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Nutrients Dec 2022Fecal microbiota transplantation (FMT) is a promising therapeutic modality for the treatment and prevention of metabolic disease. We previously conducted a double-blind,... (Randomized Controlled Trial)
Randomized Controlled Trial
Fecal microbiota transplantation (FMT) is a promising therapeutic modality for the treatment and prevention of metabolic disease. We previously conducted a double-blind, randomized, placebo-controlled pilot trial of FMT in obese metabolically healthy patients in which we found that FMT enhanced gut bacterial bile acid metabolism and delayed the development of impaired glucose tolerance relative to the placebo control group. Therefore, we conducted a secondary analysis of fecal samples collected from these patients to assess the potential gut microbial species contributing to the effect of FMT to improve metabolic health and increase gut bacterial bile acid metabolism. Fecal samples collected at baseline and after 4 weeks of FMT or placebo treatment underwent shotgun metagenomic analysis. Ultra-high-performance liquid chromatography-mass spectrometry was used to profile fecal bile acids. FMT-enriched bacteria that have been implicated in gut bile acid metabolism included and . To identify candidate bacteria involved in gut microbial bile acid metabolism, we assessed correlations between bacterial species abundance and bile acid profile, with a focus on bile acid products of gut bacterial metabolism. and were positively correlated with unconjugated bile acids. , , and were positively correlated with secondary bile acids. Together, these data identify several candidate bacteria that may contribute to the metabolic benefits of FMT and gut bacterial bile acid metabolism that requires further functional validation.
Topics: Humans; Fecal Microbiota Transplantation; Gastrointestinal Microbiome; Feces; Bacteria; Bile Acids and Salts
PubMed: 36558359
DOI: 10.3390/nu14245200 -
Nutrients Feb 2021The aim of this study was to investigate the effects of 24-week synbiotic supplementation on chronic inflammation and the gut microbiota in obese patients with type 2... (Randomized Controlled Trial)
Randomized Controlled Trial
The aim of this study was to investigate the effects of 24-week synbiotic supplementation on chronic inflammation and the gut microbiota in obese patients with type 2 diabetes. We randomized 88 obese patients with type 2 diabetes to one of two groups for 24 weeks: control or synbiotic ( strain Shirota (previously strain Shirota) and strain Yakult, and galactooligosaccharides). The primary endpoint was the change in interleukin-6 from baseline to 24 weeks. Secondary endpoints were evaluation of the gut microbiota in feces and blood, fecal organic acids, high-sensitivity C-reactive protein, lipopolysaccharide-binding protein, and glycemic control. Synbiotic administration for 24 weeks did not significantly affect changes in interleukin-6 from baseline to 24 weeks (0.35 ± 1.99 vs. -0.24 ± 1.75 pg/mL, respectively). Relative to baseline, however, at 24 weeks after synbiotic administration there were positive changes in the counts of and total lactobacilli, the relative abundances of species such as and , and the concentrations of acetic and butyric acids in feces. No significant changes in inflammatory markers were found in the synbiotic group compared to the control group. However, synbiotic administration at least partially improved the gut environment in obese patients with type 2 diabetes.
Topics: Aged; Bifidobacterium breve; C-Reactive Protein; Chronic Disease; Diabetes Mellitus, Type 2; Feces; Female; Gastrointestinal Microbiome; Humans; Inflammation; Inflammation Mediators; Lacticaseibacillus casei; Male; Middle Aged; Obesity; Synbiotics; Treatment Outcome
PubMed: 33567701
DOI: 10.3390/nu13020558 -
Frontiers in Immunology 2022In clinical practice, fecal microbiota transplantation (FMT) has been used to treat inflammatory bowel disease (IBD), and has shown certain effects. However, the...
In clinical practice, fecal microbiota transplantation (FMT) has been used to treat inflammatory bowel disease (IBD), and has shown certain effects. However, the selection of FMT donors and the mechanism underlying the effect of FMT intervention in IBD require further exploration. In this study, dextran sodium sulfate (DSS)-induced colitis mice were used to determine the differences in the protection of colitis symptoms, inflammation, and intestinal barrier, by FMT from two donors. Intriguingly, pre-administration of healthy bacterial fluid significantly relieved the symptoms of colitis compared to the ulcerative colitis (UC) bacteria. In addition, healthy donor (HD) bacteria significantly reduced the levels of inflammatory markers Myeloperoxidase (MPO) and Eosinophil peroxidase (EPO), and various pro-inflammatory factors, in colitis mice, and increased the secretion of the anti-inflammatory factor IL-10. Metagenomic sequencing indicated higher species diversity and higher abundance of anti-inflammatory bacteria in the HD intervention group, including , , , short-chain fatty acids (SCFAs)-producing bacterium , and secondary bile acids (SBAs)-producing bacterium . In the UC intervention group, the SCFA-producing bacterium , IBD-related bacterium , , and the conditional pathogen , were more abundant. Metabolomics analysis showed that the two types of FMT significantly modulated the metabolism of DSS-induced mice. Moreover, compared with the UC intervention group, indoleacetic acid and unsaturated fatty acids (DHA, DPA, and EPA) with anti-inflammatory effects were significantly enriched in the HD intervention group. In summary, these results indicate that FMT can alleviate the symptoms of colitis, and the effect of HD intervention is better than that of UC intervention. This study offers new insights into the mechanisms of FMT clinical intervention in IBD.
