Eubacterium Eligens Research Articles

Features of intestinal microbiota taxonomic composition and their relation with hormonal and immune status assessed in women with external genital endometriosis

Aim: systemically assessed characteristics of intestinal microbiota taxonomic composition in relation to parameters of hormonal and immune status in patients with external genital endometriosis (EGE).Materials and Methods. The controlled cross-sectional study included 33 patients with ЕGE comprising main group, and 30 healthy women enrolled to control group. All women underwent assessment of hormonal status and cytokine expression levels in peripheral blood. Level of blood hormones estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL) was carried out using enzyme-linked immunosorbent and chemiluminescent assays. Expression levels of cytokines such as interleukin (IL) IL-6, IL-8, tumor necrosis factor alpha (TNF-α) were analyzed by an enzyme-linked immunosorbent assay. Taxonomic composition of intestinal microbiota at the level of phyla and genera was carried out by 16S ribosomal RNA genesequencing. Microbial community α-diversity, the Chao1, ACE, and Sobs indices were used.Results. The concentration of blood E2 in main group was significantly higher compared to control group. Also, women with ЕGE had higher plasma concentrations for IL-6, IL-8, IL-17 and TNF-α compared to those in control group (p < 0.001). While analyzing bacterial community α-diversity in main group, Chao1 index was found to be significantly decreased. At the phylum level, the Firmicutes/Bacteroidetes ratio was increased in patients with ЕGE compared with that in control group. Among the 20 largest genera in patients with ЕGE, significant abundance was observed for Lachnospira, Blautia, Dorea, Streptococcus, Eubacterium hallii_group paralleled with significant decline in Bifidobacterium and Eubacterium eligens_group. A positive correlation was obtained between estrogen levels and the number of representatives from the genera Eubacterium hallii_group and Streptococcus, IL-8 and Streptococcus, TNF-α and Streptococcus and Lachnospira, as well as a negative correlation between TNF-α and Bifidobacterium.Conclusion. A relation between dysbiotic intestinal alterations and developing endometriosis was found. The identified correlations between altered taxonomic composition of the intestinal microflora and parameters of hormonal and immune status in patients with ЕGE suggest that intestinal microbiota is involved in pathophysiology of endometriosis.

Exploring gut microbiota's role in rheumatic valve disease: insights from a Mendelian randomization study and mediation analysis.

Investigating the relationship between gut microbiota and Rheumatic Valve Disease (RVD) is crucial for understanding the disease's etiology and developing effective interventions. Our study adopts a novel approach to examine the potential causal connections between these factors. Utilizing a two-sample Mendelian Randomization (MR) framework, we incorporated a multi-variable MR (MVMR) strategy to assess the mediatory mechanisms involved. This approach involved analyzing data from the MiBioGen consortium for gut microbiota and the FinnGen for RVD, among other sources. Instrumental variables (IVs) were carefully selected based on rigorous MR principles, and statistical analysis was conducted using bidirectional two-sample MR, such as inverse variance-weighted (IVW), weighted median, MR-Egger regression and MR Steiger Test methods. The MR-PRESSO strategy was employed for outlier detection, and MVMR was used to untangle the complex relationships between multiple microbiota and RVD. Our analysis highlighted several gut microbiota classes and families with potential protective effects against RVD, including Lentisphaerae, Alphaproteobacteria, and Streptococcaceae. In contrast, certain genera, such as Eubacterium eligens and Odoribacter, were identified as potential risk factors. The MVMR analysis revealed significant mediation effects of various immune cell traits and biomarkers, such as CD4-CD8- T cells, CD3 on Terminally Differentiated CD8+ T cell and Pentraxin-related protein PTX, elucidating the complex pathways linking gut microbiota to RVD. This study underscores the intricate and potentially causal relationship between gut microbiota and RVD, mediated through a range of immune and hormonal factors. The use of MVMR in our methodological approach provides a more comprehensive understanding of these interactions, highlighting the gut microbiota's potential as therapeutic targets in RVD management. Our findings pave the way for further research to explore these complex relationships and develop targeted interventions for RVD.

