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Nature Medicine Nov 2023Genome-wide association studies (GWASs) have provided numerous associations between human single-nucleotide polymorphisms (SNPs) and health traits. Likewise,...
Genome-wide association studies (GWASs) have provided numerous associations between human single-nucleotide polymorphisms (SNPs) and health traits. Likewise, metagenome-wide association studies (MWASs) between bacterial SNPs and human traits can suggest mechanistic links, but very few such studies have been done thus far. In this study, we devised an MWAS framework to detect SNPs and associate them with host phenotypes systematically. We recruited and obtained gut metagenomic samples from a cohort of 7,190 healthy individuals and discovered 1,358 statistically significant associations between a bacterial SNP and host body mass index (BMI), from which we distilled 40 independent associations. Most of these associations were unexplained by diet, medications or physical exercise, and 17 replicated in a geographically independent cohort. We uncovered BMI-associated SNPs in 27 bacterial species, and 12 of them showed no association by standard relative abundance analysis. We revealed a BMI association of an SNP in a potentially inflammatory pathway of Bilophila wadsworthia as well as of a group of SNPs in a region coding for energy metabolism functions in a Faecalibacterium prausnitzii genome. Our results demonstrate the importance of considering nucleotide-level diversity in microbiome studies and pave the way toward improved understanding of interpersonal microbiome differences and their potential health implications.
Topics: Humans; Gastrointestinal Microbiome; Body Mass Index; Polymorphism, Single Nucleotide; Genome-Wide Association Study; Microbiota; Bacteria
PubMed: 37919437
DOI: 10.1038/s41591-023-02599-8 -
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 -
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 -
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 -
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 -
Neurology and Therapy Oct 2023The causal association between the gut microbiome and the risk of intracranial aneurysm (IA), subarachnoid hemorrhage (SAH), and unruptured aneurysm (uIA) is unclear.
INTRODUCTION
The causal association between the gut microbiome and the risk of intracranial aneurysm (IA), subarachnoid hemorrhage (SAH), and unruptured aneurysm (uIA) is unclear.
METHODS
The single nucleotide polymorphisms concerning gut microbiome were retrieved from the gene-wide association study (GWAS) of the MiBioGen consortium. The summary-level datasets of IA and SAH were obtained from the GWAS meta-analysis of the International Stroke Genetics Consortium (ISGC). Inverse variance weighting (IVW) was utilized as the primary method, complemented with sensitivity analyses for pleiotropy and increasing robustness.
RESULTS
Five, seven, and six bacterial traits were found to have a causal effect on IA, SAH, and uIA, respectively (IVW, all P < 0.05). Family.Porphyromonadaceae and genus.Bilophila were common protective bacterial features for both SAH and uIA. The heterogeneity and pleiotropy analyses confirmed the robustness of IVW results.
CONCLUSION
Our study demonstrates that gut microbiomes may exert therapeutic effects on IA, uIA, and SAH, providing clinical implications for the development of novel biomarkers and therapeutic targets.
PubMed: 37440166
DOI: 10.1007/s40120-023-00525-1 -
Investigative Ophthalmology & Visual... Jun 2023To explore the mechanisms relating the gut microbiome (GM) to age-related macular degeneration (AMD), as they remain unclear. GM taxa that appear to act within the...
PURPOSE
To explore the mechanisms relating the gut microbiome (GM) to age-related macular degeneration (AMD), as they remain unclear. GM taxa that appear to act within the gut-retina axis may affect the risk of AMD.
METHODS
Single-nucleotide polymorphisms (SNPs) of 196 GM taxa were obtained from the MiBioGen consortium, and a Mendelian randomization (MR) study was carried out to estimate the causality between GM taxa and AMD (defined as an endpoint based on ICD-9 and ICD-10). Using the data from the FinnGen consortium (6157 patients and 288,237 controls), we explored the GM taxa for causality and verified the results at the replication stage based on the MRC-IEU consortium (3553 cases and 147,089 controls). Inverse variance weighting (IVW) was the main method used to analyze causality, and the MR results were verified using heterogeneity tests and pleiotropy tests.
