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BMC Cardiovascular Disorders Mar 2024Recent studies have indicated an association between intestinal flora and lipids. However, observational studies cannot indicate causality. In this study, we aimed to...
AIMS
Recent studies have indicated an association between intestinal flora and lipids. However, observational studies cannot indicate causality. In this study, we aimed to investigate the potentially causal relationships between the intestinal flora and blood lipids.
METHODS
We performed a bidirectional two-sample Mendelian Randomization (MR) analysis to investigate the causal relationship between intestinal flora and blood lipids. Summary statistics of genome-wide association studies (GWASs) for the 211 intestinal flora and blood lipid traits (n = 5) were obtained from public datasets. Five recognized MR methods were applied to assess the causal relationship with lipids, among which, the inverse-variance weighted (IVW) regression was used as the primary MR method. A series of sensitivity analyses were performed to test the robustness of the causal estimates.
RESULTS
The results indicated a potential causal association between 19 intestinal flora and dyslipidemia in humans. Genus Ruminococcaceae, Christensenellaceae, Parasutterella, Terrisporobacter, Parabacteroides, Class Erysipelotrichia, Family Erysipelotrichaceae, and order Erysipelotrichales were associated with higher dyslipidemia, whereas genus Oscillospira, Peptococcus, Ruminococcaceae UCG010, Ruminococcaceae UCG011, Dorea, and Family Desulfovibrionaceae were associated with lower dyslipidemia. After using the Bonferroni method for multiple testing correction, Only Desulfovibrionaceae [Estimate = -0.0418, 95% confidence interval [CI]: 0.9362-0.9826, P = 0.0007] exhibited stable and significant negative associations with ApoB levels. The inverse MR analysis did not find a significant causal effect of lipids on the intestinal flora. Additionally, no significant heterogeneity or horizontal pleiotropy for IVs was observed in the analysis.
CONCLUSION
The study suggested a causal relationship between intestinal flora and dyslipidemia. These findings will provide a meaningful reference to discover dyslipidemia for intervention to address the problems in the clinic.
Topics: Humans; Gastrointestinal Microbiome; Genome-Wide Association Study; Mendelian Randomization Analysis; Atherosclerosis; Dyslipidemias
PubMed: 38431594
DOI: 10.1186/s12872-024-03804-3 -
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 Medicine 2024The etiological factors of Cholestatic Liver Diseases especially primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are not fully illustrated. It...
BACKGROUND
The etiological factors of Cholestatic Liver Diseases especially primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are not fully illustrated. It has been reported in previous observational studies that gut microbiota are associated with cholestatic liver diseases. However, there is uncertainty regarding the causality of this association. By using Mendelian randomization, this study aimed to examine the causal impact of gut microbiota on cholestatic liver diseases.
METHODS
From large-scale genome-wide association studies, genetic instruments for each gut microbiota taxa as well as primary biliary cholangitis and primary sclerosing cholangitis were developed. Subsequently, we conducted a two-sample Mendelian randomization analysis, supplemented by multiple sensitivity analyses. Additionally, we performed reverse MR analyses to investigate the possibility of the reverse causal association.
RESULT
This two-sample MR study indicated that the was associated with a decreased risk of developing PBC, and that may be factors that increase the risk of PBC. On the other hand, we also identified were positively associated with PSC. The , and were found negative associations with the risk of PSC. The reverse MR analysis demonstrated no statistically significant relationship between PBC, PSC and these specific gut microbial taxa.
CONCLUSION
Our findings offered novel evidence that the abundance of particular bacteria contributes to the risk of PBC and PSC, which may contribute to more effective approaches to PBC and PSC therapy and prevention.
PubMed: 38327703
DOI: 10.3389/fmed.2024.1342119 -
Frontiers in Microbiology 2024The associations between gut microbiota and cardiovascular disease have been reported in previous studies. However, the relationship between gut microbiota and...
BACKGROUND
The associations between gut microbiota and cardiovascular disease have been reported in previous studies. However, the relationship between gut microbiota and endocarditis remains unclear.
METHODS
A bidirectional Mendelian randomization (MR) study was performed to detect the association between gut microbiota and endocarditis. Inverse variance weighted (IVW) method was considered the main result. Simultaneously, heterogeneity and pleiotropy tests were conducted.
RESULTS
Our study suggests that family Victivallaceae ( = 0.020), genus group ( = 0.047), genus Escherichia Shigella ( = 0.024), genus Peptococcus ( = 0.028) and genus Sellimonas ( = 0.005) play protective roles in endocarditis. Two microbial taxa, including genus Blautia ( = 0.006) and genus Ruminococcus2 ( = 0.024) increase the risk of endocarditis. At the same time, endocarditis has a negative effect on genus group ( = 0.048). Besides, no heterogeneity or pleiotropy was found in this study.
CONCLUSION
Our study emphasized the certain role of specific gut microbiota in patients with endocarditis and clarified the negative effect of endocarditis on gut microbiota.
