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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 -
The Journal of Biological Chemistry Aug 2023The obligately anaerobic sulfite-reducing bacterium Bilophila wadsworthia is a common human pathobiont inhabiting the distal intestinal tract. It has a unique ability to...
The obligately anaerobic sulfite-reducing bacterium Bilophila wadsworthia is a common human pathobiont inhabiting the distal intestinal tract. It has a unique ability to utilize a diverse range of food- and host-derived sulfonates to generate sulfite as a terminal electron acceptor (TEA) for anaerobic respiration, converting the sulfonate sulfur to HS, implicated in inflammatory conditions and colon cancer. The biochemical pathways involved in the metabolism of the C2 sulfonates isethionate and taurine by B. wadsworthia were recently reported. However, its mechanism for metabolizing sulfoacetate, another prevalent C2 sulfonate, remained unknown. Here, we report bioinformatics investigations and in vitro biochemical assays that uncover the molecular basis for the utilization of sulfoacetate as a source of TEA (STEA) for B. wadsworthia, involving conversion to sulfoacetyl-CoA by an ADP-forming sulfoacetate-CoA ligase (SauCD), and stepwise reduction to isethionate by NAD(P)H-dependent enzymes sulfoacetaldehyde dehydrogenase (SauS) and sulfoacetaldehyde reductase (TauF). Isethionate is then cleaved by the O-sensitive isethionate sulfolyase (IseG), releasing sulfite for dissimilatory reduction to HS. Sulfoacetate in different environments originates from anthropogenic sources such as detergents, and natural sources such as bacterial metabolism of the highly abundant organosulfonates sulfoquinovose and taurine. Identification of enzymes for anaerobic degradation of this relatively inert and electron-deficient C2 sulfonate provides further insights into sulfur recycling in the anaerobic biosphere, including the human gut microbiome.
Topics: Humans; Alkanesulfonates; Bilophila; Sulfites; Sulfur; Taurine; Gastrointestinal Microbiome
PubMed: 37414148
DOI: 10.1016/j.jbc.2023.105010 -
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 -
MicrobiologyOpen Mar 2021Ulcerative colitis (UC) is a frequent type of inflammatory bowel disease, characterized by periods of remission and exacerbation. Gut dysbiosis may influence...
Ulcerative colitis (UC) is a frequent type of inflammatory bowel disease, characterized by periods of remission and exacerbation. Gut dysbiosis may influence pathophysiology and clinical response in UC. The purpose of this study was to evaluate whether gut microbiota is related to the active and remission phases of pancolitis in patients with UC as well as in healthy participants. Fecal samples were obtained from 18 patients with UC and clinical-endoscopic evidenced pancolitis (active phase n = 9 and remission phase n = 9), as well as 15 healthy participants. After fecal DNA extraction, the 16S rRNA gene was amplified and sequenced (Illumina MiSeq), operational taxonomic units were analyzed with the QIIME software. Gut microbiota composition revealed a higher abundance of the phyla Proteobacteria and Fusobacteria in active pancolitis, as compared with remission and healthy participants. Likewise, a marked abundance of the genus Bilophila and Fusobacteria were present in active pancolitis, whereas a higher abundance of Faecalibacterium characterized both remission and healthy participants. LEfSe analysis showed that the genus Roseburia and Faecalibacterium were enriched in remission pancolitis, and genera Bilophila and Fusobacterium were enriched in active pancolitis. The relative abundance of Fecalibacterium and Roseburia showed a higher correlation with fecal calprotectin, while Bilophila and Fusobacterium showed AUCs (area under the curve) of 0.917 and 0.988 for active vs. remission pancolitis. The results of our study highlight the relation of gut dysbiosis with clinically relevant phases of pancolitis in patients with UC. Particularly, Fecalibacterium, Roseburia, Bilophila, and Fusobacterium were identified as genera highly related to the different clinical phases of pancolitis.
