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Frontiers in Microbiology 2024Increasing evidence has suggested that alterations in the gut microbiome are correlated with autoimmune neurologic disorders, yet the causal relationship between them...
BACKGROUND
Increasing evidence has suggested that alterations in the gut microbiome are correlated with autoimmune neurologic disorders, yet the causal relationship between them has yet to be established.
METHODS
From the published genome-wide association study (GWAS) summary statistics, we obtained data on the gut microbiota and three autoimmune neurologic disorders (Multiple Sclerosis, Guillain-Barré Syndrome, and Myasthenia Gravis). We then implemented a two-sample Mendelian Randomization (MR) to determine the causal relationship between the gut microbiota and the diseases. To validate the results, we conducted a series of sensitivity analyses. Finally, to verify the direction of causality, a reverse-causality analysis was done.
RESULTS
We discovered that a higher relative abundance of the genus (OR: 1.213, 95% CI: 1.006-1.462, = 0.043, P = 0.048) and the genus (OR: 1.255, 95% CI: 1.012-1.556, = 0.038, P = 0.048) were associated with a higher risk of MS. Furthermore, the higher the abundance of the class (OR: 3.016, 95% CI: 1.228-7.411, = 0.016, P = 0.021), the genus (OR: 2.787, 95% CI: 1.140-6.816, = 0.025, P = 0.025), and the phylum (OR: 3.016, 95% CI: 1.228-7.411, = 0.016, P = 0.021) was linked to a greater probability of GBS. Additionally, the higher the abundance of the genus (OR: 2.450, 95% CI: 1.072-5.598, = 0.034, P = 0.036), the genus (OR: 2.437, 95% CI: 1.215-4.888, = 0.012, P = 0.024), genus (OR: 3.681, 95% CI: 1.288-10.521, = 0.015, P = 0.025) and the genus (OR: 2.157, 95% CI: 1.211-3.843, = 0.003, P = 0.016) correlated with a greater chance of MG occurrence. No SNPs were identified as outliers through sensitivity analysis. Then, the results of the reverse MR analysis did not indicate any reverse causality.
CONCLUSION
Our findings demonstrate a causal relationship between the gut microbiota and three autoimmune neurologic disorders, providing novel insights into the mechanisms of these autoimmune neurologic disorders that are mediated by gut microbiota.
PubMed: 38721606
DOI: 10.3389/fmicb.2024.1337632 -
Frontiers in Microbiology 2024The dysbiosis of gut microbiota (GM) is considered a contributing factor to prostatitis, yet the causality remains incompletely understood.
BACKGROUND
The dysbiosis of gut microbiota (GM) is considered a contributing factor to prostatitis, yet the causality remains incompletely understood.
METHODS
The genome-wide association study (GWAS) data for GM and prostatitis were sourced from MiBioGen and FinnGen R10, respectively. In the two-sample Mendelian randomization (MR) analysis, inverse variance weighting (IVW), MR-Egger, weighted median, simple mode, weighted mode, and maximum likelihood (ML) methods were utilized to investigate the causal relationship between GM and prostatitis. A series of sensitivity analysis were conducted to confirm the robustness of the main results obtained from the MR analysis.
RESULTS
According to the IVW results, genus (OR: 1.37, 95% CI: 1.09-1.71, = 0.006) and genus (OR: 1.21, 95% CI: 1.02-1.43, = 0.028) were associated with an increased risk of prostatitis. The phylum Verrucomicrobia (OR: 0.76, 95% CI: 0.58-0.98, = 0.033) and genus (OR: 0.84, 95% CI: 0.70-1.00, = 0.045) exhibited a negative association with prostatitis, indicating a potential protective effect. Sensitivity analysis showed that these results were not affected by heterogeneity and horizontal pleiotropy. Furthermore, the majority of statistical methods yielded results consistent with those of the IVW analysis.
CONCLUSIONS
In this study, we identified two GM taxon that might be protective against prostatitis and two GM taxon that could increase the risk of developing prostatitis. These findings could potentially provide a valuable theoretical basis for the future development of preventive and therapeutic strategies for prostatitis.
PubMed: 38680919
DOI: 10.3389/fmicb.2024.1389715 -
Proteomes Apr 2024Millions of people worldwide currently suffer from chronic kidney disease (CKD), requiring kidney replacement therapy at the end stage. Endeavors to better understand...
