-
Frontiers in Endocrinology 2023There is some evidence for an association between gut microbiota and nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), and viral hepatitis, but no...
OBJECTIVE
There is some evidence for an association between gut microbiota and nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), and viral hepatitis, but no studies have explored their causal relationship.
METHODS
Instrumental variables of the gut microbiota (N = 13266) and gut microbiota-derived metabolites (N = 7824) were acquired, and a Mendelian randomization study was performed to explore their influence on NAFLD (1483 European cases and 17,781 European controls), ALD (2513 European cases and 332,951 European controls), and viral hepatitis risk (1971 European cases and 340,528 European controls). The main method for examining causality is inverse variance weighting (IVW).
RESULTS
IVW results confirmed that ( = 0.0249), ( = 0.0237), ( = 0.0245), ( = 0.0083), ( = 0.0163), and ( = 0.0472) were protective factors for NAFLD, and ( = 0.0120) was detrimental for NAFLD. The higher abundance of three genera, ( = 0.0388), ( = 0.0252), and ( = 0.0364), was correlated with a lower risk of ALD, while level was associated with a higher risk of ALD ( = 0.0371). The ( = 0.0069) and ( = 0.0195) were related to a higher risk of viral hepatitis. Besides, alanine ( = 0.0076) and phenyllactate ( = 0.0100) were found to be negatively correlated with NAFLD, while stachydrine (O = 0.0244) was found to be positively associated with NAFLD. The phenylacetate ( = 0.0353) and ursodeoxycholate ( = 0.0144) had a protective effect on ALD, while the threonate ( = 0.0370) exerted a detrimental influence on ALD. The IVW estimates of alanine ( = 0.0408) and cholate ( = 0.0293) showed their suggestive harmful effects against viral hepatitis, while threonate ( = 0.0401) displayed its suggestive protective effect against viral hepatitis.
CONCLUSION
In conclusion, our research supported causal links between the gut microbiome and its metabolites and NAFLD, ALD, and viral hepatitis.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Gastrointestinal Microbiome; Mendelian Randomization Analysis; Alanine; Clostridiales
PubMed: 37476494
DOI: 10.3389/fendo.2023.1159148 -
Journal of Cancer 2024Regulating the immune system is a crucial measure of gut microbiota (GM) that influences the development of diseases. The causal role of GM on Non-small cell lung...
Regulating the immune system is a crucial measure of gut microbiota (GM) that influences the development of diseases. The causal role of GM on Non-small cell lung cancer (NSCLC) and whether it can be mediated by immune cells is still unknown. We performed a two-step, two-sample Mendelian randomization study with an Inverse variance weighted (IVW) approach to investigate the causal role of GM on NSCLC and the mediation effect of immune cells between the association of GM and NSCLC. MR analyses determined the protective effects of 6 genera on NSCLC (Bacteroides, Roseburia, Alistipes, Methanobrevibacter, Ruminococcus gauvreauii group, and Peptococcus). In addition, 38 immune cell traits were suggestively associated with NSCLC. Of note, the mediation MR illustrated the causal role of Genus-Peptococcus on NSCLC (Total effect IVW: OR = 0.790, 95% CI [0.657, 0.950], P = 0.012) was to a large proportion mediated by CD45 on HLA DR CD4 in TBNK panel (-034 (95% CI [-0.070, -0.005]; P = 0.037), accounting for 14.4% of Total effect). The study suggested a causal relationship between GM and NSCLC, which may be mediated by immune cells.
PubMed: 38434967
DOI: 10.7150/jca.92699 -
Causal effect of gut microbiota on Gastroduodenal ulcer: a two-sample Mendelian randomization study.Frontiers in Cellular and Infection... 2023Gastroduodenal ulcers are associated with infection and the use of nonsteroidal anti-inflammatory drugs (NSAIDs). However, the causal relationship between...
BACKGROUND
Gastroduodenal ulcers are associated with infection and the use of nonsteroidal anti-inflammatory drugs (NSAIDs). However, the causal relationship between gastroduodenal ulcers and gut microbiota, especially specific gut microbiota, remains unclear.