Sourdough bread enriched with exopolysaccharides and gazpacho by-products modulates in vitro the microbiota dysbiosis

Sourdough bread enriched with soluble fiber (by in-situ exopolysaccharides production) and insoluble fiber (by gazpacho by-products addition) showed prebiotic effects an in vitro dynamic colonic fermentation performance with obese volunteer's microbiota. Bifidobacterium population was maintained whereas Lactobacillus increased throughout the colonic sections. Conversely, Enterobacteriaceae and Clostridium groups clearly decreased.Specific bacteria associated with beneficial effects increased in the ascending colon (Lactobacillus fermentum, Lactobacillus paracasei, Bifidobacterium longum and Bifidobacterium adolescentis) whereas Eubacterium eligens, Alistipes senegalensis, Prevotella copri and Eubacterium desmolans increased in the transversal and descending colon. Additionally, Blautia faecis and Ruminococcus albus increased in the transversal colon, and Bifidobacterium longum, Roseburia faecis and Victivallis vadensis in the descending colon.Bifidobacterium and Lactobacillus fermented the in-situ exopolysaccharides and released pectins from gazpacho by-products, as well as cellulosic degraded bacteria. This increased the short and medium chain fatty acids. Acetic acid, as well as butyric acid, increased throughout the colonic tract, which showed greater increases only in the transversal and descending colonic segments. Conversely, propionic acid was slightly affected by the colonic fermentation.These results show that sourdough bread is a useful food matrix for the enrichment of vegetable by-products (or other fibers) in order to formulate products with microbiota modulatory capacities.

Alteration in gut microbial characteristics of patients with acromegaly.

Studies on intestinal microbiota in acromegaly are scant. This study aimed to characterize the gut microbiome in patients with acromegaly. Stool samples were collected from 11 patients newly diagnosed with acromegaly and 12 healthy controls matched for body mass index (BMI) and age after three days on a standard diet. Clinical and gut microbial composition assessments were performed for the two participant groups using 16S rRNA gene amplicon sequencing. There was no difference in the alpha diversity of the microbiota between the samples from patients with acromegaly and those from the healthy controls. Based on beta diversity measurements, differences in microbial community structures were found to be significant only when compared using the Jaccard similarity index. The corresponding Firmicutes/Bacteroidota ratio tended to be higher in individuals with acromegaly than in healthy controls. The mean relative abundance of Actinobacteriota was 2.3 times higher in the acromegaly patient group than in the control group. Eggerthellaceae, Christensenellaceae, and Bacteroidaceae were among the significantly abundant bacterial families in the samples from the acromegaly patient group, while Butyricicoccaceae and Tannerellaceae were decreased. At the level of the genus, the most discriminative features were the abundance of Prevotella 7, Bacteroides, Senegalimassilia, Enterohabdus, the Family XIII AD3011 group, Howardella, and Hungatella in the samples from the acromegaly patient group. In contrast, the Butyrivibrio and the Eubacterium eligens group were the most discriminative genera for the healthy controls and were significantly less abundant in patients with acromegaly. While there were no significantly differentiated taxa between the diabetic and non-diabetic subgroups, Prevotella_7 was significantly enriched in the osteoarthritis (OA) subgroup. No significant association was found between individual genera and growth hormone (GH) levels and insulin-like growth factor-1 (IGF-1) levels as well as the upper limit of normal (ULN). Although alpha and beta diversity were mainly similar between the two groups, significant differences were observed between the acromegaly group and the control group at the family and genus levels. These results suggest that the differences between the microbial communities in patients with acromegaly and those in healthy individuals consist primarily of compositional differences independent of abundance. Prospective studies are needed to further explore the clinical implications of gut microbiome dysbiosis in patients with acromegaly.

Genetically determined gut microbiota associates with pulmonary arterial hypertension: a Mendelian randomization study

BackgroundEmerging evidences have demonstrated that gut microbiota composition is associated with pulmonary arterial hypertension (PAH). However, the underlying causality between intestinal dysbiosis and PAH remains unresolved.MethodAn analysis using the two-sample Mendelian randomization (MR) approach was conducted to examine the potential causal relationship between gut microbiota and PAH. To assess exposure data, genetic variants associated with 196 bacterial traits were extracted from the MiBioGen consortium, which included a sample size of 18,340 individuals. As for the outcomes, summary statistics for PAH were obtained from the NHGRI-EBI GWAS Catalog, which conducted a meta-analysis of four independent studies comprising a total of 11,744 samples. Causal effects were estimated employing various methods, including inverse variance weighted (IVW), MR-Egger, weighted median, weight mode and simple mode, with sensitivity analyses also being implemented with Cochran’s Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and funnel plots.ResultsFollowing false discovery rate (FDR) correction, the genetically predicted genus Eubacterium fissicatena group (odds ratio (OR) 1.471, 95% confidence interval (CI) 1.178–1.837, q = 0.076) exhibited a causal association with PAH. In addition, the genus LachnospiraceaeUCG004 (OR 1.511, 95% CI 1.048–2.177) and genus RuminococcaceaeUCG002 (OR 1.407, 95% CI 1.040–1.905) showed a suggestive increased risk of PAH, while genus Eubacterium eligens group (OR 0.563, 95% CI 0.344–0.922), genus Phascolarctobacterium (OR 0.692, 95% CI 0.487–0.982), genus Erysipelatoclostridium (OR 0.757, 95% CI 0.579–0.989) and genus T–yzzerella3 (OR 0.768, 95% CI 0.624–0.945) were found to have nominal protective effect against PAH.ConclusionThe findings from our MR study have revealed a potential causal relationship between gut microbiota and PAH. Specifically, we have identified four types of gut microbiota that exhibit a protective effect on PAH, as well as three types that have a detrimental impact on PAH, thereby offering valuable insights for future mechanistic and clinical investigations in the field of PAH.