RESULTS
According to the MR results, order Rhodospirillales (P = 3.38 × 10-2), family Victivallaceae (P = 3.14 × 10-2), family Rikenellaceae (P = 3.58 × 10-2), genus Slackia (P = 3.15 × 10-2), genus Faecalibacterium (P = 3.01 × 10-2), genus Bilophila (P = 1.11 × 10-2), and genus Candidatus Soleaferrea (P = 2.45 × 10-2) were suggestively associated with AMD. In the replication stage, only order Rhodospirillales (P = 0.03) passed validation. The heterogeneity (P > 0.05) and pleiotropy (P > 0.05) tests in two stages confirmed the robustness of the MR results.
CONCLUSIONS
We confirmed that order Rhodospirillales influenced the risk of AMD based on the gut-retina axis, providing new impetus for the development of the GM as an intervention to prevent the occurrence and development of AMD.
Topics: Humans; Gastrointestinal Microbiome; Macular Degeneration; Retina; Causality; Actinobacteria
PubMed: 37314756
DOI: 10.1167/iovs.64.7.22 -
International Journal of Molecular... May 2023The gut-liver axis may provide a new perspective for treating anti-tuberculosis drug-induced liver injury (ATDILI). Herein, the protective effect of (Lc) was...
The gut-liver axis may provide a new perspective for treating anti-tuberculosis drug-induced liver injury (ATDILI). Herein, the protective effect of (Lc) was investigated by modulating gut microflora (GM) and the toll like receptor 4 (TLR4)-nuclear factor (NF)-κB-myeloiddifferentiationfactor 88 (MyD88) pathway. C57BL/6J mice were given three levels of Lc intragastrically for 2 h before administering isoniazid and rifampicin for 8 weeks. Blood, liver, and colon tissues, as well as cecal contents, were collected for biochemical and histological examination, as well as Western blot, quantitative real time polymerase chain reaction (qRT-PCR), and 16S rRNA analyses. Lc intervention decreased alkaline phosphatase (ALP), superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and tumor necrosis factor (TNF)-α levels ( < 0.05), recovered hepatic lobules, and reduced hepatocyte necrosis to alleviate liver injury induced by anti-tuberculosis drugs. Moreover, Lc also increased the abundance of and and decreased abundance, while enhancing zona occludens (ZO)-1 and claudin-1 protein expression compared with the model group ( < 0.05). Furthermore, Lc pretreatment reduced the lipopolysaccharide (LPS) level and downregulated NF-κB and MyD88 protein expression ( < 0.05), thus restraining pathway activation. Spearman correlation analysis indicated that and were positively correlated with ZO-1 or occludin protein expression and negatively correlated with pathway protein expression. had significant negative relationships with alanine aminotransferase (ALT) and LPS levels. In contrast, had negative associations with ZO-1, occludin, and claudin-1 protein expressions and positive correlations with LPS and pathway proteins. The results prove that can enhance the intestinal barrier and change the composition of the gut microflora. Moreover, may also inhibit TLR4-NF-κB-MyD88 pathway activation and alleviate ATDILI.
Topics: Mice; Animals; NF-kappa B; Lipopolysaccharides; Lacticaseibacillus casei; Toll-Like Receptor 4; Signal Transduction; Antitubercular Agents; Gastrointestinal Microbiome; Myeloid Differentiation Factor 88; Occludin; Claudin-1; RNA, Ribosomal, 16S; Mice, Inbred C57BL; Tumor Necrosis Factor-alpha; Chemical and Drug Induced Liver Injury; Glutathione
PubMed: 37298396
DOI: 10.3390/ijms24119444 -
Neurology International Jun 2023(1) Background: Parkinson's disease (PD) is a relatively common and complex pathology, and some of its mechanisms remain to be elucidated. Change in host microbiota is... (Review)
Review
(1) Background: Parkinson's disease (PD) is a relatively common and complex pathology, and some of its mechanisms remain to be elucidated. Change in host microbiota is related to the pathophysiology of numerous diseases. This systematic review aims to gather existing data on the occidental hemisphere, compare it, and search for any significant association between Parkinson's disease and gut microbiota dysbiosis. (2) Methods: Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) and Meta-analyses Of Observational Studies in Epidemiology (MOOSE) protocols were used for this systematic review. PubMed was used as the database search engine. Of the 166 studies found, only 10 were used, as they met our inclusion criteria: case-control studies, studies that assessed the