METHODS
We conducted an analysis of published data on the gut microbiota and Gastroduodenal ulcer using genome-wide association studies (GWAS). Two-sample Mendelian randomization (MR) analysis was performed to determine the causal relationship between gut microbiota and Gastroduodenal ulcer. Sensitivity, heterogeneity, and pleiotropy analyses were conducted to confirm the accuracy of the research findings.
RESULTS
Our study showed that the abundance of , , , , , and was negatively correlated with the risk of Gastroduodenal ulcer. Conversely, the abundance of , , , , , , and was positively correlated with the risk of Gastroduodenal ulcer. MR analysis revealed causal relationships between 13 bacterial genera and Gastroduodenal ulcer.
CONCLUSION
This study represents a groundbreaking endeavor by furnishing preliminary evidence regarding the potentially advantageous or detrimental causal link between the gut microbiota and Gastroduodenal ulcer, employing Mendelian Randomization (MR) analysis for the first time. These discoveries have the potential to yield fresh perspectives on the prevention and therapeutic approaches concerning Gastroduodenal ulcer, with a specific focus on the modulation of the gut microbiota.
Topics: Humans; Gastrointestinal Microbiome; Genome-Wide Association Study; Helicobacter Infections; Mendelian Randomization Analysis; Helicobacter pylori; Peptic Ulcer; Clostridiaceae; Clostridiales
PubMed: 38156322
DOI: 10.3389/fcimb.2023.1322537 -
European Journal of Medical Research Sep 2023Inflammatory disorders of the breast (IDB) damages the interests of women and children and hinders the progress of global health seriously. Several studies had offered...
BACKGROUND
Inflammatory disorders of the breast (IDB) damages the interests of women and children and hinders the progress of global health seriously. Several studies had offered clues between gut microbiota (GM) and inflammatory disorders of the breast (IDB). The gut-mammary gland axis also implied a possible contribution of the GM to IDB. However, the causality between them is still elusive.
METHODS
The data of two-sample Mendelian randomization (MR) study related to the composition of GM (n = 18,340) and IDB (n = 177,446) were accessed from openly available genome-wide association studies (GWAS) database. As the major analytical method, inverse variance weighted (IVW) was introduced and several sensitive analytical methods were conducted to verify results.
RESULTS
Inverse variance weighted revealed Eubacterium rectale group (OR = 1.87, 95% CI: 1.02-3.43, p = 4.20E-02), Olsenella (OR = 1.29, 95% CI: 1.02-1.64, p = 3.30E-02), Ruminiclostridium-6 (OR = 1.53, 95% CI: 1.08-2.14, p = 1.60E-02) had an anti-protective effect on IDB. Peptococcus (OR = 0.75, 95% CI: 0.60-0.94, p = 1.30E-02) had a protective effect on IDB. The results were credible through a series of test.
CONCLUSIONS
We revealed causality between IDB and GM taxa, exactly including Ruminiclostridium-6, Eubacterium rectale group, Olsenella and Peptococcus. These genera may become novel biomarkers and supply new viewpoint for probiotic treatment. However, these findings warrant further test owing to the insufficient evidences.
Topics: Child; Female; Humans; Gastrointestinal Microbiome; Genome-Wide Association Study; Actinobacteria; Evidence Gaps; Probiotics
PubMed: 37679821
DOI: 10.1186/s40001-023-01281-6 -
Frontiers in Microbiology 2024The link between Gut microbiota (GM) and Gallstone disease (GSD) is well established, but it is not clear whether there is a causal relationship between the two...
BACKGROUND
The link between Gut microbiota (GM) and Gallstone disease (GSD) is well established, but it is not clear whether there is a causal relationship between the two associations.
METHODS
We conducted bidirectional Mendelian randomization (MR) analyses, leveraging aggregated data from the Genome-Wide Association Study (GWAS) of GM and Circulating Metabolites. Our primary objective was to investigate the causal interplay between intestinal flora and GSD. Additionally, we performed mediational analyses, two-step MR, and multivariate MR to uncover the potential mediating effect of circulating metabolites in this relationship.
