target host inflammatory pathways. To understand how...
Ulcerative colitis (UC) is driven by disruptions in host-microbiota homoeostasis, but current treatments exclusively target host inflammatory pathways. To understand how host-microbiota interactions become disrupted in UC, we collected and analysed six faecal- or serum-based omic datasets (metaproteomic, metabolomic, metagenomic, metapeptidomic and amplicon sequencing profiles of faecal samples and proteomic profiles of serum samples) from 40 UC patients at a single inflammatory bowel disease centre, as well as various clinical, endoscopic and histologic measures of disease activity. A validation cohort of 210 samples (73 UC, 117 Crohn's disease, 20 healthy controls) was collected and analysed separately and independently. Data integration across both cohorts showed that a subset of the clinically active UC patients had an overabundance of proteases that originated from the bacterium Bacteroides vulgatus. To test whether B. vulgatus proteases contribute to UC disease activity, we first profiled B. vulgatus proteases found in patients and bacterial cultures. Use of a broad-spectrum protease inhibitor improved B. vulgatus-induced barrier dysfunction in vitro, and prevented colitis in B. vulgatus monocolonized, IL10-deficient mice. Furthermore, transplantation of faeces from UC patients with a high abundance of B. vulgatus proteases into germfree mice induced colitis dependent on protease activity. These results, stemming from a multi-omics approach, improve understanding of functional microbiota alterations that drive UC and provide a resource for identifying other pathways that could be inhibited as a strategy to treat this disease.
Topics: Adult; Animals; Bacterial Proteins; Bacteroides; Cohort Studies; Colitis, Ulcerative; Feces; Female; Gastrointestinal Microbiome; Humans; Longitudinal Studies; Male; Metagenome; Metagenomics; Mice; Middle Aged; Peptide Hydrolases; Proteomics; Severity of Illness Index
PubMed: 35087228
DOI: 10.1038/s41564-021-01050-3 -
Circulation Nov 2018It is increasingly recognized that gut microbiota play a pivotal role in the development of atherosclerotic cardiovascular disease. Previously, we have reported that the...
BACKGROUND
It is increasingly recognized that gut microbiota play a pivotal role in the development of atherosclerotic cardiovascular disease. Previously, we have reported that the abundance of genus Bacteroides is lower in patients with coronary artery disease (CAD) than in patients without CAD with coronary risk factors or in healthy volunteers. However, it remains unclear which and how specific gut bacteria contribute to the progression of atherosclerosis.
METHODS
We recruited patients with CAD patients and controls without CAD with coronary risk factors. We then compared gut microbial composition using 16S ribosomal RNA gene sequencing in fecal samples to detect species with differential abundance between 2 groups. Subsequently, we used atherosclerosis-prone mice to study the mechanisms underlying the relationship between such species and atherosclerosis.
RESULTS
Human fecal 16S ribosomal RNA gene sequencing revealed a significantly lower abundance of Bacteroides vulgatus and Bacteroides dorei in patients with CAD. This significant differential abundance was confirmed by quantitative polymerase chain reaction. Gavage with live B. vulgatus and B. dorei attenuated atherosclerotic lesion formation in atherosclerosis-prone mice, markedly ameliorating endotoxemia followed by decreasing gut microbial lipopolysaccharide production, effectively suppressing proinflammatory immune responses. Furthermore, fecal lipopolysaccharide levels in patients with CAD were significantly higher and negatively correlated with the abundance of B. vulgatus and B. dorei.
CONCLUSIONS
Our translational research findings identify a previously unknown link between specific gut bacteria and atherosclerosis. Treatment with live B. vulgatus and B. dorei may help prevent CAD.
CLINICAL TRIAL REGISTRATION
URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000018051 . Unique identifier: UMIN000015703.
Topics: Aged; Animals; Atherosclerosis; Bacteroides; Feces; Female; Gastrointestinal Microbiome; Humans; Immunity, Mucosal; Intestines; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; RNA, Ribosomal, 16S; Risk Factors; Sequence Analysis, RNA; Tight Junctions
PubMed: 30571343
DOI: 10.1161/CIRCULATIONAHA.118.033714 -
Nature Communications Oct 2023Although the gut microbiota has been reported to influence osteoporosis risk, the individual species involved, and underlying mechanisms, remain largely unknown. We...