Integrative metagenomic analysis reveals distinct gut microbial signatures related to obesity

Obesity is a metabolic disorder closely associated with profound alterations in gut microbial composition. However, the dynamics of species composition and functional changes in the gut microbiome in obesity remain to be comprehensively investigated. In this study, we conducted a meta-analysis of metagenomic sequencing data from both obese and non-obese individuals across multiple cohorts, totaling 1351 fecal metagenomes. Our results demonstrate a significant decrease in both the richness and diversity of the gut bacteriome and virome in obese patients. We identified 38 bacterial species including Eubacterium sp. CAG:274, Ruminococcus gnavus, Eubacterium eligens and Akkermansia muciniphila, and 1 archaeal species, Methanobrevibacter smithii, that were significantly altered in obesity. Additionally, we observed altered abundance of five viral families: Mesyanzhinovviridae, Chaseviridae, Salasmaviridae, Drexlerviridae, and Casjensviridae. Functional analysis of the gut microbiome indicated distinct signatures associated to obesity and identified Ruminococcus gnavus as the primary driver for function enrichment in obesity, and Methanobrevibacter smithii, Akkermansia muciniphila, Ruminococcus bicirculans, and Eubacterium siraeum as functional drivers in the healthy control group. Additionally, our results suggest that antibiotic resistance genes and bacterial virulence factors may influence the development of obesity. Finally, we demonstrated that gut vOTUs achieved a diagnostic accuracy with an optimal area under the curve of 0.766 for distinguishing obesity from healthy controls. Our findings offer comprehensive and generalizable insights into the gut bacteriome and virome features associated with obesity, with the potential to guide the development of microbiome-based diagnostics.

Gut microbiome alterations at acute myeloid leukemia diagnosis are associated with muscle weakness and anorexia.

The gut microbiota makes critical contributions to host homeostasis, and its role in the treatment of acute myeloid leukemia (AML) has attracted attention. We investigated whether the gut microbiome is affected by AML, and whether such changes are associated with hallmarks of cachexia. Biological samples and clinical data were collected from 30 antibiotic- free AML patients at diagnosis and matched volunteers (1:1) in a multicenter, cross-sectional, prospective study. The composition and functional potential of the fecal microbiota were analyzed using shotgun metagenomics. Fecal, blood, and urinary metabolomics analyses were performed. AML patients displayed muscle weakness, anorexia, signs of altered gut function, and glycemic disorders. The composition of the fecal microbiota differed between patients with AML and control subjects, with an increase in oral bacteria. Alterations in bacterial functions and fecal metabolome support an altered redox status in the gut microbiota, which may contribute to the altered redox status observed in patients with AML. Eubacterium eligens, reduced 3-fold in AML patients, was strongly correlated with muscle strength and citrulline, a marker of enterocyte mass and function. Blautia and Parabacteroides, increased in patients with AML, were correlated with anorexia. Several bacterial taxa and metabolites (e.g., Blautia, Prevotella, phenylacetate, and hippurate) previously associated with glycemic disorders were altered. Our work revealed important perturbations in the gut microbiome of AML patients at diagnosis, which are associated with muscle strength, altered redox status, and anorexia. These findings pave the way for future mechanistic work to explore the function and therapeutic potential of the bacteria identified in this study.

Plant-based diets and the gut microbiome: findings from the Baltimore Longitudinal Study of Aging