correlation of PD and gut microbiome, studies that took place in occidental regions, and studies that were performed on humans and were written in English. The Newcastle-Ottawa Scale was used as the assessment tool for overall risk of bias in this systematic review. (3) Results: The studies analyzed were divided into three geographic areas: Region 1: United States of America and Canada; Region 2: Germany, Ireland, and Finland; and Region 3: Italy; based on geographical similarities among these populations. The following statistically significant results were described in PD patients, compared with non-PD controls. In the first region, a significant increase in the following bacteria was seen: 1. Phylum: Actinobacteriota and its Genus: ; 2. Phylum: Verrucomicrobiota and its Genus: ; 3. Genus: , , , and of the Phylum: Firmicutes; 4. Family: of Phylum: Firmicutes; 5. Phylum: Bacteroidetes and its Genus: ; 6. Phylum: Proteobacteria. A significant decrease was described in the Family: and its Genus: , , and , which belong to the Phylum: Firmicutes. In the second region, a raised number of: 1. Phylum: Verrucomicrobiota, its Genus: , and its Species: ; 2. Family: of the Phylum: Verrucomicrobiota; 3. Genus: and of the Phylum: Firmicutes; 4. Family: of the Phylum: Firmicutes; 5. Family: of the Phylum: Bacteroidetes; 6. Genus: of the Phylum: Actinobacteriota; 7. Species: of the Phylum: Thermodesulfobacteriota, was identified. Only one Genus: of the Phylum: Bacteroidetes was decreased. In the third and last region, an augmented number of these bacteria were found: 1. Phylum: Verrucomicrobiota and its Genus: ; 2. Family: and of the Phylum: Actinobacteriota; 3. Phylum: Firmicutes and its Family: and ; 4. Family: and its Genus: , of the Phylum: Firmicutes; 5. Genus: and , of the Phylum: Firmicutes; 6. Phylum: Proteobacteria, its Family: , and the Genus: , , , and ; 7. Genus: of the Phylum: Bacteroidetes. In contrast, a significant decrease in 1. Phylum: Firmicutes, its Family: , and its Genus: and 2. Genus: of the Phylum: Firmicutes, was described. (4) Conclusion: A significant gut dysbiosis, involving multiple bacterial taxa, was found in PD patients compared to healthy people in the occidental regions. However, more studies are needed to find the precise pathophysiologic involvement of other groups of pathogens, such as fungi and parasites, in the development and progression of PD.
PubMed: 37368331
DOI: 10.3390/neurolint15020047 -
Scientific Reports Jun 2023Emerging evidence suggests that plant-based fiber-rich diets improve ageing-associated health by fostering a healthier gut microbiome and microbial metabolites. However,...
Emerging evidence suggests that plant-based fiber-rich diets improve ageing-associated health by fostering a healthier gut microbiome and microbial metabolites. However, such effects and mechanisms of resistant starches from dietary pulses remain underexplored. Herein, we examine the prebiotic effects of dietary pulses-derived resistant starch (RS) on gut metabolome in older (60-week old) mice carrying a human microbiome. Gut metabolome and its association with microbiome are examined after 20-weeks feeding of a western-style diet (control; CTL) fortified (5% w/w) with RS from pinto beans (PTB), black-eyed-peas (BEP), lentils (LEN), chickpeas (CKP), or inulin (INU; reference control). NMR spectroscopy-based untargeted metabolomic analysis yield differential abundance linking phenotypic differences in specific metabolites among different RS groups. LEN and CKP increase butyrate, while INU promotes propionate. Conversely, bile acids and cholesterol are reduced in prebiotic groups along with suppressed choline-to-trimethylamine conversion by LEN and CKP, whereas amino acid metabolism is positively altered. Multi-omics microbiome-metabolome interactions reveal an association of beneficial metabolites with the Lactobacilli group, Bacteroides, Dubosiella, Parasutterella, and Parabacteroides, while harmful metabolites correlate with Butyricimonas, Faecalibaculum, Colidextribacter, Enterococcus, Akkermansia, Odoribacter, and Bilophila. These findings demonstrate the functional effects of pulses-derived RS on gut microbial metabolism and their beneficial physiologic responses in an aged host.
Topics: Humans; Animals; Mice; Aged; Resistant Starch; Disease Models, Animal; Metabolome; Microbiota; Diet, Western; Lens Plant; Aging; Bacteroidetes
PubMed: 37386089
DOI: 10.1038/s41598-023-37036-w