Topics: Animals; Anti-Inflammatory Agents; Bacteria; Colitis; Colitis, Ulcerative; Dextran Sulfate; Fecal Microbiota Transplantation; Gastrointestinal Microbiome; Humans; Mice
PubMed: 35237276
DOI: 10.3389/fimmu.2022.836542 -
Neurobiology of Stress May 2021Stress has been shown to disturb the balance of human intestinal microbiota and subsequently causes mental health problems like anxiety and depression. Our previous...
Stress has been shown to disturb the balance of human intestinal microbiota and subsequently causes mental health problems like anxiety and depression. Our previous study showed that ingesting the probiotic strain, (.) P-8, for 12 weeks could alleviate stress and anxiety of stressed adults. The current study was a follow-up work aiming to investigate the functional role of the gut metagenomes in the observed beneficial effects. The fecal metagenomes of the probiotic (n = 43) and placebo (n = 36) receivers were analyzed in depth. The gut microbiomes of the placebo group at weeks 0 and 12 showed a significantly greater Aitchison distance ( < 0.001) compared with the probiotic group. Meanwhile, the Shannon diversity index of the placebo group ( < 0.05) but not the probiotic group decreased significantly at week 12. Additionally, significantly more species-level genome bins (SGBs) of , , and ( < 0.01) were identified in the fecal metagenomes of the probiotic group, while the abundances of SGBs representing the species and decreased significantly ( < 0.05). Furthermore, the 12-week probiotic supplementation enhanced the diversity of neurotransmitter-synthesizing/consuming SGBs and the levels of some predicted microbial neuroactive metabolites (e.g., short-chain fatty acids, gamma-aminobutyric acid, arachidonic acid, and sphingomyelin). Our results showed a potential link between probiotic-induced gut microbiota modulation and stress/anxiety alleviation in stressed adults, supporting that the gut-brain axis was involved in relieving stress-related symptoms. The beneficial effect relied not only on microbial diversity changes but more importantly gut metagenome modulations at the SGB and functional gene levels.
PubMed: 33511258
DOI: 10.1016/j.ynstr.2021.100294 -
Gut May 2011A general dysbiosis of the intestinal microbiota has been established in patients with Crohn's disease (CD), but a systematic characterisation of this dysbiosis is...
BACKGROUND AND AIMS
A general dysbiosis of the intestinal microbiota has been established in patients with Crohn's disease (CD), but a systematic characterisation of this dysbiosis is lacking. Therefore the composition of the predominant faecal microbiota of patients with CD was studied in comparison with the predominant composition in unaffected controls. Whether dysbiosis is present in relatives of patients CD was also examined.
METHODS
Focusing on families with at least three members affected with CD, faecal samples of 68 patients with CD, 84 of their unaffected relatives and 55 matched controls were subjected to community fingerprinting of the predominant microbiota using denaturing gradient gel electrophoresis (DGGE). To analyse the DGGE profiles, BioNumerics software and non-parametric statistical analyses (SPSS V.17.0) were used. Observed differences in the predominant microbiota were subsequently confirmed and quantified with real-time PCR.
RESULTS
Five bacterial species characterised dysbiosis in CD, namely a decrease in Dialister invisus (p=0.04), an uncharacterised species of Clostridium cluster XIVa (p = 0.03), Faecalibacterium prausnitzii (p < 1.3 × 10⁻⁵) and Bifidobacterium adolescentis (p = 5.4 × 10⁻⁶), and an increase in Ruminococcus gnavus (p = 2.1 × 10⁻⁷). Unaffected relatives of patients with CD had less Collinsella aerofaciens (p = 0.004) and a member of the Escherichia coli-Shigella group (p = 0.01) and more Ruminococcus torques (p = 0.02) in their predominant microbiota as compared with healthy subjects.