Millions of people worldwide currently suffer from chronic kidney disease (CKD), requiring kidney replacement therapy at the end stage. Endeavors to better understand CKD pathophysiology from an omics perspective have revealed major molecular players in several sample sources. Focusing on non-invasive sources, gut microbial communities appear to be disturbed in CKD, while numerous human urinary peptides are also dysregulated. Nevertheless, studies often focus on isolated omics techniques, thus potentially missing the complementary pathophysiological information that multidisciplinary approaches could provide. To this end, human urinary peptidome was analyzed and integrated with clinical and fecal microbiome (16S sequencing) data collected from 110 Non-CKD or CKD individuals (Early, Moderate, or Advanced CKD stage) that were not undergoing dialysis. Participants were visualized in a three-dimensional space using different combinations of clinical and molecular data. The most impactful clinical variables to discriminate patient groups in the reduced dataspace were, among others, serum urea, haemoglobin, total blood protein, urinary albumin, urinary erythrocytes, blood pressure, cholesterol measures, body mass index, Bristol stool score, and smoking; relevant variables were also microbial taxa, including a, , , , , , , and ; urinary peptidome fragments were predominantly derived from proteins of collagen origin; among the non-collagen parental proteins were FXYD2, MGP, FGA, APOA1, and CD99. The urinary peptidome appeared to capture substantial variation in the CKD context. Integrating clinical and molecular data contributed to an improved cohort separation compared to clinical data alone, indicating, once again, the added value of this combined information in clinical practice.
PubMed: 38651370
DOI: 10.3390/proteomes12020011 -
BMC Pulmonary Medicine Apr 2024Patients with pulmonary arterial hypertension (PAH) exhibit a distinct gut microbiota profile; however, the causal association between gut microbiota, associated...
BACKGROUND
Patients with pulmonary arterial hypertension (PAH) exhibit a distinct gut microbiota profile; however, the causal association between gut microbiota, associated metabolites, and PAH remains elusive. We aimed to investigate this causal association and to explore whether dietary patterns play a role in its regulation.
METHODS
Summary statistics of gut microbiota, associated metabolites, diet, and PAH were obtained from genome-wide association studies. The inverse variance weighted method was primarily used to measure the causal effect, with sensitivity analyses using the weighted median, weighted mode, simple mode, MR pleiotropy residual sum and outlier (MR-PRESSO), and MR-Egger methods. A reverse Mendelian randomisation analysis was also performed.
RESULTS
Alistipes (odds ratio [OR] = 2.269, 95% confidence interval [CI] 1.100-4.679, P = 0.027) and Victivallis (OR = 1.558, 95% CI 1.019-2.380, P = 0.040) were associated with an increased risk of PAH, while Coprobacter (OR = 0.585, 95% CI 0.358-0.956, P = 0.032), Erysipelotrichaceae (UCG003) (OR = 0.494, 95% CI 0.245-0.996, P = 0.049), Lachnospiraceae (UCG008) (OR = 0.596, 95% CI 0.367-0.968, P = 0.036), and Ruminococcaceae (UCG005) (OR = 0.472, 95% CI 0.231-0.962, P = 0.039) protected against PAH. No associations were observed between PAH and gut microbiota-derived metabolites (trimethylamine N-oxide [TMAO] and its precursors betaine, carnitine, and choline), short-chain fatty acids (SCFAs), or diet. Although inverse variance-weighted analysis demonstrated that elevated choline levels were correlated with an increased risk of PAH, the results were not consistent with the sensitivity analysis. Therefore, the association was considered insignificant. Reverse Mendelian randomisation analysis demonstrated that PAH had no causal impact on gut microbiota-derived metabolites but could contribute to increased the levels of Butyricicoccus and Holdemania, while decreasing the levels of Clostridium innocuum, Defluviitaleaceae UCG011, Eisenbergiella, and Ruminiclostridium 5.
CONCLUSIONS
Gut microbiota were discovered suggestive evidence of the impacts of genetically predicted abundancy of certain microbial genera on PAH. Results of our study point that the production of SCFAs or TMAO does not mediate this association, which remains to be explained mechanistically.
Topics: Humans; Pulmonary Arterial Hypertension; Gastrointestinal Microbiome; Genome-Wide Association Study; Mendelian Randomization Analysis; Familial Primary Pulmonary Hypertension; Choline; Methylamines
PubMed: 38632547
DOI: 10.1186/s12890-024-03008-7 -
Scientific Reports Apr 2024Mounting data hints that the gut microbiota's role may be pivotal in understanding the emergence of psoriasis. However, discerning a direct causal link is yet elusive....
