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Frontiers in Cellular and Infection... 2022Many individuals diagnosed with autism spectrum disorder (ASD) experience gastrointestinal (GI) dysfunction and show microbial dysbiosis. Variation in gut microbial... (Review)
Review
Many individuals diagnosed with autism spectrum disorder (ASD) experience gastrointestinal (GI) dysfunction and show microbial dysbiosis. Variation in gut microbial populations is associated with increased risk for GI symptoms such as chronic constipation and diarrhoea, which decrease quality of life. Several preclinical models of autism also demonstrate microbial dysbiosis. Given that much pre-clinical research is conducted in mouse models, it is important to understand the similarities and differences between the gut microbiome in humans and these models in the context of autism. We conducted a systematic review of the literature using PubMed, ProQuest and Scopus databases to compare microbiome profiles of patients with autism and transgenic (NL3, Shank3 KO, 15q dup), phenotype-first (BTBR) and environmental (Poly I:C, Maternal Inflammation Activation (MIA), valproate) mouse models of autism. Overall, we report changes in fecal microbial communities relevant to ASD based on both clinical and preclinical studies. Here, we identify an overlapping cluster of genera that are modified in both fecal samples from individuals with ASD and mouse models of autism. Specifically, we describe an increased abundance of , , and and a decrease in genera in both humans and rodents relevant to this disorder. Studies in both humans and mice highlighted multidirectional changes in abundance (i.e. in some cases increased abundance whereas other reports showed decreases) for several genera including , , , and , suggesting that these genera may be susceptible to modification in autism. Identification of these microbial profiles may assist in characterising underlying biological mechanisms involving host-microbe interactions and provide future therapeutic targets for improving gut health in autism.
Topics: Animals; Autism Spectrum Disorder; Autistic Disorder; Disease Models, Animal; Dysbiosis; Gastrointestinal Diseases; Gastrointestinal Microbiome; Humans; Mice; Microfilament Proteins; Nerve Tissue Proteins; Quality of Life
PubMed: 35846755
DOI: 10.3389/fcimb.2022.905841 -
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 -
Nature Communications Jul 2018Dietary lipids favor the growth of the pathobiont Bilophila wadsworthia, but the relevance of this expansion in metabolic syndrome pathogenesis is poorly understood....
Dietary lipids favor the growth of the pathobiont Bilophila wadsworthia, but the relevance of this expansion in metabolic syndrome pathogenesis is poorly understood. Here, we showed that B. wadsworthia synergizes with high fat diet (HFD) to promote higher inflammation, intestinal barrier dysfunction and bile acid dysmetabolism, leading to higher glucose dysmetabolism and hepatic steatosis. Host-microbiota transcriptomics analysis reveal pathways, particularly butanoate metabolism, which may underlie the metabolic effects mediated by B. wadsworthia. Pharmacological suppression of B. wadsworthia-associated inflammation demonstrate the bacterium's intrinsic capacity to induce a negative impact on glycemic control and hepatic function. Administration of the probiotic Lactobacillus rhamnosus CNCM I-3690 limits B. wadsworthia-induced immune and metabolic impairment by limiting its expansion, reducing inflammation and reinforcing intestinal barrier. Our results suggest a new avenue for interventions against western diet-driven inflammatory and metabolic diseases.
Topics: Animals; Bilophila; Blood Glucose; Cytokines; Desulfovibrionaceae Infections; Diet, High-Fat; Dietary Fats; Fatty Liver; Gastrointestinal Microbiome; Lacticaseibacillus rhamnosus; Liver; Liver Function Tests; Male; Metabolic Networks and Pathways; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Probiotics; Transcriptome
PubMed: 30022049
DOI: 10.1038/s41467-018-05249-7 -
BMC Microbiology Dec 2021Bilophila wadsworthia, a strictly anaerobic, sulfite-reducing bacterium and common member of the human gut microbiota, has been associated with diseases such as...
