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Arthritis & Rheumatology (Hoboken, N.J.) Sep 2021Systemic inflammatory factors have been implicated in symptomatic hand osteoarthritis (OA). Gut microbiome dysbiosis promotes systemic inflammation. The aim of this...
OBJECTIVE
Systemic inflammatory factors have been implicated in symptomatic hand osteoarthritis (OA). Gut microbiome dysbiosis promotes systemic inflammation. The aim of this study was to examine the association between the gut microbiome and the presence of symptomatic hand OA in a population-based study.
METHODS
Study participants were subjects of the Xiangya Osteoarthritis Study, a community-based observational study conducted in the Hunan Province of China. Symptomatic hand OA was defined as the presence of both symptoms and radiographic OA in the same hand. The gut microbiome was analyzed using 16S ribosomal RNA gene sequencing in stool samples. We examined the relation of α-diversity, β-diversity, relative abundance of taxa, and potential bacterial functional pathways to symptomatic hand OA.
RESULTS
A total of 1,388 participants (mean age 61.3 years, 57.4% women) were included in the study, of whom 72 had symptomatic hand OA (prevalence of symptomatic hand OA 5.2%). Beta-diversity of the gut microbiome, but not α-diversity, was significantly associated with the presence of symptomatic hand OA (P = 0.003). Higher relative abundance of the genera Bilophila and Desulfovibrio as well as lower relative abundance of the genus Roseburia was associated with symptomatic hand OA. Most functional pathways (i.e., those annotated in the KEGG Ortholog hierarchy) that were observed to be altered in participants with symptomatic hand OA belonged to the amino acid, carbohydrate, and lipid metabolic pathways.
CONCLUSION
This large, population-based study provides the first evidence that alterations in the composition of the gut microbiome were observed among study participants who had symptomatic hand OA, and a low relative abundance of Roseburia but high relative abundance of Bilophila and Desulfovibrio at the genus level were associated with prevalent symptomatic hand OA. These findings may help investigators understand the role of the microbiome in the development of symptomatic hand OA and could contribute to potential translational opportunities.
Topics: Adult; Aged; Feces; Female; Gastrointestinal Microbiome; Hand Joints; Humans; Male; Middle Aged; Osteoarthritis; RNA, Ribosomal, 16S
PubMed: 33760399
DOI: 10.1002/art.41729 -
American Journal of Physiology.... Dec 2021Emerging evidence links dietary fiber with altered gut microbiota composition and bile acid signaling in maintaining metabolic health. Yeast β-glucan (Y-BG) is a... (Comparative Study)
Comparative Study
Emerging evidence links dietary fiber with altered gut microbiota composition and bile acid signaling in maintaining metabolic health. Yeast β-glucan (Y-BG) is a dietary supplement known for its immunomodulatory effect, yet its impact on the gut microbiota and bile acid composition remains unclear. This study investigated whether dietary forms of Y-BG modulate these gut-derived signals. We performed 4-wk dietary supplementation in healthy mice to evaluate the effects of different fiber composition (soluble vs. particulate Y-BG) and dose (0.1% vs. 2%). We found that 2% particulate Y-BG induced robust gut microbiota community shifts with elevated liver mRNA abundance and bile acid synthesis. These diet-induced responses were notably different when compared with the prebiotic inulin, and included a marked reduction in fecal abundance which we demonstrated as translatable to obesity in population-scale American Gut and TwinsUK clinical cohorts. This prompted us to test whether 2% Y-BG maintained metabolic health in mice fed 60% HFD over 13 wk. Y-BG consistently altered the gut microbiota composition and reduced abundance, with trends observed in improvement of metabolic phenotype. Notably, Y-BG improved insulin sensitization and this was associated with enhanced ileal mRNA accumulation and reduced abundance. Collectively, our results demonstrate that Y-BG modulates gut microbiota community composition and bile acid signaling, but the dietary regime needs to be optimized to facilitate clinical improvement in metabolic phenotype in an aggressive high-fat diet animal model. The study shows that dietary Y-BG supplementation modulated gut microbiota, bile acid metabolism and associated signaling pathways. Y-BG significantly reduced abundance which is associated with obesity in human cohorts. Correlation analysis confirmed functional interactions between bile acid composition, gut microbiota, and metabolic phenotype, although clinical benefit did not reach significance in an aggressive obesity model. Gut microbiota and bile acids correlated with metabolic parameters, indicating future potential of dietary Y-BG modulation of metabolic pathways.