Topics: Adult; Bacteria; Biodiversity; Colitis; Colitis, Ulcerative; DNA, Bacterial; Dysbiosis; Feces; Female; Gastrointestinal Microbiome; Healthy Volunteers; Humans; Leukocyte L1 Antigen Complex; Male; RNA, Ribosomal, 16S; Severity of Illness Index
PubMed: 33970546
DOI: 10.1002/mbo3.1181 -
Frontiers in Cellular and Infection... 2022This is the first study on gut microbiota (GM) in children affected by coronavirus disease 2019 (COVID-19). Stool samples from 88 patients with suspected severe acute...
This is the first study on gut microbiota (GM) in children affected by coronavirus disease 2019 (COVID-19). Stool samples from 88 patients with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and 95 healthy subjects were collected (admission: 3-7 days, discharge) to study GM profile by 16S rRNA gene sequencing and relationship to disease severity. The study group was divided in COVID-19 (68), Non-COVID-19 (16), and MIS-C (multisystem inflammatory syndrome in children) (4). Correlations among GM ecology, predicted functions, multiple machine learning (ML) models, and inflammatory response were provided for COVID-19 and Non-COVID-19 cohorts. The GM of COVID-19 cohort resulted as dysbiotic, with the lowest α-diversity compared with Non-COVID-19 and CTRLs and by a specific β-diversity. Its profile appeared enriched in , , and and reduced in , , , , , , and , compared with CTRLs ( 0.05). All GM paired-comparisons disclosed comparable results through all time points. The comparison between COVID-19 and Non-COVID-19 cohorts highlighted a reduction of in the COVID-19 cohort ( < 0.05). The GM of MIS-C cohort was characterized by an increase of , , , , and and a decrease of , , , and , compared with CTRLs. Stratifying for disease severity, the GM associated to "moderate" COVID-19 was characterized by lower α-diversity compared with "mild" and "asymptomatic" and by a GM profile deprived in , , , and and enriched in , , , , , , and The ML models identified , , , , , , , , , , , , , , , , and as microbial markers of COVID-19. The KEGG ortholog (KO)-based prediction of GM functional profile highlighted 28 and 39 KO-associated pathways to COVID-19 and CTRLs, respectively. Finally, and correlated with proinflammatory cytokines regardless disease severity. Unlike adult GM profiles, was a specific marker of pediatric COVID-19 GM. The durable modification of patients' GM profile suggested a prompt GM quenching response to SARS-CoV-2 infection since the first symptoms. and reduced fatty acid and amino acid degradation were proposed as specific COVID-19 disease traits, possibly associated to restrained severity of SARS-CoV-2-infected children. Altogether, this evidence provides a characterization of the pediatric COVID-19-related GM.
Topics: Adult; Bacteroides; Bifidobacterium; COVID-19; Child; Clostridium; Feces; Gastrointestinal Microbiome; Humans; RNA, Ribosomal, 16S; SARS-CoV-2; Systemic Inflammatory Response Syndrome
PubMed: 35873161
DOI: 10.3389/fcimb.2022.908492 -
International Journal of Molecular... Nov 2022The prevalence of type 2 diabetes mellitus (T2D) is alarmingly increasing worldwide, urgently calling for a better understanding of the underlying mechanisms in order to...
The prevalence of type 2 diabetes mellitus (T2D) is alarmingly increasing worldwide, urgently calling for a better understanding of the underlying mechanisms in order to step up prevention and improve therapeutic approaches. It is becoming evident that the gut microbiota seem to have an endless capacity to impact T2D. In this study, we profile the gut microbiome patterns in T2D patients from Romania, by using quantitative Real-Time PCR and next generation sequencing. We enrolled a total of 150 individuals (105 T2D patients, 50 of them without metformin treatment and 45 healthy volunteers). The levels of potentially beneficial butyrate-producing bacteria were significantly reduced, while potentially pathogenic microorganisms such as and were enriched in T2D patients. We evaluated the correlation between clinical parameters and gut microbiota and identified the genera Bacteroides, , , and as possible detrimental factors in T2D. Our findings suggest that the gut microbiota may be a potential target in novel approaches to halt the development of T2D-associated complications.