BACKGROUND
Bilophila wadsworthia, a strictly anaerobic, sulfite-reducing bacterium and common member of the human gut microbiota, has been associated with diseases such as appendicitis and colitis. It is specialized on organosulfonate respiration for energy conservation, i.e., utilization of dietary and host-derived organosulfonates, such as taurine (2-aminoethansulfonate), as sulfite donors for sulfite respiration, producing hydrogen sulfide (HS), an important intestinal metabolite that may have beneficial as well as detrimental effects on the colonic environment. Its taurine desulfonation pathway involves the glycyl radical enzyme (GRE) isethionate sulfite-lyase (IslAB), which cleaves isethionate (2-hydroxyethanesulfonate) into acetaldehyde and sulfite.
RESULTS
We demonstrate that taurine metabolism in B. wadsworthia 3.1.6 involves bacterial microcompartments (BMCs). First, we confirmed taurine-inducible production of BMCs by proteomic, transcriptomic and ultra-thin sectioning and electron-microscopical analyses. Then, we isolated BMCs from taurine-grown cells by density-gradient ultracentrifugation and analyzed their composition by proteomics as well as by enzyme assays, which suggested that the GRE IslAB and acetaldehyde dehydrogenase are located inside of the BMCs. Finally, we are discussing the recycling of cofactors in the IslAB-BMCs and a potential shuttling of electrons across the BMC shell by a potential iron-sulfur (FeS) cluster-containing shell protein identified by sequence analysis.
CONCLUSIONS
We characterized a novel subclass of BMCs and broadened the spectrum of reactions known to take place enclosed in BMCs, which is of biotechnological interest. We also provided more details on the energy metabolism of the opportunistic pathobiont B. wadsworthia and on microbial HS production in the human gut.
Topics: Bacterial Proteins; Bilophila; Cell Compartmentation; Gastrointestinal Microbiome; Gene Expression Profiling; Humans; Hydrogen Sulfide; Isethionic Acid; Proteomics; Sulfites; Taurine
PubMed: 34903181
DOI: 10.1186/s12866-021-02386-w -
Cancers Jan 2023A glycal radical enzyme called isethionate sulfite-lyase (Isla) breaks the C-S bond in isethionate to produce acetaldehyde and sulfite. This enzyme was found in the...
Multi-Fold Computational Analysis to Discover Novel Putative Inhibitors of Isethionate Sulfite-Lyase (Isla) from Combating Colorectal Cancer and Inflammatory Bowel Diseases.
A glycal radical enzyme called isethionate sulfite-lyase (Isla) breaks the C-S bond in isethionate to produce acetaldehyde and sulfite. This enzyme was found in the Gram-negative, colonial bacteria. Sulfur dioxide, acetate, and ammonia are produced by the anaerobic respiration route from (sulfonate isethionate). Strong genotoxic HS damages the colon's mucous lining, which aids in the development of colorectal cancer. HS production also contributes to inflammatory bowel diseases such as colitis. Here, we describe the structure-based drug designing for the Isla using an in-house database of naturally isolated compounds and synthetic derivatives. In structure-based drug discovery, a combination of methods was used, including molecular docking, pharmacokinetics properties evaluation, binding free energy calculations by the molecular mechanics/generalized born surface area (MM/GBSA) method, and protein structure dynamics exploration via molecular dynamic simulations, to retrieve novel and putative inhibitors for the Isla protein. Based on the docking score, six compounds show significant binding interaction with the Isla active site crucial residues and exhibit drug-like features, good absorption, distribution, metabolism, and excretion profile with no toxicity. The binding free energy reveals that these compounds have a strong affinity with the Isla. In addition, the molecular dynamics simulations reveal that these compounds substantially affect the protein structure dynamics. As per our knowledge, this study is the first attempt to discover Isla potential inhibitors. The compounds proposed in the study using a multi-fold computational technique may be verified in vitro as possible inhibitors of Isla and possess the potential for the future development of new medications that target Isla.
PubMed: 36765864
DOI: 10.3390/cancers15030901 -
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 -
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