CONCLUSION
Unaffected relatives of patients with CD have a different composition of their microbiota compared with healthy controls. This dysbiosis is not characterised by lack of butyrate producing-bacteria as observed in CD but suggests a role for microorganisms with mucin degradation capacity.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteria; Case-Control Studies; Crohn Disease; DNA, Bacterial; Denaturing Gradient Gel Electrophoresis; Feces; Female; Humans; Male; Metagenome; Middle Aged; Reverse Transcriptase Polymerase Chain Reaction; Symbiosis; Young Adult
PubMed: 21209126
DOI: 10.1136/gut.2010.223263 -
Nature Metabolism Mar 2024Emerging evidence suggests that modulation of gut microbiota by dietary fibre may offer solutions for metabolic disorders. In a randomized placebo-controlled crossover... (Randomized Controlled Trial)
Randomized Controlled Trial
Emerging evidence suggests that modulation of gut microbiota by dietary fibre may offer solutions for metabolic disorders. In a randomized placebo-controlled crossover design trial (ChiCTR-TTRCC-13003333) in 37 participants with overweight or obesity, we test whether resistant starch (RS) as a dietary supplement influences obesity-related outcomes. Here, we show that RS supplementation for 8 weeks can help to achieve weight loss (mean -2.8 kg) and improve insulin resistance in individuals with excess body weight. The benefits of RS are associated with changes in gut microbiota composition. Supplementation with Bifidobacterium adolescentis, a species that is markedly associated with the alleviation of obesity in the study participants, protects male mice from diet-induced obesity. Mechanistically, the RS-induced changes in the gut microbiota alter the bile acid profile, reduce inflammation by restoring the intestinal barrier and inhibit lipid absorption. We demonstrate that RS can facilitate weight loss at least partially through B. adolescentis and that the gut microbiota is essential for the action of RS.
Topics: Animals; Humans; Male; Mice; Gastrointestinal Microbiome; Obesity; Overweight; Resistant Starch; Weight Gain; Weight Loss; Cross-Over Studies
PubMed: 38409604
DOI: 10.1038/s42255-024-00988-y -
Journal of Experimental & Clinical... Jul 2023The interplay between gut microbiota and tumor microenvironment (TME) in the pathogenesis of colorectal cancer (CRC) is largely unknown. Here, we elucidated the...
BACKGROUND
The interplay between gut microbiota and tumor microenvironment (TME) in the pathogenesis of colorectal cancer (CRC) is largely unknown. Here, we elucidated the functional role of B. adolescentis and its possible mechanism on the manipulation of Decorin macrophages in colorectal cancer.
METHODS
The relative abundance of B. adolescentis in tumor or para-tumor tissue of CRC patients was analyzed. The role of B. adolescentis was explored in the CRC animal models. The single cell-RNA sequencing (scRNA-seq) was used to investigate the myeloid cells subsets in TME. The expression level of TLR2/YAP axis and its downstream Decorin in macrophages were tested by Western blot and qRT-PCR. Knockdown of Decorin in Raw264.7 was performed to investigate the effect of Decorin macrophages on subcutaneous tumor formation. Multi-immunofluorescence assay examined the number of Decorin macrophages on the CRC tissue.
RESULTS
We found that the abundance of B. adolescentis was significantly reduced in tumor tissue of CRC patients. Supplementation with B. adolescentis suppressed AOM/DSS-induced tumorigenesis in mice. ScRNA-seq and animal experiment revealed that B. adolescentis increased Decorin macrophages. Mechanically, Decorin was activated by TLR2/YAP axis in macrophages. The abundance of B. adolescentis was correlated with the number of Decorin macrophages and the expression level of TLR2 in tumor tissue of CRC patients.
CONCLUSIONS
These results highlight that B. adolescentis induced Decorin macrophages and provide a novel therapeutic target for probiotic-based modulation of immune microenvironment in CRC.
Topics: Animals; Mice; Bifidobacterium adolescentis; Decorin; Toll-Like Receptor 2; Carcinogenesis; Macrophages; Colorectal Neoplasms; Tumor Microenvironment
PubMed: 37464382
DOI: 10.1186/s13046-023-02746-6 -
Frontiers in Endocrinology 2021The gut microbiota is a newly identified contributor to the development of non-alcoholic fatty liver disease (NAFLD). Previous studies of (), a species of that is...