Mounting data hints that the gut microbiota's role may be pivotal in understanding the emergence of psoriasis. However, discerning a direct causal link is yet elusive. In this exploration, we adopted a Mendelian randomization (MR) strategy to probe the prospective causal interplay between the gut's microbial landscape and the predisposition to psoriasis. Genetic markers acting as instrumental variables for gut microbiota were extrapolated from a genome-wide association study (GWAS) encompassing 18,340 individuals. A separate GWAS yielded summary data for psoriasis, which covered 337,159 patients and 433,201 control subjects. The primary analysis hinged on inverse variance weighting (IVW). Additional methods like the weighted median approach and MR-Egger regression were employed to validate the integrity of our findings. Intriguing correlations emerged between psoriasis risk and eight specific bacterial traits. To illustrate: Mollicutes presented an odds ratio (OR) of 1.003 with a 95% confidence interval (CI) spanning 1.001-1.005 (p = 0.016), while the family. Victivallaceae revealed an OR of 0.998 with CI values between 0.997 and 0.999 (p = 0.023). Eubacterium (coprostanoligenes group) revealed an OR of 0.997 with CI values between 0.994 and 0.999 (p = 0.027). Eubacterium (fissicatena group) revealed an OR of 0.997 with CI values between 0.996 and 0.999 (p = 0.005). Holdemania revealed an OR of 1.001 with CI values 1-1.003 (p = 0.034). Lachnospiraceae (NK4A136 group) revealed an OR of 0.997 with CI values between 0.995 and 0.999 (p = 0.046). Lactococcus revealed an OR of 0.998 with CI values between 0.996 and 0.999 (p = 0.008). Tenericutes revealed an OR of 1.003 with CI values between 1.001 and 1.006 (p = 0.016). Sensitivity analysis for these bacterial features yielded congruent outcomes, reinforcing statistically significant ties between the eight bacterial entities and psoriasis. This comprehensive probe underscores emerging evidence pointing towards a plausible causal nexus between diverse gut microbiota and the onset of psoriasis. It beckons further research to unravel the intricacies of how the gut's microbial constituents might sway psoriasis's pathogenesis.
Topics: Humans; Gastrointestinal Microbiome; Genome-Wide Association Study; Mendelian Randomization Analysis; Prospective Studies; Tenericutes; Clostridiales; Eubacterium
PubMed: 38632320
DOI: 10.1038/s41598-024-59603-5 -
Scientific Reports Apr 2024Vulvar lichen sclerosus (VLS) is a chronic and progressive dermatologic condition that can cause physical dysfunction, disfigurement, and impaired quality of life....
Vulvar lichen sclerosus (VLS) is a chronic and progressive dermatologic condition that can cause physical dysfunction, disfigurement, and impaired quality of life. However, the etiology of VLS remains unknown. The vulvar skin, intestinal and vaginal microbiomes have been postulated to play important roles in the pathogenesis of this disease. The aim of this study was to compare the compositional characteristics of the vulvar skin, vagina, and gut microbiota between perimenopausal or postmenopausal VLS patients and healthy controls. The study involved six perimenopausal or postmenopausal VLS patients which were based on characteristic clinical manifestations and histologic confirmation and five healthy controls. The pruritus severity of each patient was evaluated using the NRS scale, and the dermatology-specific health-related quality of life was assessed using the Skindex-16. Metagenomic sequencing was performed, and the results were analyzed for alpha and beta diversity. LEfSe analysis were used to investigate the microbial alterations in vulvar skin, gut and vagina. KEGG databases were used to analyze differences in functional abundance. The study found significant differences in alpha diversity between the two groups in stool and vaginal samples (P < 0.05). Patients with VLS had a higher abundance of Enterobacter cloacae, Flavobacterium_branchiophilum, Mediterranea_sp._An20, Parabacteroides_johnsoniiand Streptococcus_bovimastitidis on the vulvar skin, while Corynebacterium_sp._zg-913 was less abundant compared to the control group. The relative abundance of Sphingomonas_sp._SCN_67_18, Sphingobium_sp._Ant17, and Pontibacter_sp_BT213 was significantly higher in the gut samples of patients with VLS.Paenibacillus_popilliae,Gemella_asaccharolytica, and Coriobacteriales_bacterium_DNF00809 compared to the control group. Additionally, the vaginal samples of patients with VLS exhibited a significantly lower relative abundance of Bacteroidales_bacterium_43_8, Bacteroides_sp._CAG:20, Blautia_sp._AM28-10, Fibrobacter_sp._UWB16, Lachnospiraceae_bacterium_AM25-39, Holdemania_filiformis, Lachnospiraceae_bacterium_GAM79, and Tolumonas_sp. Additionally, the butyrate-producing bacterium SS3/4 showed a significant difference compared to the controls. The study found a negative relationship between Sphingobium_sp._Ant17 in stool and Skindex-16 (P < 0.05), while Mediterranea_sp._An20 had a positive correlation with Skindex-16 (P < 0.05) in the skin. Additionally, our functional analysis revealed alterations in Aminoacyl_tRNA_biosynthesis, Glutathione_metabolism, the pentose phosphate pathway, and Alanine__aspartate_and_glutamate_metabolism in the VLS patient group. The study suggests that perimenopausal or postmenopausal patients with VLS have a modified microbiome in the vulvar skin, gut, and vagina. This modification is linked to abnormal energy metabolism, increased oxidative stress, and abnormal amino acid metabolism.