RESULT
Our study has revealed a causal relationship between GSD and six distinct bacterial groups. Genetically predicted Class Bacilli (Odds Ratio (OR): 0.901, 95% Confidence Interval (95% CI): 0.825-0.985; 0.021), Order Lactobacillales (OR: 0.895, 95% CI: 0.816-0.981; 0.017), and Genus Coprococcus 2 (OR: 0.884, 95% CI: 0.804-0.973; 0.011) were inversely associated with the risk of GSD. Conversely, the Genus Clostridiumsensustricto1 (OR: 1.158, 95% CI: 1.029-1.303; = 0.015), Genus Coprococcus3 (OR: 1.166, 95% CI: 1.024-1.327; = 0.020), and Genus Peptococcus (OR: 1.070, 95% CI: 1.017-1.125; 0.009) were positively associated with the risk of GSD. Moreover, our findings suggest that the positive influence of the Genus Peptococcus on GSD may be mediated through Omega-3 polyunsaturated fatty acids (PUFA).
CONCLUSION
This study reinforces the connection between the gut microbiome and the risk of GSD while also unveiling the mediating role of Omega-3 PUFA in the causal relationship between these factors.
PubMed: 38333586
DOI: 10.3389/fmicb.2024.1336673 -
Frontiers in Microbiology 2023Numerous studies have revealed associations between gut microbiota and adipose tissue. However, the specific functional bacterial taxa and their causal relationships...
BACKGROUND
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.
METHODS
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.
RESULTS
IVW results demonstrated that were protective factors for SAT production (OR = 0.88, 95% CI: 0.80-0.96, = 0.005) and VAT production (OR = 0.91, 95% CI: 0.83-0.99, = 0.030). Various bacterial taxa including (OR = 0.94, 95% CI: 0.89-0.99, = 0.017), (OR = 0.96, 95% CI: 0.92-1.00, = 0.029), and (OR = 0.90, 95% CI: 0.83-0.98, = 0.012) were associated only with decreased SAT production. (OR = 1.05, 95% CI: 1.02-1.10, = 0.005), (OR = 1.08, 95% CI: 1.01-1.15, = 0.028), (OR = 1.08, 95% CI: 1.01-1.17, = 0.034), and (OR = 1.05, 95% CI: 1.00-1.10, = 0.047) were risk factors for SAT production. Meanwhile, (OR = 0.95, 95% CI: 0.91-0.99, = 0.019), (OR = 0.93, 95% CI: 0.88-0.99, = 0.022), and Defluviitaleaceae UCG011 (OR = 0.94, 95% CI: 0.89-0.99, = 0.024) were protective factors for VAT production. Furthermore, (OR = 1.09, 95% CI: 1.01-1.17, = 0.018), (OR = 1.09, 95% CI: 1.01-1.19, = 0.037), Alloprevotella (OR = 1.05, 95% CI: 1.00-1.10, = 0.038), and (OR = 1.07, 95% CI: 1.00-1.15, = 0.042) were associated with VAT accumulation. Additionally, reverse MR revealed significant associations between SAT, VAT, and (IVW: OR = 1.57, 95% CI: 1.18-2.09, = 0.002) as well as (IVW: OR = 1.14, 95% CI: 1.01-1.29, = 0.029), both acting as risk factors. Sensitivity analyzes during bidirectional MR did not identify heterogeneity or pleiotropy.
CONCLUSION
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.
PubMed: 38029216
DOI: 10.3389/fmicb.2023.1285982 -
Food & Function Oct 2023The protective effects of yak milk (YM) against chronic alcoholic liver injury in rats were investigated in this study. Histologic and biochemical analyses demonstrated...