Topics: Animals; Bile Acids and Salts; Bilophila; Cholesterol 7-alpha-Hydroxylase; Diet, High-Fat; Dietary Fiber; Disease Models, Animal; Gastrointestinal Microbiome; Glucagon-Like Peptide-1 Receptor; Insulin Resistance; Intestine, Small; Inulin; Liver; Male; Mice, Inbred C57BL; Obesity; Receptors, Cytoplasmic and Nuclear; Signal Transduction; Yeasts; beta-Glucans; Mice
PubMed: 34643089
DOI: 10.1152/ajpgi.00226.2021 -
International Journal of Medical... Jul 2021Sulfur metabolism and sulfur-containing metabolites play an important role in the human digestive system, and sulfur compounds and pathways are associated with... (Review)
Review
Sulfur metabolism and sulfur-containing metabolites play an important role in the human digestive system, and sulfur compounds and pathways are associated with inflammatory bowel diseases (IBD). In fact, cysteine metabolism results in the production of taurine and sulfate, and gut microbes catabolize them into hydrogen sulfide, a signaling molecule with various biological functions. Besides metabolites originating from sulfur metabolism, several other sulfur-containing metabolites of different classes were detected in human feces, consisting of non-volatile and volatile compounds. Sulfated steroids and bile acids such as taurine-conjugated bile acids are the major classes along with sulfur amino acids and sulfur-containing peptides. Indeed, sulfur-containing metabolites were described in stool samples from healthy subjects, patients suffering from colorectal cancer or IBD. In metabolomics-driven studies, around 50 known sulfur-containing metabolites were linked to IBD. Taurine, taurocholic acid, taurochenodeoxycholic acid, methionine, methanethiol and hydrogen sulfide were regularly reported in IBD studies, and most of them were elevated in stool samples from IBD patients. We summarized from this review that there is strong interplay between perturbed gut microbiota in IBD, and the consistently higher abundance of sulfur-containing metabolites, which potentially represent substrates for sulfidogenic bacteria such as Bilophila or Escherichia and promote their growth. These bacteria might shift their metabolism towards the degradation of taurine and cysteine and therefore to a higher hydrogen sulfide production.
Topics: Feces; Gastrointestinal Microbiome; Humans; Inflammatory Bowel Diseases; Metabolome; Sulfur
PubMed: 34147944
DOI: 10.1016/j.ijmm.2021.151513 -
Frontiers in Immunology 2023Immune checkpoint inhibitors have had a major impact on cancer treatment. Gut microbiota plays a major role in the cancer microenvironment, affecting treatment response....
INTRODUCTION
Immune checkpoint inhibitors have had a major impact on cancer treatment. Gut microbiota plays a major role in the cancer microenvironment, affecting treatment response. The gut microbiota is highly individual, and varies with factors, such as age and race. Gut microbiota composition in Japanese cancer patients and the efficacy of immunotherapy remain unknown.
METHODS
We investigated the gut microbiota of 26 patients with solid tumors prior to immune checkpoint inhibitor monotherapy to identify bacteria involved in the efficacy of these drugs and immune-related adverse events (irAEs).
RESULTS
The genera and were relatively common in the group showing efficacy towards the anti-PD-1 antibody treatment (effective group). The proportions of (P = 0.022) and (P = 0.049) were significantly higher in the effective group than in the ineffective group. In addition, the proportion of (P = 0.033) was significantly higher in the ineffective group. Next, they were divided into irAE and non-irAE groups. The proportions of (P = 0.001) and (P = 0.001) were significantly higher in the group with irAEs than in those without, while the proportions of (P = 0.013) and the unclassified (P = 0.027) were significantly higher in the group without irAEs than those with. Furthermore, within the Effective group, and (both P = 0.001) were more abundant in the subgroup with irAEs than in those without them. In contrast, (P = 0.021) and (P= 0.033) were statistically significantly more common in those without irAEs.
DISCUSSION
Our Study suggests that the analysis of the gut microbiota may provide future predictive markers for the efficacy of cancer immunotherapy or the selection of candidates for fecal transplantation for cancer immunotherapy.
Topics: Humans; Immune Checkpoint Inhibitors; Acidaminococcus; Neoplasms; Immunotherapy; Tumor Microenvironment
PubMed: 37207204
DOI: 10.3389/fimmu.2023.1164724 -
Nature Communications Sep 2023Taurine-respiring gut bacteria produce HS with ambivalent impact on host health. We report the isolation and ecophysiological characterization of a taurine-respiring...
Taurine-respiring gut bacteria produce HS with ambivalent impact on host health. We report the isolation and ecophysiological characterization of a taurine-respiring mouse gut bacterium. Taurinivorans muris strain LT0009 represents a new widespread species that differs from the human gut sulfidogen Bilophila wadsworthia in its sulfur metabolism pathways and host distribution. T. muris specializes in taurine respiration in vivo, seemingly unaffected by mouse diet and genotype, but is dependent on other bacteria for release of taurine from bile acids. Colonization of T. muris in gnotobiotic mice increased deconjugation of taurine-conjugated bile acids and transcriptional activity of a sulfur metabolism gene-encoding prophage in other commensals, and slightly decreased the abundance of Salmonella enterica, which showed reduced expression of galactonate catabolism genes. Re-analysis of metagenome data from a previous study further suggested that T. muris can contribute to protection against pathogens by the commensal mouse gut microbiota. Together, we show the realized physiological niche of a key murine gut sulfidogen and its interactions with selected gut microbiota members.