BackgroundMounting evidence indicates that although some plant-based diets are healthful, others are not. Changes in the gut microbiome and microbiome-dependent metabolites, such as trimethylamine N-oxide (TMAO), may explain differential health effects of plant-based diets. However, human data are sparse on whether qualitatively distinct types of plant-based diets differentially affect gut microbiome diversity, composition, particularly at the species level, and/or metabolites. ObjectivesWe aimed to examine cross-sectional associations of different plant-based indices with adult gut microbiome diversity, composition, and the metabolite TMAO. MethodsWe studied 705 adults in the Baltimore Longitudinal Study of Aging with data for diet, fecal microbiome (shotgun metagenomic sequencing), and key covariates. We derived healthful plant-based diet index (hPDI) and unhealthful plant-based diet index (uPDI) using data from food frequency questionnaires. We examined plant-based diet indices with microbiome α-diversity (richness and evenness measures), β-diversity (Bray–Curtis and UniFrac measures), composition (species level), and plasma TMAO. We used regression models to determine associations before and after adjustment for age, sex, education, physical activity, smoking status, body mass index, and total energy intake. ResultsThe analytic sample (mean age, 71.0 years, SD = 12.8 years) comprised 55.6% female and 67.5% non-Hispanic White participants. hPDI was positively and uPDI negatively associated with microbiome α-diversity, driven by microbial evenness (Pielou P < 0.05). hPDI was also positively associated with relative abundance of 3 polysaccharide-degrading bacterial species (Faecalibacterium prausnitzii, Eubacterium eligens, and Bacteroides thetaiotaomicron) and inversely associated with 6 species (Blautia hydrogenotrophica, Doreasp CAG 317, Eisenbergiella massiliensis, Sellimonas intestinalis, Blautia wexlerae, and Alistipes shahii). Furthermore, hPDI was inversely associated with TMAO. Associations did not differ by age, sex, or race. ConclusionsGreater adherence to a healthful plant-based diet is associated with microbiome features that have been linked to positive health; adherence to an unhealthful plant-based diet has opposing or null associations with these features.

Genetic causal association between gut microbiota and sepsis: Evidence from a two-sample bidirectional Mendelian randomization analysis

BackgroundSepsis is a severe and potentially life-threatening condition characterized by a dysregulated host response and organ dysfunction. The causal relationship between intestinal microbiota and sepsis is unclear. MethodsA two-sample Mendelian randomization (MR) study was performed to proxy the causal association between gut microbiota and sepsis. The genome-wide association study (GWAS) data of sepsis and gut microbiome were collected from the Integrative Epidemiology Unit (IEU) OpenGWAS, with summary-level data obtained from the UK Biobank. Five traditional methods were used to estimate the potential causal relationships between gut microbiota and sepsis, including the inverse-variance weighted method, weighted median method, MR-Egger regression, simple mode, and weighted mode. Reverse MR analysis was performed on the bacteria that were found to be causally associated with sepsis in forward MR analysis. Cochran's Q statistic was used to quantify the heterogeneity of instrumental variables. ResultsThe inverse-variance weighted estimate suggested that class Lentisphaeria (odds ratio [OR]=0.86, 95% confidence interval [CI]: 0.78 to 0.94, P=0.0017, q=0.1596) and order Victivallales (OR=0.86, 95% CI: 0.78 to 0.94, P=0.0017, q=0.1596) have a protective effect on sepsis. The genus Eubacterium eligens group (OR=1.34, 95% CI: 1.11 to 1.63, P=0.0029, q=0.1881) was positively associated with the risk of sepsis. Sepsis may be a significant risk factor for genus Odoribacter (OR=1.18, 95% CI: 1.10 to 1.39, P=0.0415, q=0.9849) and Phascolarctobacterium (OR=1.21, 95% CI: 1.00 to 1.46, P=0.0471, q=0.9849), but this effect was not statistically significant after false discovery rate correction. There was a suggestive association between sepsis and Faecalibacterium (OR=0.85, 95% CI: 0.73 to 0.98, P=0.0278) and Ruminococcus 1 (OR=0.85, 95% CI: 0.73 to 1.00, P=0.0439), which were not significant after false discovery rate correction (q>0.2). ConclusionsThis study found that class Lentisphaeria, order Victivallales, and genus Eubacterium eligens group may have a causal relationship with the risk of sepsis.

Identification of bidirectional causal links between gut microbiota and narcolepsy type 1 using Mendelian randomization.

Narcolepsy type 1 (NT1), characterized by cataplexy and orexin deficiency, is a rare and frequently debilitating neurological disorder. It has been noted to have connections with the gut microbiota, yet the exact causal relationships remain unclear. We conducted a comprehensive bidirectional Mendelian randomization (MR) study to rigorously investigate the causal links between the gut microbiota and NT1, utilizing genetic datasets from the MiBioGen consortium and FinnGen consortium, respectively. The inverse-variance weighted (IVW) method was employed to obtain the primary MR estimates, supplemented by several alternative methods as well as sensitivity analyses including Cochran's Q, MR-Egger, MR pleiotropy residual sum and outlier, leave-one-out, and genetic colocalization. Our findings indicated that an increased relative abundance of five genera including Blautia (p = 4.47E-5), Collinsella (p = 0.036), Gordonibacter (p = 0.047), Hungatella (p = 0.015), and Lachnospiraceae UCG010 (p = 0.027) may be associated with a decreased risk of NT1. Conversely, an increased relative abundance of class Betaproteobacteria (p = 0.032), genus Alloprevotella (p = 0.009), and genus Ruminiclostridium6 (p = 0.029) may potentially heighten the risk of NT1. The onset of NT1 may lead to a decrease in the relative abundance of genus Eubacterium eligens group (p = 0.022), while a increase in the family Family XI (p = 0.009), genus Hungatella (p = 0.005), genus Prevotella (p = 0.013), and unknown genus id.2001 (p = 0.019). These findings remained robust under all sensitivity analyses. Our results offer robust evidence for the bidirectional causal links between particular gut microbial taxa and NT1, underscoring the significance of the microbiota-gut-brain axis in the pathological process of NT1.