Topics: Female; Humans; Vulvar Lichen Sclerosus; Postmenopause; Perimenopause; Quality of Life; Microbiota; Arrhythmias, Cardiac; Vagina
PubMed: 38600101
DOI: 10.1038/s41598-024-58983-y -
Frontiers in Pharmacology 2024Metabolic syndrome (MetS) is a clinical condition associated with multiple metabolic risk factors leading to type 2 diabetes mellitus and other metabolic diseases....
Metabolic syndrome (MetS) is a clinical condition associated with multiple metabolic risk factors leading to type 2 diabetes mellitus and other metabolic diseases. Recent evidence suggests that modulating adipose tissue to adaptive thermogenesis may offer therapeutic potential for MetS. Xiasangju (XSJ) is a marketed drug and dietary supplement used for the treatment of metabolic disease with anti-inflammatory activity. This study investigated the therapeutic effects of XSJ and the underlying mechanisms affecting the activation of brown adipose tissue (BAT) in MetS. The results revealed that XSJ ameliorated MetS by enhancing glucose and lipid metabolism, leading to reduced body weight and abdominal circumference, decreased adipose tissue and liver index, and improved blood glucose tolerance. XSJ administration stimulated catecholamine biosynthesis, increasing noradrenaline (NA) levels and activating NA-mediated proteins in BAT. Thus, BAT enhanced thermogenesis and oxidative phosphorylation (OXPHOS). Moreover, XSJ induced changes in gut microbiota composition, with an increase in abundance and a decrease in , , , and . XSJ upregulated the proteins associated with intestinal tight junctions corresponding with lower serum lipopolysaccharide (LPS), tumor necrosis factor (TNF-) monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) levels to maintain NA signaling transport. In summary, XSJ may alleviate MetS by promoting thermogenesis in BAT to ultimately boost energy metabolism through increasing NA biosynthesis, strengthening intestinal barrier integrity and reducing low-grade inflammation. These findings suggest XSJ has potential as a natural therapeutic agent for the treatment of MetS.
PubMed: 38576483
DOI: 10.3389/fphar.2024.1371929 -
Frontiers in Nutrition 2024Multiple observational studies suggest a connection between the composition of the gut microbiota and hypothyroidism. However, it has yet to be determined whether the...
BACKGROUND
Multiple observational studies suggest a connection between the composition of the gut microbiota and hypothyroidism. However, it has yet to be determined whether the gut microbiota has a causal effect on hypothyroidism.
METHODS
To investigate the connection between the gut microbiota and hypothyroidism, two-sample Mendelian randomization was performed using data from a genome-wide association study meta-analysis ( = 18,430) conducted by the MiBioGen consortium. Summary statistics for hypothyroidism (26,342 cases and 59,827 controls) were obtained using the data from the FinnGen consortium R8 release data. To investigate the causal link between the gut microbiota and hypothyroidism, various methods, including MR-Egger, weighted median, weighted model, simple model, MR-PRESSO, and inverse variance weighted (IVW), were employed. The bacteria that were causally linked to hypothyroidism in forward Mendelian randomization analysis were subjected to reverse Mendelian randomization analysis. Cochran's statistics were utilized to gauge the heterogeneity of the instrumental variables.