Topics: Humans; Animals; Mice; Affect; Bile Acids and Salts; Salmonella enterica; Taurine; Sulfur
PubMed: 37723166
DOI: 10.1038/s41467-023-41008-z -
Clinical Microbiology Reviews Jul 2013Susceptibility testing of anaerobic bacteria recovered from selected cases can influence the choice of antimicrobial therapy. The Clinical and Laboratory Standards... (Review)
Review
Susceptibility testing of anaerobic bacteria recovered from selected cases can influence the choice of antimicrobial therapy. The Clinical and Laboratory Standards Institute (CLSI) has standardized many laboratory procedures, including anaerobic susceptibility testing (AST), and has published documents for AST. The standardization of testing methods by the CLSI allows comparisons of resistance trends among various laboratories. Susceptibility testing should be performed on organisms recovered from sterile body sites, those that are isolated in pure culture, or those that are clinically important and have variable or unique susceptibility patterns. Organisms that should be considered for individual isolate testing include highly virulent pathogens for which susceptibility cannot be predicted, such as Bacteroides, Prevotella, Fusobacterium, and Clostridium spp.; Bilophila wadsworthia; and Sutterella wadsworthensis. This review describes the current methods for AST in research and reference laboratories. These methods include the use of agar dilution, broth microdilution, Etest, and the spiral gradient endpoint system. The antimicrobials potentially effective against anaerobic bacteria include beta-lactams, combinations of beta-lactams and beta-lactamase inhibitors, metronidazole, chloramphenicol, clindamycin, macrolides, tetracyclines, and fluoroquinolones. The spectrum of efficacy, antimicrobial resistance mechanisms, and resistance patterns against these agents are described.
Topics: Animals; Anti-Bacterial Agents; Bacteria, Anaerobic; Bacterial Infections; Bacteriological Techniques; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests
PubMed: 23824372
DOI: 10.1128/CMR.00086-12 -
Frontiers in Endocrinology 2022In adults, gut dysbiosis may contribute to the pathogenesis of gout. However, the characteristics of gut microbiota in children with hyperuricemia (HUA) in the absence...
BACKGROUND
In adults, gut dysbiosis may contribute to the pathogenesis of gout. However, the characteristics of gut microbiota in children with hyperuricemia (HUA) in the absence of clinical gout have not been explored.
OBJECTIVE
This present study analyzed the gut microbiota in children with HUA as compared to controls (Con) and explored bacterial associations that may account for differences.
METHODS
A total of 80 children were enrolled in this study; they were divided into HUA and Con according to the level of serum uric acid (UA). The composition of gut microbiota was investigated by 16S rRNA high-throughput sequencing.
RESULTS
Principal coordinate analysis revealed that gut microbiota of the HUA group was clustered together and separated partly from the Con group. There was no difference in alpha-diversity between the two groups. However, Spearman's correlation analysis revealed that serum UA level positively correlated with genera , and , and negatively associated with the producers of short-chain fatty acids (SCFAs), such as , and , and the sulfidogenic bacteria The members of the genera and in the Con group were significantly more prevalent than the HUA subjects. Compared to the Con cohort, metabolic pathway predictions found that the superpathways of purine nucleotide biosynthesis were decreased in HUA subjects, whereas the superpathway of purine deoxyribonucleoside de gradation was increased.
CONCLUSION
The composition of the gut microbiota in children with HUA differs from Con. Although causality cannot be established, modification in the microbiota that produces SCFA and sulfide may promote HUA.
Topics: Adult; Bacteria; Child; Gastrointestinal Microbiome; Gout; Humans; Hyperuricemia; RNA, Ribosomal, 16S; Uric Acid
PubMed: 35574004
DOI: 10.3389/fendo.2022.848715 -
Heliyon Dec 2023Polycystic ovary syndrome (PCOS) is a multifaceted endocrine and metabolic syndrome with complex origins and pathogenesis that has not yet been fully elucidated....
BACKGROUND
Polycystic ovary syndrome (PCOS) is a multifaceted endocrine and metabolic syndrome with complex origins and pathogenesis that has not yet been fully elucidated. Recently, the interconnection between gut microbiota and metabolic diseases has gained prominence in research, generating new insights into the correlation between PCOS and gut microbiota composition. However, the causal link between PCOS and gut microbiota remains relatively unexplored, indicating a crucial gap in current research.