Genetic evidence supporting the causal role of gut microbiota in chronic kidney disease and chronic systemic inflammation in CKD: a bilateral two-sample Mendelian randomization study.

The association of gut microbiota (GM) and chronic kidney disease (CKD), and the relevancy of GM and chronic systemic inflammation in CKD, were revealed on the basis of researches on gut-kidney axis in previous studies. However, their causal relationships are still unclear. To uncover the causal relationships between GM and CKD, as well as all known GM from eligible statistics and chronic systemic inflammation in CKD, we performed two-sample Mendelian randomization (MR) analysis. We acquired the latest and most comprehensive summary statistics of genome-wide association study (GWAS) from the published materials of GWAS involving GM, CKD, estimated glomerular filtration rate (eGFR), c-reactive protein (CRP) and urine albumin creatine ratio (UACR). Subsequently, two-sample MR analysis using the inverse-variance weighted (IVW) method was used to determine the causality of exposure and outcome. Based on it, additional analysis and sensitivity analysis verified the significant results, and the possibility of reverse causality was also assessed by reverse MR analysis during this study. At the locus-wide significance threshold, IVW method and additional analysis suggested that the protective factors for CKD included family Lachnospiraceae (P=0.049), genus Eubacterium eligens group (P=0.002), genus Intestinimonas (P=0.009), genus Streptococcu (P=0.003) and order Desulfovibrionales (P=0.001). Simultaneously, results showed that genus LachnospiraceaeUCG010 (P=0.029) was a risk factor for CKD. Higher abundance of genus Desulfovibrio (P=0.048) was correlated with higher eGFR; higher abundance of genus Parasutterella (P=0.018) was correlated with higher UACR; higher abundance of class Negativicutes (P=0.003), genus Eisenbergiella (P=0.021), order Selenomonadales (P=0.003) were correlated with higher CRP levels; higher abundance of class Mollicutes (0.024), family Prevotellaceae (P=0.030), phylum Tenericutes (P=0.024) were correlated with lower levels of CRP. No significant pleiotropy or heterogeneity was found in the results of sensitivity analysis, and no significant causality was found in reverse MR analysis. This study highlighted associations within gut-kidney axis, and the causal relationships between GM and CKD, as well as GM and chronic systemic inflammation in CKD were also revealed. Meanwhile, we expanded specific causal gut microbiota through comprehensive searches. With further studies for causal gut microbiota, they may have the potential to be new biomarkers for targeted prevention of CKD and chronic systemic inflammation in CKD.

Causal relationship between gut microbiota with subcutaneous and visceral adipose tissue: a bidirectional two-sample Mendelian Randomization study.