PubMed: 38298894
DOI: 10.3389/fmicb.2024.1320095 -
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 -
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 -
BMC Microbiology Dec 2023Certain strains of probiotic bacteria can secret functional substances namely digestive enzymes and functional peptides to regulate physiological conditions such as...
Certain strains of probiotic bacteria can secret functional substances namely digestive enzymes and functional peptides to regulate physiological conditions such as digestion and anti-oxidation, which are often incorporated in industrial broiler chick production. However, few studies have detailed the action mechanisms and effects of these bacteria on regulating growth and anti-oxidation levels in broiler chickens. Ligilactobacillus salivarius is a strain of probiotic bacteria used as dietary supplement. In the present study, Ligilactobacillus salivarius was evaluated for its secreted digestive enzymes in vitro. To detailed evaluate the action mechanisms and effects of gastrointestinal tract (GIT) microbiota on alleviating anti-oxidation levels of broiler chickens through the gut-brain axis. Ligilactobacillus salivarius was cultured and supplemented in the food of broilers to evaluate the probiotic effect on growth and anti-oxidation by modulation of gut microbial composition and its functional metabolites using metagenomic and metabolomic assays. Biochemical results showed that Ligilactobacillus salivarius secreted digestive enzymes: protease, lipase, and amylase. Broiler chickens with Ligilactobacillus salivarius supplemented for 42 days, showed increased body weights, a reduced oxidative status, decreased malondialdehyde levels, and improved activities rates of total superoxide dismutase, glutathione peroxidase IIand IV improved. The microbial composition of caecum was more abundant than those broiler without probiotics supplementation, owing 400 of total number (489) of bacterial operational taxonomic units (OTU). The genera of Lactobacillus, Megamonas, Ruminoccoccaceae, Ruminococcus, Alistipes and Helicobacter shared the dominant proportion of Candidatus _Arthromitus compared with the control chickens. These functional bacteria genera assisted in the transportation and digestion of amino acids, carbohydrates, and ions, synthesis of cellular membranes, and anti-oxidation. Uncultured_organism_g_ Anaerosporobacter, Lactobacillus salivarius, uncultured_bacterium_g_ Ruminococcaceae_UCG-014, uncultured_bacterium_g_ Peptococcus were strongly and positively correlated with body growth performance and anti-oxidation. A metabonomic assay suggested that the secreted of gamma-aminobutyric acid and monobactam was metabolized according to the Kyoto Encyclopedia of Genes and Genomes analysis. In conclusion, Ligilactobacillus salivarius optimized microbial composition of the caecum and secreted functional peptides through gut-brain axis to improve the body growth and antioxidation of broiler chicken.
Topics: Animals; Ligilactobacillus salivarius; Chickens; Brain-Gut Axis; Animal Feed; Probiotics; Bacteria; Peptides
PubMed: 38071295
DOI: 10.1186/s12866-023-03135-x -
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 Veterinary Science 2023The current trend of dog owners increasingly favoring the functional value of food to assure preventive health and wellbeing of their pets has been raising the interest...
The current trend of dog owners increasingly favoring the functional value of food to assure preventive health and wellbeing of their pets has been raising the interest in microalgae as natural additives with bioactive properties. However, scientific studies addressing the effects of microalgae supplementation in diets for dogs are scarce. This study aimed to evaluate the effects of dietary supplementation with three microalgae species (, , and ) on diet palatability, total tract digestibility, metabolizable energy content, fecal metabolites and microbiota of dogs. Twelve adult Beagle dogs were used in three two-bowl tests to compare the palatability of a commercial complete diet for adult dogs without (reference diet) and with 1.5% supplementation of each microalgae. From the results obtained, three digestibility trials were performed according to a replicated Latin square 3 × 3, with six adult Beagle dogs, three experimental periods of 10 days each, and three dietary supplementation levels of microalgae (0.5, 1.0, and 1.5%). In each trial, effects of microalgae supplementation levels on total tract digestibility, metabolizable energy content, fecal metabolites and microbiota of dogs were evaluated. First diet approached or tasted was not significantly affected by microalgae inclusion, but dogs showed a preference for the reference diet over the diets with 1.5% inclusion of and , no difference being observed with 1.5% . In all digestibility trials, dietary supplementation with microalgae up to 1.5% did not greatly affected the dietary chemical composition and kept unaffected food intake, fecal output and metabolites, and digestibility of nutrients and energy. Compared with the reference diet, supplementation with increased protein digestibility. Fecal characteristics and metabolites were affected by microalgae supplementation, being the effects dependent on the species. Fecal microbiota composition of dogs fed with microalgae-supplemented diets was modified by promoting the beneficial and genera associated with gut health and activation of the immune system. Overall, the results support , , and as sustainable functional supplements that potentially enhance gastrointestinal health of dogs through the selective stimulation of microbiota without detrimental effects on food intake and digestibility.
PubMed: 37829353
DOI: 10.3389/fvets.2023.1245790 -
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