RESULTS
The results indicated that Akkermansia had a positive impact on hypothyroidism, with an odds ratio of 0.84 (95% CI 0.74-0.95, = 0.01) based on the inverse variance-weighted estimates. Additionally, Anaerostipes (OR = 1.17, 95% CI 1.01-1.36, = 0.04), Butyrivibrio (OR = 0.93, 95% CI 0.88-0.99, = 0.02), Holdemania (OR = 0.89, 95% CI 0.81-0.99, = 0.03), Intestinimonas (OR = 1.13, 95% CI 1.02-1.26, = 0.03), Ruminiclostridium5 (OR = 1.19, 95% CI 1.01-1.41, = 0.04), and Ruminococcaceae UCG-011 (OR = 0.91, 95% CI 0.84-0.99, = 0.03) were identified. The gut microbiota was not significantly affected by hypothyroidism, as indicated by the results of the reverse MR analysis. There was no significant variation in the instrumental variables or horizontal pleiotropy.
CONCLUSION
The findings of this study using two-sample Mendelian randomization indicate a causal relationship between Akkermansia and hypothyroidism. Increased Akkermansia inhibits the onset and progression of hypothyroidism. Additional randomized controlled experiments are necessary to elucidate the beneficial impact of probiotics on hypothyroidism and their distinct protective mechanisms.
PubMed: 38562485
DOI: 10.3389/fnut.2024.1286593 -
International Journal of Molecular... Mar 2024The integrated dysbiosis of gut microbiota and altered host transcriptomics in irritable bowel syndrome (IBS) is yet to be known. This study investigated the...
The integrated dysbiosis of gut microbiota and altered host transcriptomics in irritable bowel syndrome (IBS) is yet to be known. This study investigated the associations among gut microbiota and host transcriptomics in young adults with IBS. Stool and peripheral blood samples from 20 IBS subjects and 21 healthy controls (HCs) collected at the baseline visit of an RCT were sequenced to depict the gut microbiota and transcriptomic profiles, respectively. The diversities, composition, and predicted metabolic pathways of gut microbiota significantly differed between IBS subjects and HCs. Nine genera were significantly abundant in IBS stool samples, including , , , , , , , , and . There were 2264 DEGs found between IBS subjects and HCs; 768 were upregulated, and 1496 were downregulated in IBS participants compared with HCs. The enriched gene ontology included the immune system process and immune response. The pathway of antigen processing and presentation (hsa04612) in gut microbiota was also significantly different in the RNA-seq data. , , , and were significantly correlated with (upregulated, positive correlations), (downregulated, negative correlations), and (downregulated, negative correlations). This study identified the dysregulated immune response and metabolism in IBS participants revealed by the altered gut microbiota and transcriptomic profiles.
Topics: Humans; Young Adult; Irritable Bowel Syndrome; Multiomics; Gastrointestinal Microbiome; Feces; Firmicutes; Immunity; Gene Expression Profiling
PubMed: 38542485
DOI: 10.3390/ijms25063514 -
Medicine Mar 2024Endometriosis is a prevalent condition with notable impacts on fertility. Recent studies have implicated gut microbiota in the development of endometriosis associated...
Endometriosis is a prevalent condition with notable impacts on fertility. Recent studies have implicated gut microbiota in the development of endometriosis associated infertility (EAI). This study employs Mendelian randomization (MR) to elucidate the causal relationship between specific gut microbes and EAI. Using MR, we selected single nucleotide polymorphisms associated with 211 gut microbiota taxa from large-scale genome-wide association studies summary data. We applied statistical methods including inverse variance weighting, weighted median, and MR-Egger for analysis. Outliers were identified through the leave-one-out method. MR-Egger intercept tests were conducted to address horizontal pleiotropy, while Cochran Q and P values assessed heterogeneity. The false discovery rate method was used for multiple testing correction. Sensitivity analysis and F statistics evaluated the reliability and potential biases of our results. The inverse variance weighting method indicated a significant association of the genus Actinomyces (OR = 1.657, 95% CI: 1.187-2.312, P = .00298) with an increased risk of EAI. Conversely, genera Holdemania (OR = 0.630, 95% CI: 0.444-0.894, P = .00969) and Ruminococcaceae NK4A214 group (OR = 0.689, 95% CI: 0.481-0.999, P = .0439) appeared as protective factors. MR-PRESSO global test and MR-Egger regression indicated no significant horizontal pleiotropy (P > .05). Leave-one-out analysis confirmed the robustness of these findings. Our study provides evidence of a causal relationship between specific gut microbiome taxa and EAI. These findings offer novel insights and may guide the development of new preventive and therapeutic strategies for managing EAI.
Topics: Female; Humans; Gastrointestinal Microbiome; Endometriosis; Genome-Wide Association Study; Mendelian Randomization Analysis; Reproducibility of Results; Infertility
PubMed: 38518021
DOI: 10.1097/MD.0000000000037383