Numerous studies have revealed associations between gut microbiota and adipose tissue. However, the specific functional bacterial taxa and their causal relationships with adipose tissue production in different regions of the body remain unclear. We conducted a bidirectional two-sample Mendelian Randomization (MR) study using aggregated data from genome-wide association studies (GWAS) for gut microbiota and adipose tissue. We employed methods such as inverse variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode to assess the causal relationships between gut microbiota and subcutaneous adipose tissue (SAT) as well as visceral adipose tissue (VAT). Cochran's Q test, MR-Egger regression intercept analysis, and MR-PRESSO were used to test for heterogeneity, pleiotropy, and outliers of the instrumental variables, respectively. Reverse MR was employed to evaluate the reverse causal relationships between SAT, VAT, and gut microbiota with significant associations. IVW results demonstrated that Betaproteobacteria were protective factors for SAT production (OR = 0.88, 95% CI: 0.80-0.96, p = 0.005) and VAT production (OR = 0.91, 95% CI: 0.83-0.99, p = 0.030). Various bacterial taxa including Ruminococcaceae UCG002 (OR = 0.94, 95% CI: 0.89-0.99, p = 0.017), Methanobacteria class (OR = 0.96, 95% CI: 0.92-1.00, p = 0.029), and Burkholderiales (OR = 0.90, 95% CI: 0.83-0.98, p = 0.012) were associated only with decreased SAT production. Rikenellaceae RC9 gut group (OR = 1.05, 95% CI: 1.02-1.10, p = 0.005), Eubacterium hallii group (OR = 1.08, 95% CI: 1.01-1.15, p = 0.028), Peptococcaceae (OR = 1.08, 95% CI: 1.01-1.17, p = 0.034), and Peptococcus (OR = 1.05, 95% CI: 1.00-1.10, p = 0.047) were risk factors for SAT production. Meanwhile, Eubacterium fissicatena group (OR = 0.95, 95% CI: 0.91-0.99, p = 0.019), Turicibacter (OR = 0.93, 95% CI: 0.88-0.99, p = 0.022), and Defluviitaleaceae UCG011 (OR = 0.94, 95% CI: 0.89-0.99, p = 0.024) were protective factors for VAT production. Furthermore, Bacteroidetes (OR = 1.09, 95% CI: 1.01-1.17, p = 0.018), Eubacterium eligens group (OR = 1.09, 95% CI: 1.01-1.19, p = 0.037), Alloprevotella (OR = 1.05, 95% CI: 1.00-1.10, p = 0.038), and Phascolarctobacterium (OR = 1.07, 95% CI: 1.00-1.15, p = 0.042) were associated with VAT accumulation. Additionally, reverse MR revealed significant associations between SAT, VAT, and Rikenellaceae RC9 gut group (IVW: OR = 1.57, 95% CI: 1.18-2.09, p = 0.002) as well as Betaproteobacteria (IVW: OR = 1.14, 95% CI: 1.01-1.29, p = 0.029), both acting as risk factors. Sensitivity analyzes during bidirectional MR did not identify heterogeneity or pleiotropy. This study unveils complex causal relationships between gut microbiota and SAT/VAT, providing novel insights into the diagnostic and therapeutic potential of gut microbiota in obesity and related metabolic disorders.

Causal effects of gut microbiota on scoliosis: A bidirectional two-sample mendelian randomization study

BackgroundRecent studies have shown altered gut microbiome composition in patients with scoliosis. However, the causal effect of gut microbiota on scoliosis remains unknown. MethodsA 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. ResultsBilophila, Eubacterium (eligens group), Prevotella9, and Ruminococcus2 were discovered to have a protective effect on the risk of scoliosis. Ruminococcaceae UCG009, Catenibacterium, Coprococcus2, Eubacterium (ventriosum group), Lachnospiraceae (FCS020 group), Ruminiclostridium6, and Mollicutes RF9 may increase the occurrence of scoliosis. Heterogeneity (P > 0.05) and pleiotropy (P > 0.05) analysis confirmed the robustness of the MR results. ConclusionOur 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.

Relationship between gut microbiota dysbiosis and immune indicator in children with sepsis

Sepsis is a life-threatening multiple-organ injury caused by disordered host immune response to microbial infection. However, the correlation between gut microbiota dysbiosis and immune indicators remains unexplored. To address this gap in knowledge, we carried out 16 S rDNA sequencing, analyzed clinical fecal samples from children with sepsis (n = 30) and control children (n = 25), and obtained immune indicators, including T cell subtypes (CD3+, CD3+CD4+, CD3+CD8+, and CD4/CD8), NK cells, cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ), and immunoglobulin indices (IgA, IgE, IgM and IgG). In addition, we analyzed the correlation between gut microbiota dysbiosis and immune indicators, and evaluated the clinical discriminatory power of discovered bacterial biomarkers. We found that children with sepsis exhibited gut bacterial dysbiosis and low alpha diversity. The Spearman’s rank correlation coefficient suggested that Rhodococcus erythropolis had a significantly positive correlation with IFN-γ and CD3+ T cells. Klebsiella pneumoniae and Streptococcus mitis were significantly correlated with NK cells. Bacteroides uniformis was significantly positively correlated with IgM and erythrocyte sedimentation rate, and Eubacterium eligens was significantly positively correlated with IL-4 and CD3+CD8+ T cells. The biomarkers discovered in this study had strong discriminatory power. These changes in the gut microbiome may be closely related to immunologic dysfunction and to the development or exacerbation of sepsis. However, a large sample size is required for verification.

Microbiome and metabolome dysbiosis analysis in impaired glucose tolerance for the prediction of progression to diabetes mellitus