Although the gut microbiota has been reported to influence osteoporosis risk, the individual species involved, and underlying mechanisms, remain largely unknown. We performed integrative analyses in a Chinese cohort of peri-/post-menopausal women with metagenomics/targeted metabolomics/whole-genome sequencing to identify novel microbiome-related biomarkers for bone health. Bacteroides vulgatus was found to be negatively associated with bone mineral density (BMD), which was validated in US white people. Serum valeric acid (VA), a microbiota derived metabolite, was positively associated with BMD and causally downregulated by B. vulgatus. Ovariectomized mice fed B. vulgatus demonstrated increased bone resorption and poorer bone micro-structure, while those fed VA demonstrated reduced bone resorption and better bone micro-structure. VA suppressed RELA protein production (pro-inflammatory), and enhanced IL10 mRNA expression (anti-inflammatory), leading to suppressed maturation of osteoclast-like cells and enhanced maturation of osteoblasts in vitro. The findings suggest that B. vulgatus and VA may represent promising targets for osteoporosis prevention/treatment.
Topics: Humans; Female; Mice; Animals; Gastrointestinal Microbiome; Bone Resorption; Osteoporosis
PubMed: 37891329
DOI: 10.1038/s41467-023-42005-y -
Gastroenterology Jan 2023Weight loss and exercise intervention have been reported to increase the interaction between Bacteroides spp and Akkermansiamuciniphila (Am), although the underlying...
BACKGROUND & AIMS
Weight loss and exercise intervention have been reported to increase the interaction between Bacteroides spp and Akkermansiamuciniphila (Am), although the underlying mechanisms and consequences of the interaction remain unknown.
METHODS
Using a healthy Korean twin cohort (n = 582), we analyzed taxonomic associations with host body mass index. B vulgatus strains were isolated from mice and human subjects to investigate the strain-specific effect of B vulgatus SNUG 40005 (Bvul) on obesity. The mechanisms underlying Am enrichment by Bvul administration were investigated by multiple experiments: (1) in vitro cross-feeding experiments, (2) construction of Bvul mutants with the N-acetylglucosaminidase gene knocked out, and (3) in vivo validation cohorts with different metabolites. Finally, metabolite profiling in mouse and human fecal samples was performed.
RESULTS
An interaction between Bvul and Am was observed in lean subjects but was disrupted in obese subjects. The administration of Bvul to mice fed a high-fat diet decreased body weight, insulin resistance, and gut permeability. In particular, Bvul restored the abundance of Am, which decreased significantly after a long-term high-fat diet. A cross-feeding analysis of Am with cecal contents or Bvul revealed that Am enrichment was attributed to metabolites produced during mucus degradation by Bvul. The metabolome profile of mouse fecal samples identified N-acetylglucosamine as contributing to Am enrichment, which was confirmed by in vitro and in vivo experiments. Metabolite network analysis of the twin cohort found that lysine serves as a bridge between N-acetylglucosamine, Bvul, and Am.
CONCLUSIONS
Strain-specific microbe-microbe interactions modulate the mucosal environment via metabolites produced during mucin degradation in the gut.
Topics: Humans; Mice; Animals; Akkermansia; Acetylglucosamine; Bacteroides; Obesity; Diet, High-Fat
PubMed: 36240952
DOI: 10.1053/j.gastro.2022.09.040 -
Frontiers in Immunology 2022is one of the predominant species in the human gut and exerts a series of beneficial effects. The aim of this study was to investigate the protective role of Bv46 in...
INTRODUCTION
is one of the predominant species in the human gut and exerts a series of beneficial effects. The aim of this study was to investigate the protective role of Bv46 in a dextran sodium sulfate (DSS) induced colitis mouse model.
METHODS
Female C57BL/6J mice were given 3% DSS in drinking water to induce colitis and simultaneously treated with Bv46 by gavage for 7 days. Daily weight and disease activity index (DAI) of mice were recorded, and the colon length and histological changes were evaluated. The effects of Bv46 on gut microbiota composition, fecal short chain fatty acids (SCFAs) concentration, transcriptome of colon, colonic cytokine level and cytokine secretion of RAW 2647 macrophage cell line activated by the lipopolysaccharide (LPS) were assessed.
RESULTS AND DISCUSSION
Bv46 significantly attenuated symptoms of DSS-induced colitis in mice, including reduced DAI, prevented colon shortening, and alleviated colon histopathological damage. Bv46 modified the gut microbiota community of colitis mice and observably increased the abundance of , , and at the genus level. In addition, Bv46 treatment decreased the expression of colonic TNF-α, IL-1β and IL-6 in DSS-induced mouse colitis , reduced the secretion of TNF-α, IL-1β and IL-6 in macrophages stimulated by LPS , and downregulated the expression of and genes in mice colon, which mainly participate in the regulation of B cell responses. Furthermore, oral administration of Bv46 notably increased the contents of fecal SCFAs, especially butyric acid and propionic acid, which may contribute to the anti-inflammatory effect of Bv46. Supplementation with Bv46 serves as a promising strategy for the prevention of colitis.