METHODS
We conducted a two-sample Mendelian randomization analysis using summary statistics obtained from the MiBioGen Consortium's extensive genome-wide association studies (GWAS) meta-analysis, focusing on the gut microbiota. Summary statistics for PCOS were acquired from the FinnGen Consortium R7 release data. Various statistical approaches, including inverse variance weighted, MR-Egger, maximum likelihood, weighted model, and weighted median, have been employed to investigate the causal association between the gut microbiota and PCOS. Additionally, we performed a reverse causal analysis. Cochran's Q statistic was used to assess the heterogeneity of the instrumental variables. Regarding the relationships between PCOS and specific genera within the gut microbiota, a significance level of P < 0.05 was observed, but only when q ≥ 0.1.
RESULTS
Our analysis revealed that specific microbial genera, namely Bilophila (P = 4.62 × 10), Blautia (P = 0.02), and Holdemania (P = 0.04), displayed a protective effect against PCOS. Conversely, the presence of the Lachnospiraceae family of bacteria was associated with a detrimental effect on PCOS (P = 0.04). Furthermore, reverse Mendelian randomization analysis confirmed the significant influence of Lachnospiraceae on PCOS. No significant variations in instrumental variables or evidence of horizontal pleiotropy were observed.
CONCLUSIONS
The results revealed a definitive causal link between PCOS and the presence of Bilophila, Blautia, Holdemania, and Lachnospiraceae in the gut microbiota. This discovery could provide pivotal insights, leading to novel preventive and therapeutic approaches for PCOS.
PubMed: 38125500
DOI: 10.1016/j.heliyon.2023.e22155 -
RSC Advances Nov 2020Tributyltin (TBT), an environmental pollutant widely used in antifouling coatings, can cause multiple-organ toxicity and gut microbiome dysbiosis in organisms, and can...
Tributyltin (TBT), an environmental pollutant widely used in antifouling coatings, can cause multiple-organ toxicity and gut microbiome dysbiosis in organisms, and can even cause changes in the host metabolomic profiles. However, little is known about the underlying effects and links of TBT-induced metabolic changes and gut microbiome dysbiosis. In this study, rats were exposed to TBT at a dose of 100 μg kg body weight (BW) for 38 days, followed by multi-omics analysis, including microbiome, metabolomics, and metallomics. Results showed that TBT exposure reduced rat weight gain and decreased the serum triglyceride (TG) level. Metabolic analysis revealed that TBT fluctuated linoleic acid metabolism and glycerophospholipid metabolism in the liver; the tricarboxylic acid cycle (TCA cycle), nicotinate and nicotinamide metabolism, and arachidonic acid metabolism in serum; glycine, serine, and threonine metabolism, the one carbon pool by folate, nicotinate, and nicotinamide metabolism; and tryptophan metabolism in feces. Furthermore, TBT treatment dictated liver inflammation due to enhancing COX-2 expression by activating protein kinase R-like ER kinase (PERK) and C/EBP homologous protein (CHOP) to induce endoplasmic reticulum (ER) stress instead of stimulating arachidonic acid metabolism. Meanwhile, alteration of the intestinal flora , , , , , , and under TBT exposure were found to be involved in further mediating liver inflammation, causing lipid metabolism abnormalities, such as TG, linoleic acid, and glycerophospholipids, and interfering with the energy supply process. Among these, , , and could be considered as potential biomarkers for TBT exposure based on receiver operator characteristic (ROC) curve analysis.
PubMed: 35519721
DOI: 10.1039/d0ra07502g -
Heliyon Nov 2023Recent studies have shown altered gut microbiome composition in patients with scoliosis. However, the causal effect of gut microbiota on scoliosis remains unknown.
BACKGROUND
Recent studies have shown altered gut microbiome composition in patients with scoliosis. However, the causal effect of gut microbiota on scoliosis remains unknown.
METHODS
A Mendelian randomization (MR) study was conducted to quantify the impact of 191 gut microbiome taxa's instrumental variables from the MibioGen Genome-wide association study (GWAS) on scoliosis risk using data from the FinnGen GWAS (1168 cases and 16,4682 controls). Inverse variance weighted (IVW) was the main method, and MR results were verified by sensitive analysis.
RESULTS
(eligens group), 9, and 2 were discovered to have a protective effect on the risk of scoliosis. UCG009, , 2, (ventriosum group), (FCS020 group), 6, and RF9 may increase the occurrence of scoliosis. Heterogeneity (P > 0.05) and pleiotropy (P > 0.05) analysis confirmed the robustness of the MR results.
CONCLUSION
Our study identified four protective bacteria taxa on scoliosis and seven microbiota that may increase scoliosis occurrence. Further MR analysis is required to corroborate our findings, using a more sophisticated technique to obtain estimates with less bias and greater precision or GWAS summary data with more gut microbiome and scoliosis patients.
PubMed: 37964843
DOI: 10.1016/j.heliyon.2023.e21654