The gut microbiota is a newly identified contributor to the development of non-alcoholic fatty liver disease (NAFLD). Previous studies of (), a species of that is common in the human intestinal tract, have demonstrated that it can alleviate liver steatosis and steatohepatitis. Fibroblast growth factor 21 (FGF21) has long been considered as a biomarker of NAFLD, and recent studies have shown the protective effect of FGF21 analogs on NAFLD. We wondered whether treatment would alleviate NAFLD via the interaction with FGF21. To this end, male C57BL/6J mice on a choline-deficient high-fat diet (CDHFD) were treated with drinking water supplemented with for 8 weeks, followed by the acute administration of recombinant mouse FGF21 protein (rmFGF21) to conduct the FGF21 response test. Consistent with previous studies, supplementation reversed the CDHFD-induced liver steatosis and steatohepatitis. This was evaluated on the NAFLD activity score (NAS), reduced liver enzymes, and lipid accumulation. Further studies demonstrated that supplementation preserved the gut barrier, reduced the gut microbiota-derived lipopolysaccharide (LPS), and inhibited the hepatic TLR4/NF-κB pathway. This was accompanied by the elevated expressions of the receptors of FGF21, fibroblast growth factor receptor 1 (FGFR1) and β-klotho (KLB), in the liver and the decreased expression of FGF21. The results of FGF21 response test showed that supplementation alleviated the CDHFD-induced FGF21 resistance. In vivo experiments suggested that LPS could suppress the expression of FGF21 and KLB in a dose-dependent manner. Collectively, this study showed that supplementation could alleviate NAFLD by increasing FGF21 sensitivity.
Topics: Animals; Bifidobacterium adolescentis; Diet, High-Fat; Fatty Liver; Fibroblast Growth Factors; Gastrointestinal Microbiome; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease
PubMed: 35035378
DOI: 10.3389/fendo.2021.773340 -
European Journal of Nutrition Oct 2020Compared to a healthy population, the gut microbiota in type 2 diabetes presents with several unfavourable features that may impair glucose regulation. The aim of this... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Compared to a healthy population, the gut microbiota in type 2 diabetes presents with several unfavourable features that may impair glucose regulation. The aim of this study was to evaluate the prebiotic effect of inulin-type fructans on the faecal microbiota and short-chain fatty acids (SCFA) in patients with type 2 diabetes.
METHODS
The study was a placebo controlled crossover study, where 25 patients (15 men) aged 41-71 years consumed 16 g of inulin-type fructans (a mixture of oligofructose and inulin) and 16-g placebo (maltodextrin) for 6 weeks in randomised order. A 4-week washout separated the 6 weeks treatments. The faecal microbiota was analysed by high-throughput 16S rRNA amplicon sequencing and SCFA in faeces were analysed using vacuum distillation followed by gas chromatography.
RESULTS
Treatment with inulin-type fructans induced moderate changes in the faecal microbiota composition (1.5%, p = 0.045). A bifidogenic effect was most prominent, with highest positive effect on operational taxonomic units (OTUs) of Bifidobacterium adolescentis, followed by OTUs of Bacteroides. Significantly higher faecal concentrations of total SCFA, acetic acid and propionic acid were detected after prebiotic consumption compared to placebo. The prebiotic fibre had no effects on the concentration of butyric acid or on the overall microbial diversity.
CONCLUSION
Six weeks supplementation with inulin-type fructans had a significant bifidogenic effect and induced increased concentrations of faecal SCFA, without changing faecal microbial diversity. Our findings suggest a moderate potential of inulin-type fructans to improve gut microbiota composition and to increase microbial fermentation in type 2 diabetes.
TRIAL REGISTRATION
The trial is registered at clinicaltrials.gov (NCT02569684).
Topics: Adult; Aged; Cross-Over Studies; Diabetes Mellitus, Type 2; Fatty Acids, Volatile; Feces; Female; Fermentation; Gastrointestinal Microbiome; Humans; Inulin; Male; Middle Aged; Prebiotics; RNA, Ribosomal, 16S
PubMed: 32440730
DOI: 10.1007/s00394-020-02282-5 -
Trends in Microbiology Oct 2022Bifidobacteria are among the earliest and most abundant bacterial colonizers of the neonatal gut in many mammals, where they elicit purported host health benefits. While... (Review)
Review
Bifidobacteria are among the earliest and most abundant bacterial colonizers of the neonatal gut in many mammals, where they elicit purported host health benefits. While early life-associated dynamics and diversity, as well as the metabolic and beneficial activities, of Bifidobacterium species have been well studied, functional contributions of bifidobacteria to health and well-being of adults remain less explored. In this opinion piece, we discuss the current knowledge regarding the relevance of endogenous Bifidobacterium species associated with adulthood. We identify knowledge gaps and discuss opportunities for microbiota enrichment with rationally selected strains of Bifidobacterium more adapted to the adult host. We propose that current knowledge and future studies in this area will help us to better understand the ecological, metabolic, and functional roles played by Bifidobacterium in the gut ecosystem across various host ages.
Topics: Adult; Animals; Bacteria; Bifidobacterium; Gastrointestinal Microbiome; Humans; Infant, Newborn; Mammals; Microbiota
PubMed: 35577716
DOI: 10.1016/j.tim.2022.04.004