Topics: Animals; Female; Humans; Mice; Bacteroides; Colitis; Cytokines; Dextran Sulfate; Fatty Acids, Volatile; Gastrointestinal Microbiome; Immunity; Interleukin-6; Lipopolysaccharides; Mice, Inbred C57BL; Tumor Necrosis Factor-alpha
PubMed: 36531989
DOI: 10.3389/fimmu.2022.1036196 -
Microbiology Spectrum Feb 2023Hyperlipidemia is a risk factor and key indicator for cardiovascular diseases, and the gut microbiota is highly associated with hyperlipidemia. Bacteroides vulgatus is a...
Hyperlipidemia is a risk factor and key indicator for cardiovascular diseases, and the gut microbiota is highly associated with hyperlipidemia. Bacteroides vulgatus is a prevalent mutualist across human populations and confers multiple health benefits such as immunoregulation, antiobesity, and coronary artery disease intervention. However, its role in antihyperlipidemia has not been systematically characterized. This study sought to identify the effect of B. vulgatus Bv46 on hyperlipidemia. Hyperlipidemic rats were modeled by feeding them a high-fat diet for 6 weeks. The effect of B. vulgatus Bv46 supplementation was evaluated by measuring anthropometric parameters, lipid and inflammation markers, and the liver pathology. Multi-omics was used to explore the underlying mechanisms. The ability of B. vulgatus Bv46 to produce bile salt hydrolase was confirmed by gene annotation and experiments. Oral administration of B. vulgatus Bv46 in hyperlipidemic rats significantly reduced the body weight gain, food efficiency, and liver index, improved the serum lipid profile, lowered the levels of serum inflammatory cytokines, promoted the loss of fecal bile acids (BAs), and extended the fecal pool of short-chain fatty acids (SCFAs), especially propionate and butyrate. B. vulgatus Bv46 induced compositional shifts of the gut microbial community of hyperlipidemic rats, characterized by a lower ratio of to with an increase of genera and . After intervention, serum metabolite profiling exhibited an adaptation in amino acids and glycerophospholipid metabolism. Transcriptomics further detected altered biological processes, including primary bile acid biosynthesis and fatty acid metabolic process. Taken together, the findings suggest that B. vulgatus Bv46 could be a promising candidate for interventions against hyperlipidemia. As a core microbe of the human gut ecosystem, Bacteroides vulgatus has been linked to multiple aspects of metabolic disorders in a collection of associative studies, which, while indicative, warrants more direct experimental evidence to verify. In this study, we experimentally demonstrated that oral administration of B. vulgatus Bv46 ameliorated the serum lipid profile and systemic inflammation of high-fat diet-induced hyperlipidemic rats in a microbiome-regulated manner, which appears to be associated with changes of bile acid metabolism, short-chain fatty acid biosynthesis, and serum metabolomic profile. This finding supports the causal contribution of B. vulgatus in host metabolism and helps to form the basis of novel therapies for the treatment of hyperlipidemia.
Topics: Rats; Humans; Animals; Gastrointestinal Microbiome; Ecosystem; Bacteroides; Hyperlipidemias; Fatty Acids, Volatile; Inflammation; Lipid Metabolism; Bile Acids and Salts
PubMed: 36625637
DOI: 10.1128/spectrum.02517-22 -
Frontiers in Microbiology 2023Patients with inflammatory bowel disease (IBD) have a higher prevalence of depression. Gut microbiota dysbiosis plays an important role in IBD and depression. However,...
BACKGROUND
Patients with inflammatory bowel disease (IBD) have a higher prevalence of depression. Gut microbiota dysbiosis plays an important role in IBD and depression. However, few studies have explored the characteristic microbiota of patients with IBD and depression (IBDD), or their role in IBDD.
METHODS
We performed deep metagenomic sequencing and 16S rDNA quantitative PCR to characterise the gut microbial communities of patients with IBDD and patients with IBD without depression (IBDND). We then assessed the effect of the microbiota on colitis and depression in mouse models of dextran sulfate sodium salt (DSS)-induced colitis and lipopolysaccharide (LPS)-induced depression. Furthermore, liquid chromatography-tandem mass spectrometry was used to analyse the microbiota-derived metabolites involved in gut-brain communication. Evans Blue tracer dye was used to assess blood-brain barrier (BBB) permeability.