Topics: Humans; Diabetes Mellitus, Type 2; Microbiota; Metformin; Gastrointestinal Microbiome; Bacteroidetes
PubMed: 36499348
DOI: 10.3390/ijms232315023 -
Frontiers in Immunology 2023The pathogenesis of peptic ulcer diseases (PUDs) involves multiple factors, and the contribution of gut microbiota to this process remains unclear. While previous... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The pathogenesis of peptic ulcer diseases (PUDs) involves multiple factors, and the contribution of gut microbiota to this process remains unclear. While previous studies have associated gut microbiota with peptic ulcers, the precise nature of the relationship, whether causal or influenced by biases, requires further elucidation.
DESIGN
The largest meta-analysis of genome-wide association studies was conducted by the MiBioGen consortium, which provided the summary statistics of gut microbiota for implementation in the Mendelian randomization (MR) analysis. Summary statistics for five types of PUDs were compiled using the FinnGen Consortium R8 release data. Various statistical techniques, including inverse variance weighting (IVW), MR-Egger, weighted median (WM), weighted mode, and simple mode, were employed to assess the causal relationships between gut microbiota and these five PUDs.
RESULT
In the intestinal microbiome of 119 known genera, we found a total of 14 causal associations with various locations of PUDs and reported the potential pathogenic bacteria of et al. Among them, four had causal relationships with esophageal ulcer, one with gastric ulcer, three with gastroduodenal ulcer, four with duodenal ulcer, and two with gastrojejunal ulcer.
CONCLUSION
In this study, the pathogenic bacterial genera in the gut microbiota that promote the occurrence of PUDs were found to be causally related. There are multiple correlations between intestinal flora and PUDs, overlapping PUDs have overlapping associated genera. The variance in ulcer-related bacterial genera across different locations underscores the potential influence of anatomical locations and physiological functions.
Topics: Humans; Gastrointestinal Microbiome; Ulcer; Genome-Wide Association Study; Mendelian Randomization Analysis; Peptic Ulcer; Stomach Ulcer
PubMed: 37869000
DOI: 10.3389/fimmu.2023.1260780 -
Journal of Clinical Microbiology Apr 2001Bilophila wadsworthia is a common inhabitant of the human colon and has been associated with appendicitis and other local sites of inflammation in humans....
Bilophila wadsworthia is a common inhabitant of the human colon and has been associated with appendicitis and other local sites of inflammation in humans. Challenge-exposure or prevalence studies in laboratory and other animals have not been reported. B. wadsworthia is closely related phylogenetically to Desulfovibrio sp. and Lawsonia intracellularis, which are considered colon pathogens. We developed a PCR specific for B. wadsworthia DNA. Samples of bacterial DNA extracted from the feces of pigs on six farms in Australia and four farms in Venezuela were examined. Specific DNA of B. wadsworthia was detected in the feces of 58 of 161 Australian and 2 of 45 Venezuelan pigs, results comprising 100% of the neonatal pigs, 15% of the weaned grower pigs, and 27% of the adult sows tested. Single-stranded conformational polymorphism analysis of PCR product DNA derived from pigs or from known human strains showed an identical pattern. Histologic examination of the intestines of weaned B. wadsworthia-positive pigs found no or minor specific lesions in the small and large intestines, respectively. B. wadsworthia is apparently a common infection in neonatal pigs, but its prevalence decreases after weaning. The possible role of B. wadsworthia as an infection in animals and in human colons requires further study.
Topics: Animals; Colon; Colonic Diseases; DNA, Bacterial; Deltaproteobacteria; Feces; Gram-Negative Bacterial Infections; Humans; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Swine; Swine Diseases
PubMed: 11283090
DOI: 10.1128/JCM.39.4.1577-1579.2001