The protective effects of yak milk (YM) against chronic alcoholic liver injury in rats were investigated in this study. Histologic and biochemical analyses demonstrated that YM consumption ameliorates alcohol-induced liver injury by increasing the liver antioxidant enzyme activity and reducing inflammation. Furthermore, microbiome and metabolomic analyses exploring YM's impact on gut microbiota and metabolism found that YM administration regulates gut microbiota composition. Specifically, there was a decrease in the relative abundance of , , and , along with an increase in and . Moreover, Pearson analysis indicated positive correlations between and with ALT and AST levels, while showing a negative correlation with ADH levels. Furthermore, differential metabolite analysis of fecal samples from the YM group identified significant increases in the taurine (2-Aminoethanesulfonic acid), hypotaurine (2-Aminoethanesulfonic Acid) and isethionic acid levels. Finally, KEGG topology analysis highlighted taurine and hypotaurine metabolism as the primary pathways influenced by YM intervention. Therefore, these findings collectively suggest that YM may protect alcohol-exposed rats against liver injury by modulating oxidative stress, inflammatory response, gut microbiota disorder, and metabolic regulation.
Topics: Rats; Cattle; Animals; Milk; Chemical and Drug Induced Liver Injury, Chronic; Liver; Ethanol; Taurine; Antioxidants
PubMed: 37853817
DOI: 10.1039/d3fo03675h -
Progress in Neuro-psychopharmacology &... Dec 2023Previous studies have reported a variety of gut microbiota alterations in patients with schizophrenia. However, none of these studies has investigated gut microbiota in...
BACKGROUND
Previous studies have reported a variety of gut microbiota alterations in patients with schizophrenia. However, none of these studies has investigated gut microbiota in patients with the deficit subtype of schizophrenia (D-SCZ) that can be characterized by primary and enduring negative symptoms. Therefore, in this study we aimed to profile gut microbiota of individuals with D-SCZ, compared to those with non-deficit schizophrenia (ND-SCZ) and healthy controls (HCs).
METHODS
A total of 115 outpatients (44 individuals with D-SCZ and 71 individuals with ND-SCZ) during remission of positive and disorganization symptoms as well as 120 HCs were enrolled. Gut microbiota was analyzed using the 16 rRNA amplicon sequencing. Additionally, the levels of C-reactive protein (CRP), glucose and lipid metabolism markers were determined in the peripheral blood samples.
RESULTS
Altogether 14 genera showed differential abundance in patients with D-SCZ compared to ND-SCZ and HCs, including Candidatus Soleaferrea, Eubacterium, Fusobacterium, Lachnospiraceae UCG-002, Lachnospiraceae UCG-004, Lachnospiraceae UCG-010, Libanicoccus, Limosilactobacillus, Mogibacterium, Peptococcus, Prevotella, Prevotellaceae NK3B31 group, Rikenellaceae RC9 gut group, and Slackia after adjustment for potential confounding factors. Observed alterations were significantly associated with cognitive performance in both groups of patients. Moreover, several significant correlations of differentially abundant genera with the levels of CRP, lipid profile parameters, glucose and insulin were found across all subgroups of participants.
CONCLUSION
Findings from the present study indicate that individuals with D-SCZ show a distinct profile of gut microbiota alterations that is associated with cognitive performance, metabolic parameters and subclinical inflammation.
Topics: Humans; Gastrointestinal Microbiome; Schizophrenia; Case-Control Studies; Glucose; Clostridiales
PubMed: 37473955
DOI: 10.1016/j.pnpbp.2023.110834 -
ACS Chemical Neuroscience Mar 2024Alteration of gut microbiota and microbial metabolites such as short-chain fatty acids (SCFAs) coexisted with stress-generated brain disorders, including depression....