RESULTS
Our results showed that the faecal abundance of () was lower in patients with IBDD than in those with IBDND. In the DSS-induced colitis mouse model, the group showed a significantly lower disease activity index score, lesser weight loss, and longer colon length than the DSS group. Moreover, relieved depression-like behaviour in the DSS-induced colitis mouse model and in the LPS-induced depression mouse model. Furthermore, the key metabolite of was p-hydroxyphenylacetic acid (4-HPAA), which was found to relieve intestinal inflammation and alleviate depression-like behaviours in mouse models. By increasing the expression of the tight junction protein claudin-5 in the vascular endothelium of the BBB, and 4-HPAA play critical roles in gut-brain communication.
CONCLUSION
and -derived 4-HPAA ameliorated intestinal inflammation and relieved depressive symptoms through the gut-brain axis. Thus, administration of or 4-HPAA supplementation is a promising therapeutic strategy for treating IBD, particularly IBDD.
PubMed: 38033588
DOI: 10.3389/fmicb.2023.1287271 -
Biology Nov 2022The 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.... (Review)
Review
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 and the ratio of was found to be increased while that of ML615J-28 124-7 and S24-7 was reduced. In breast cancer, the abundance of was enhanced, while in cervical cancer, and were enhanced but and members of were decreased. In ovarian cancer, abundance was increased. Interestingly, the administration of , and ameliorated PCOS symptoms while that of a mix of W51, W23, W63, W52, W24, W37, W19, W56, and W58 alleviated vascular malfunction and arterial stiffness in obese postmenopausal women, and finally, while further research is needed, 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.
PubMed: 36421397
DOI: 10.3390/biology11111683 -
Bone Jan 2021There is a need to discover additional kinds of intestinal microbiota to supplement the probiotic-treatment of postmenopausal osteoporosis. Increasing evidence has...
There is a need to discover additional kinds of intestinal microbiota to supplement the probiotic-treatment of postmenopausal osteoporosis. Increasing evidence has indicated that Bacteroides vulgatus has potential as a probiotic for ameliorating postmenopausal bone loss. In this study, ovariectomized female C57/BL6 mice were treated with B. vulgatus ATCC 8482 gavage to investigate the differences in colonic microbiota composition, inflammation signal pathways, inflammatory cytokines, bone turnover markers, and lumbar vertebrae microstructure compared with the control group. Our results show that B. vulgatus ATCC 8482 diminished microbiota dysbiosis and subsequently down-regulated the colonic lipopolysaccharide/TLR-4/p-NF-κB pathway leading to decreased serum TNF-α. This reduced TNF-α/RANKL expression and induced ALP and Runx-2 expression in the 5th lumbar vertebra, leading to amelioration of bone loss and microstructure destruction in the lumbar vertebra of ovariectomized mice. Taken together, these results indicate that B. vulgatus could be a probiotic for treatment of postmenopausal lumbar osteoporosis.
Topics: Animals; Bacteroides; Dysbiosis; Female; Gastrointestinal Microbiome; Humans; Mice; NF-kappa B; Ovariectomy
PubMed: 33148507
DOI: 10.1016/j.bone.2020.115710 -
International Journal of Molecular... Feb 2021Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disease. The hypothesis that alterations in the microbiome are involved in the genesis of PCOS... (Review)
Review
Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disease. The hypothesis that alterations in the microbiome are involved in the genesis of PCOS has been postulated. Aim of this review is to summarize the available literature data about the relationship between microbiome and PCOS. A search on PubMed and Medline databases was performed from inception to November 20Most of evidence has focused on the connection of intestinal bacteria with sex hormones and insulin-resistance: while in the first case, a relationship with hyperandrogenism has been described, although it is still unclear, in the second one, chronic low-grade inflammation by activating the immune system, with increased production of proinflammatory cytokines which interfere with insulin receptor function, causing IR (Insulin Resistance)/hyperinsulinemia has been described, as well as the role of gastrointestinal hormones like Ghrelin and peptide YY (PYY), bile acids, interleukin-22 and Bacteroides vulgatus have been highlighted. The lower genital tract microbiome would be affected by changes in PCOS patients too. The therapeutic opportunities include probiotic, prebiotics and synbiotics, as well as fecal microbiota transplantation and the use of IL-22, to date only in animal models, as a possible future drug. Current evidence has shown the involvement of the gut microbiome in PCOS, seen how humanized mice receiving a fecal transplant from women with PCOS develop ovarian dysfunction, immune changes and insulin resistance and how it is capable of disrupting the secondary bile acid biosynthesis. A future therapeutic approach for PCOS may involve the human administration of IL-22 and bile acid glycodeoxycholic acid.
Topics: Animals; Diet; Female; Gastrointestinal Microbiome; Genitalia, Female; Hormones; Humans; Insulin Resistance; Polycystic Ovary Syndrome
PubMed: 33669557
DOI: 10.3390/ijms22042048