Gut microbiota and circulating metabolite dysbiosis predate important pathological changes in glucose metabolic disorders; however, comprehensive studies on impaired glucose tolerance (IGT), a diabetes mellitus (DM) precursor, are lacking. Here, we perform metagenomic sequencing and metabolomics on 47 pairs of individuals with IGT and newly diagnosed DM and 46 controls with normal glucose tolerance (NGT); patients with IGT are followed up after 4 years for progression to DM. Analysis of baseline data reveals significant differences in gut microbiota and serum metabolites among the IGT, DM, and NGT groups. In addition, 13 types of gut microbiota and 17 types of circulating metabolites showed significant differences at baseline before IGT progressed to DM, including higher levels of Eggerthella unclassified, Coprobacillus unclassified, Clostridium ramosum, L-valine, L-norleucine, and L-isoleucine, and lower levels of Eubacterium eligens, Bacteroides faecis, Lachnospiraceae bacterium 3_1_46FAA, Alistipes senegalensis, Megaspaera elsdenii, Clostridium perfringens, α-linolenic acid, 10E,12Z-octadecadienoic acid, and dodecanoic acid. A random forest model based on differential intestinal microbiota and circulating metabolites can predict the progression from IGT to DM (AUC = 0.87). These results suggest that microbiome and metabolome dysbiosis occur in individuals with IGT and have important predictive values and potential for intervention in preventing IGT from progressing to DM.

Gut microbiota and type 1 diabetes: a two-sample bidirectional Mendelian randomization study.

The real causal relationship between human gut microbiota and T1D remains unclear and difficult to establish. Herein, we adopted a two-sample bidirectional mendelian randomization (MR) study to evaluate the causality between gut microbiota and T1D. We leveraged publicly available genome-wide association study (GWAS) summary data to perform MR analysis. The gut microbiota-related GWAS data from 18,340 individuals from the international consortium MiBioGen were used. The summary statistic data for T1D (n = 264,137) were obtained from the latest release from the FinnGen consortium as the outcome of interest. The selection of instrumental variables conformed strictly to a series of preset inclusion and exclusion criteria. MR-Egger, weighted median, inverse variance weighted (IVW), and weighted mode methods were used to assess the causal association. The Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis were conducted to identify heterogeneity and pleiotropy. At the phylum level, only Bacteroidetes was indicated to have causality on T1D (OR = 1.24, 95% CI = 1.01-1.53, P = 0.044) in the IVW analysis. When it comes to their subcategories, Bacteroidia class (OR = 1.28, 95% CI = 1.06-1.53, P = 0.009, P FDR = 0.085), Bacteroidales order (OR = 1.28, 95% CI = 1.06-1.53, P = 0.009, P FDR = 0.085), and Eubacterium eligens group genus (OR = 0.64, 95% CI = 0.50-0.81, P = 2.84×10-4, P FDR = 0.031) were observed to have a causal relationship with T1D in the IVW analysis. No heterogeneity and pleiotropy were detected. The present study reports that Bacteroidetes phylum, Bacteroidia class, and Bacteroidales order causally increase T1D risk, whereas Eubacterium eligens group genus, which belongs to the Firmicutes phylum, causally decreases T1D risk. Nevertheless, future studies are warranted to dissect the underlying mechanisms of specific bacterial taxa's role in the pathophysiology of T1D.

Causal effects of gut microbiota on the risk of chronic kidney disease: a Mendelian randomization study.

Previous studies have reported that gut microbiota is associated with an increased risk of chronic kidney disease (CKD) progression. However, whether gut microbiota has a causal effect on the development of CKD has not been revealed. Thus, we aimed to analyze the potential causal effect of gut microbiota on the risk of CKD using mendelian randomization (MR) study. Independent single nucleotide polymorphisms closely associated with 196 gut bacterial taxa (N = 18340) were identified as instrumental variables. Two-sample MR was performed to evaluate the causal effect of gut microbiota on CKD (N = 480698), including inverse-variance-weighted (IVW) method, weighted median method, MR-Egger, mode-based estimation and MR-PRESSO. The robustness of the estimation was tested by a series of sensitivity analyses including Cochran's Q test, MR-Egger intercept analysis, leave-one-out analysis and funnel plot. Statistical powers were also calculated. The genetically predicted higher abundance of order Desulfovibrionales was causally associated with an increased risk of CKD (odds ratio = 1.15, 95% confidence interval: 1.05-1.26; p = 0.0026). Besides, we also detected potential causalities between nine other taxa (Eubacterium eligens group, Desulfovibrionaceae, Ruminococcaceae UCG-002, Deltaproteobacteria, Lachnospiraceae UCG-010, Senegalimassilia, Peptostreptococcaceae, Alcaligenaceae and Ruminococcus torques group) and CKD (p < 0.05). No heterogeneity or pleiotropy was detected for significant estimates. We found that Desulfovibrionales and nine other taxa are associated with CKD, thus confirming that gut microbiota plays an important role in the pathogenesis of CKD. Our work also provides new potential indicators and targets for screening and prevention of CKD.