Alteration of gut microbiota and microbial metabolites such as short-chain fatty acids (SCFAs) coexisted with stress-generated brain disorders, including depression. Herein, we investigated the effect of SCFAs in a treatment-resistant depression (TRD) model of rat. Rats were exposed to chronic-unpredictable mild stress (CUMS) and repeated adrenocorticotropic hormone (ACTH) injections to generate a TRD-like phenotype. The cecal contents of these animals were engrafted into healthy-recipient rats and allowed to colonize for 4 weeks (TRD-FMT group). Blood, brain, colon, fecal, and cecal samples were collected for molecular studies. Rats exposed to CUMS + ACTH showed TRD-like phenotypes in sucrose-preference (SPT), forced swim (FST), and elevated plus maze (EPM) tests. The TRD-FMT group also exhibited anxiety- and depression-like behaviors. Administration of SCFAs (acetate, propionate, and butyrate at 67.5, 25, and 40 mM, respectively) for 7 days exerted robust antidepressant and antianxiety effects by restoring the levels of SCFAs in plasma and fecal samples, and proinflammatory cytokines (TNF-α and IL-6), serotonin, GABA, norepinephrine, and dopamine in the hippocampus and/or frontal cortex of TRD and TRD-FMT animals. SCFAs treatment elevated the expression of free-fatty acid receptors 2/3, BDNF, doublecortin, and zonula-occludens, and reduced the elevated plasma levels of kynurenine and quinolinic acid and increased mucus-producing goblet cells in TRD and TRD-FMT animals. In 16S sequencing results, decreased microbial diversity in TRD rats corresponds with differences in the genus of , , , , , , _UCG-014, _UCG-002, , , and . SCFAs may impart beneficial effects via modulation of tryptophan metabolism, inflammation, neurotransmitters, and microbiota-gut-brain axis in TRD rats.
Topics: Rats; Animals; Depression; Anxiety; Fatty Acids, Volatile; Phenotype; Adrenocorticotropic Hormone; Dietary Supplements; Stress, Psychological
PubMed: 38382546
DOI: 10.1021/acschemneuro.3c00727 -
Causal effects between gut microbiota and endometriosis: a two-sample Mendelian randomisation study.Journal of Obstetrics and Gynaecology :... Dec 2024Previous observational evidence has indicated the potential involvement of the gut microbiota (GM) in the development of endometriosis. However, the causal relationship...
BACKGROUND
Previous observational evidence has indicated the potential involvement of the gut microbiota (GM) in the development of endometriosis. However, the causal relationship of the association remains to be investigated.
METHOD
Genome-wide association study (GWAS) data of GM was obtained from the MiBioGen consortium, and GWAS for endometriosis data was from the FinnGen consortium. Initially, a two-sample Mendelian randomisation (MR) analysis was performed to identify specific bacteria associated with endometriosis. Inverse variance-weighted (IVW) was used as the main MR analysis to infer causal relationships. The other four popular MR methods including MR-Egger regression, weighted mode, weighted median, and simple mode were used for secondary confirmation. Subsequently, these selected bacteria were employed as exposure to investigate their causal effects on six sub-types of endometriosis. Furthermore, reverse MR analysis was implemented to evaluate the reverse causal effects. Cochran's Q statistics was used to test the heterogeneity of instrumental variables (IVs); MR-Egger regression was used to test horizontal pleiotropy; MR-PRESSO and leave-one-out sensitivity analysis were applied to find significant outliers.
RESULT
A total of 1131 single nucleotide polymorphisms (SNPs) were collected as IVs for 196 GM taxa with endometriosis as the outcome. We identified 12 causal relationships between endometriosis and GM taxa including 1 phylum, 3 families, 2 orders, and 6 genera (Rikenellaceae RC9 gut group, Eubacterium ruminantium group, Faecalibacterium, Peptococcus, Clostridium sensu stricto 1, and Ruminococcaceae UCG005). Utilizing the Bonferroni method, we identified phylum Cyanobacteria as the strongest associated GM taxa. Subsequently, 6 significant causal effects were uncovered between the 12 selected specific GM and 6 sub-types of endometriosis. Meanwhile, no reverse causal relationship was found. Further, no horizontal pleiotropy and no significant outliers were detected in the sensitive analysis.
CONCLUSIONS
This MR analysis revealed significant causal effects between GM and endometriosis and phylum Cyanobacteria had the strongest association.
Topics: Endometriosis; Humans; Female; Mendelian Randomization Analysis; Genome-Wide Association Study; Gastrointestinal Microbiome; Polymorphism, Single Nucleotide; Causality
PubMed: 38885114
DOI: 10.1080/01443615.2024.2362415