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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 -
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 -
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 -
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 -
Aging Cell Mar 2024The Methionine restriction (MR) diet has been shown to delay aging and extend lifespan in various model organisms. However, the long-term effects of MR diet on the gut...
The Methionine restriction (MR) diet has been shown to delay aging and extend lifespan in various model organisms. However, the long-term effects of MR diet on the gut microbiome composition remain unclear. To study this, male mice were started on MR and control diet regimens at 6 months and continued until 22 months of age. MR mice have reduced body weight, fat mass percentage, and bone mineral density while having increased lean mass percentage. MR mice also have increased insulin sensitivity along with increasing indirect calorimetry markers such as energy expenditure, oxygen consumption, carbon dioxide production, and glucose oxidation. Fecal samples were collected at 1 week, 18 weeks, and 57 weeks after the diet onset for 16S rRNA amplicon sequencing to study the gut microbiome composition. Alpha and beta diversity metrics detected changes occurring due to the timepoint variable, but no changes were detected due to the diet variable. The results from LEfSe analysis surprisingly showed that more bacterial taxa changes were linked to age rather than diet. Interestingly, we found that the long-term MR diet feeding induced smaller changes compared to short-term feeding. Specific taxa changes due to the diet were observed at the 1 or 18-week time points, including Ileibacterium, Odoribacter, Lachnoclostridium, Marinifilaceae, and Lactobacillaceae. Furthermore, there were consistent aging-associated changes across both groups, with an increase in Ileibacterium and Erysipelotrichaceae with age, while Eubacterium_coprostanoligenes_group, Ruminococcaceae, Peptococcaceae, and Peptococcus decreased with age.
Topics: Male; Mice; Animals; Methionine; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Diet; Body Weight; Racemethionine
PubMed: 38279509
DOI: 10.1111/acel.14051 -
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 -
Frontiers in Microbiology 2023Oxidative stress, inflammatory response, and gut-liver axis dysbiosis have been suggested as the primarily involved in the pathogenesis of alcoholic liver injury....
Oxidative stress, inflammatory response, and gut-liver axis dysbiosis have been suggested as the primarily involved in the pathogenesis of alcoholic liver injury. Previous research established that yeast extract (YE) has antioxidant, immune-boosting or microbiota-regulating properties. However, there is currently lack of information regarding the efficacy of YE on alcoholic liver injury. This study seeks to obtain data that will help to address this research gap using a Wistar male rat experimental model. Histologic and biochemical analysis results showed that the groups treated with both low-dose yeast extract (YEL) and high-dose yeast extract (YEH) had lower degrees of alcohol-induced liver injury. The abundance of and reduced in the low-dose yeast extract (YEL) group, while that of , , and reduced in the high-dose (YEH) group. Furthermore, Spearman analysis showed that the gut microbes were significantly associated with several liver-related indicators. For the analysis of differential metabolites and enriched pathways in the YEL group, the abundance of lysophosphatidylcholine (16:0/0:0) significantly increased, and then the levels of histamine, adenosine and 5' -adenine nucleotide were remarkedly elevated in the YEH group. These findings suggest that both high and low doses of YE can have different protective effects on liver injury in alcoholic liver disease (ALD) rats, in addition to improving gut microbiota disorder. Besides, high-dose YE has been found to be more effective than low-dose YE in metabolic regulation, as well as in dealing with oxidative stress and inflammatory responses.
PubMed: 37547679
DOI: 10.3389/fmicb.2023.1217449 -
Frontiers in Microbiology 2024Increasing numbers of people are suffering from sleep disorders. The gut microbiota of these individuals differs significantly. However, no reports are available on the...
BACKGROUND
Increasing numbers of people are suffering from sleep disorders. The gut microbiota of these individuals differs significantly. However, no reports are available on the causal associations between specific gut microbiota and sleep disorders.
METHODS
Data on gut genera were obtained from the MiBioGen consortium. Twenty-four cohorts with 18,340 individuals of European origin were included. Sleep disorder data, which included 216,454 European individuals, were retrieved from the FinnGen Biobank. Subsequently, two-sample Mendelian randomization was performed to analyze associations between sleep disorders and specific components of the gut microbiota.
RESULTS
Inverse variance weighting (IVW) revealed a negative correlation between and sleep disorders (OR = 0.797, 95% CI = 0.66-0.96, and = 0.016), a positive correlation between and sleep disorders (OR = 1.429, 95% CI = 1.03-1.98, and = 0.032), a negative association between and sleep disorders (OR = 0.745, 95% CI = 0.56-0.98, and = 0.038), and a negative association between and sleep disorders (OR = 0.858, 95% CI = 0.74-0.99, = 0.039).
CONCLUSION
A significant causal relationship was found between four specific gut microbiota and sleep disorders. One family, , was observed to increase the risk of sleep disorders, while three genera, namely, , and , could reduce the risk of sleep disorders. However, further investigations are needed to confirm the specific mechanisms by which the gut microbiota affects sleep.
PubMed: 38585691
DOI: 10.3389/fmicb.2024.1372827 -
Frontiers in Microbiology 2024Several studies have pointed to the critical role of gut microbiota (GM) and their metabolites in Hirschsprung disease (HSCR) pathogenesis. However, the detailed causal...
BACKGROUND
Several studies have pointed to the critical role of gut microbiota (GM) and their metabolites in Hirschsprung disease (HSCR) pathogenesis. However, the detailed causal relationship between GM and HSCR remains unknown.
METHODS
In this study, we used two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between GM and HSCR, based on the MiBioGen Consortium's genome-wide association study (GWAS) and the GWAS Catalog's HSCR data. Reverse MR analysis was performed subsequently, and the sensitivity analysis, Cochran's Q-test, MR pleiotropy residual sum, outlier (MR-PRESSO), and the MR-Egger intercept were used to analyze heterogeneity or horizontal pleiotropy. 16S rDNA sequencing and targeted mass spectrometry were developed for initial validation.
RESULTS
In the forward MR analysis, inverse-variance weighted (IVW) estimates suggested that Eggerthella (OR: 2.66, 95%CI: 1.23-5.74, = 0.01) was a risk factor for HSCR, while Peptococcus (OR: 0.37, 95%CI: 0.18-0.73, = 0.004), Ruminococcus2 (OR: 0.32, 95%CI: 0.11-0.91, = 0.03), Clostridiaceae1 (OR: 0.22, 95%CI: 0.06-0.78, = 0.02), Mollicutes RF9 (OR: 0.27, 95%CI: 0.09-0.8, = 0.02), Ruminococcaceae (OR: 0.16, 95%CI: 0.04-0.66, = 0.01), and Paraprevotella (OR: 0.45, 95%CI: 0.21-0.98, = 0.04) were protective factors for HSCR, which had no heterogeneity or horizontal pleiotropy. However, reverse MR analysis showed that HSCR (OR: 1.02, 95%CI: 1-1.03, = 0.049) is the risk factor for Eggerthella. Furthermore, some of the above microbiota and short-chain fatty acids (SCFAs) were altered in HSCR, showing a correlation.
CONCLUSION
Our analysis established the relationship between specific GM and HSCR, identifying specific bacteria as protective or risk factors. Significant microbiota and SCFAs were altered in HSCR, underlining the importance of further study and providing new insights into the pathogenesis and treatment.
PubMed: 38516012
DOI: 10.3389/fmicb.2024.1366181