Effects of OsomeFood Clean Label plant-based meals on the gut microbiome

BackgroundPlant-based diets offer more beneficial microbes and can modulate gut microbiomes to improve human health. We evaluated the effects of the plant-based OsomeFood Clean Label meal range (‘AWE’ diet), on the human gut microbiome.MethodsOver 21 days, ten healthy participants consumed OsomeFood meals for five consecutive weekday lunches and dinners and resumed their regular diets for other days/meals. On follow-up days, participants completed questionnaires to record satiety, energy and health, and provided stool samples. To document microbiome variations and identify associations, species and functional pathway annotations were analyzed by shotgun sequencing. Shannon diversity and regular diet calorie intake subsets were also assessed.ResultsOverweight participants gained more species and functional pathway diversity than normal BMI participants. Nineteen disease-associated species were suppressed in moderate-responders without gaining diversity, and in strong-responders with diversity gains along with health-associated species. All participants reported improved short-chain fatty acids production, insulin and γ-aminobutyric acid signaling. Moreover, fullness correlated positively with Bacteroides eggerthii; energetic status with B. uniformis, B. longum, Phascolarctobacterium succinatutens, and Eubacterium eligens; healthy status with Faecalibacterium prausnitzii, Prevotella CAG 5226, Roseburia hominis, and Roseburia sp. CAG 182; and overall response with E. eligens and Corprococcus eutactus. Fiber consumption was negatively associated with pathogenic species.ConclusionAlthough the AWE diet was consumed for only five days a week, all participants, especially overweight ones, experienced improved fullness, health status, energy and overall responses. The AWE diet benefits all individuals, especially those of higher BMI or low-fiber consumption.

Prebiotic potential of apple pomace and pectins from different apple varieties: Modulatory effects on key target commensal microbial populations

Pectin is a group of structurally diverse dietary fibers, very abundant in agri-food waste and by-products such as those generated during apple cider manufacturing. In recent years, pectin and pectinoligosaccharides have demonstrated good fermentation properties and prominent health promoting traits, particularly ameliorating certain inflammatory conditions. In previous investigations apple pomace derived from production of monovarietal Asturian ciders was demonstrated to represent a source of pectin with varied structural characteristics. In this work we investigated in vitro the modulatory effect of pectin and pomace fractions derived from the production of selected monovarietal ciders on human microbiota from healthy subjects and inflammatory bowel disease (IBD) patients through fecal batch fermentations and 16S rRNA gene sequencing. Overall, these fractions promoted the growth of Akkermansia, Lachnospiraceae UCG-010, Prevotella, Sucinivibrio and Turicibacter on samples from healthy donors, while Blautia, Lachnospiraceae CAG-56, Dialister, Eubacterium eligens and Intestinimonas were stimulated in fermentations from IBD patients. The growth of Akkermansia, Blautia, E. eligens group, Intestinimonas and Succinivibrio only occurred with pomace and pectin derived from the tested by-products, and not with other non-pectic prebiotics/substrates. Galactose content and (Arabinose + Galactose)/Rhamnose ratio in apple pomace, and galactose and rhamnose content in pectin, were positively associated to the promotion of most of these genera. This work comprehensively characterize the gut microbiota modulation of apple pectin and pomace fractions derived from cider by-products, demonstrating diverse modulatory capacity of structurally distinct pectin and apple pomace fractions. This diversifies the opportunities to achieve cider by-products valorization through formulation of novel prebiotics for particular population groups.

Relationships between dietary diversity and gut microbial diversity in the elderly.

Diet is considered as a major driver of gut microbiota composition. However, little is known about the relationship between overall dietary balance and gut microbiota, especially in the elderly. Here, using the Quantitative Index for Dietary Diversity (QUANTIDD), we analysed the relationships between dietary diversity and gut microbiota diversity in 445 Japanese subjects aged 65-90 years. We also examined the effect of age by comparing the young-old group aged 65 to 74 years (<75 years group; n=246) and the old-old group aged 75 years and older (≥75 years group; n=199). QUANTIDD showed significant positive relationships with Pielou's evenness and Shannon indices, two α-diversity indices related to the uniformity of species distribution. This suggests that a more diverse diet is associated with a more uniform abundance of various bacterial groups, rather than a greater variety of gut bacteria. QUANTIDD also showed significant positive associations with the abundance of Anaerostipes, Eubacterium eligens group, and Eubacterium ventriosum group, which produce short-chain fatty acids (SCFAs) and are beneficial to health. Negative association was found with the abundance of Ruminococcus gnavus group, which produces inflammatory polysaccharides. Positive associations between QUANTIDD and α-diversity indices or the abundance of specific bacterial groups were identified among all subjects and in the <75 years group, but not in the ≥75 years group. Our results suggest that dietary diversity contributes to the diversity of the gut microbiota and increases the abundance of SCFAs-producing bacteria, but only up to a certain age. These findings help to understand the complex relationship between diet and gut microbiota, and provide hints for specific dietary interventions to promote beneficial gut microbiota in the elderly.