The relationship between gut microbiome and trimethylamine oxide (TMAO) has not been fully elucidated. We aimed to assess the causal effects of different gut microbes on TMAO using Mendelian randomization (MR).

Gut microbiome and TMAO datasets were acquired from genome-wide association studies and screened for single nucleotide polymorphisms according to the basic assumptions of MR. Inverse variance weighted was used as the main method in MR analysis to assess the causal relationship between the gut microbiome and TMAO. Finally, the MR-Egger intercept, Cochran's Q test, and leave-one-out sensitivity analysis were used to assess the horizontal pleiotropy, heterogeneity, and robustness of the results, respectively.

MR analysis revealed that the species Bacteroides finegoldii (odds ratio [OR] 1.064, 95% confidence interval [CI] 1.003 to 1.128, p = 0.039), family Sutterellaceae (OR 1.188, 95% CI 1.003 to 1.407, p = 0.047), and phylum Pseudomonadota (OR 1.205, 95% CI 1.036 to 1.401, p = 0.016), as well as the species Bacteroides uniformis (OR 1.263, 95% CI 1.039 to 1.535, p = 0.019), were positively associated with increased genetic susceptibility to TMAO. In contrast, the species Bacteroides thetaiotaomicron (OR 0.813, 95% CI 0.696 to 0.950, p = 0.009) and Bilophila wadsworthia (OR 0.828, 95% CI 0.690 to 0.995, p = 0.044) were associated with reduced genetic susceptibility to TMAO. Additionally, the MR-Egger intercept indicated no horizontal pleiotropy (p ≥ 0.05), and Cochran's Q test and sensitivity analysis demonstrated that the results were not heterogeneous (p ≥ 0.05) and were robust.

Our findings revealed the role of the phylum Pseudomonadota, family Sutterellaceae, species Bacteroides finegoldii, and Bacteroides uniformis in increasing TMAO, as well as the species Bacteroides thetaiotaomicron and Bilophila wadsworthia in decreasing TMAO. This study provides new insights into the relationship between the gut microbiome and TMAO levels.

Respiratory tuberculosis (RTB), a global health concern affecting millions of people, has been observationally linked to the gut microbiota, but the depth and nature of this association remain elusive. Despite these findings, the underlying causal relationship is still uncertain. Consequently, we used the Mendelian randomization (MR) method to further investigate this potential causal connection. We sourced data on the gut microbiota from a comprehensive genome-wide association study (GWAS) conducted by the MiBioGen Consortium (7686 cases, and 115,893 controls). For RTB, we procured 2 distinct datasets, labeled the Fingen R9 TBC RESP and Fingen R9 AB1 RESP, from the Finnish Genetic Consortium. To decipher the potential relationship between the gut microbiota and RTB, we employed MR on both datasets. Our primary mode of analysis was the inverse variance weighting (IVW) method. To ensure robustness and mitigate potential confounders, we meticulously evaluated the heterogeneity and potential pleiotropy of the outcomes. In the TBC RESP (RTB1) dataset related to the gut microbiota, the IVW methodology revealed 7 microbial taxa that were significantly associated with RTB. In a parallel vein, the AB1 RESP (RTB2) dataset highlighted 4 microbial taxa with notable links. Notably, Lachnospiraceae UCG010 was consistently identified across both datasets. This correlation was especially evident in the data segments designated Fingen R9 TBC RESP (OR = 1.799, 95% CI = 1.243-2.604) and Finngen R9 AB1 RESP (OR = 2.131, 95% CI = 1.088-4.172). Our study identified a causal relationship between particular gut microbiota and RTB at the level of prediction based on genetics. This discovery sheds new light on the mechanisms of RTB development, which are mediated by the gut microbiota.

The coexistence of coronary artery disease (CAD) and cognitive impairment has become a common clinical phenomenon. However, there is currently limited research on the etiology of this disease cluster, discovery of biomarkers, and identification of precise intervention targets.

We explored the causal connections between gut microbiota, blood metabolites, and the disease cluster of CAD combined with cognitive impairment through two-sample Mendelian randomization (TSMR). Additionally, we determine the gut microbiota and blood metabolites with the strongest causal associations using Bayesian model averaging multivariate Mendelian randomization (MR-BMA) analysis. Furthermore, we will investigate the mediating role of blood metabolites through a two-step Mendelian randomization design.

We identified gut microbiota that had significant causal associations with cognitive impairment. Additionally, we also discovered blood metabolites that exhibited significant causal associations with both CAD and cognitive impairment. According to the MR-BMA results, the free cholesterol to total lipids ratio in large very low density lipoprotein (VLDL) was identified as the key blood metabolite significantly associated with CAD. Similarly, the cholesteryl esters to total lipids ratio in small VLDL emerged as the primary blood metabolite with a significant causal association with dementia with lewy bodies (DLB). For the two-step Mendelian randomization analysis, we identified blood metabolites that could potentially mediate the association between genus Butyricicoccus and CAD in the potential causal links.

Our study utilized Mendelian randomization (MR) to identify the gut microbiota features and blood metabolites characteristics associated with the disease cluster of CAD combined with cognitive impairment. These findings will provide a meaningful reference for the identification of biomarkers for the disease cluster of CAD combined with cognitive impairment as well as the discovery of targets for intervention to address the problems in the clinic.

Coronary artery disease (CAD), a primary component of cardiovascular diseases, is one of the top contributors to mortality rates worldwide. In 2021, dietary risk was estimated to be attributed to 6.58 million cardiovascular deaths. Plant-based diets (PBDs), which encourage higher consumption of plant foods and lower intake of animal-based foods, have been shown to reduce the risk of CAD by up to 29% when compared to non-vegetarian diets in a meta-analysis. This article aims to summarize the array of PBDs and compare them with conventional Western diets that include meat. We review the various proposed mechanisms for how the bioactive nutrients of PBDs aid in preventing atherosclerosis and CAD events, as well as other cardiac diseases. We conducted a detailed search of PubMed using our exclusive search strategy using the keywords plant-based diet, vegan diet, phytosterols, CAD, myocardial ischemia, and atherosclerosis. A total of 162 pertinent articles published within the past decade were identified for qualitative synthesis. To ensure the accuracy and reliability of our review, we included a total of 55 full-text, peer-reviewed articles that demonstrated the effects of plant-based diets on CAD and were written in English. We excluded animal studies, in vitro or molecular studies, and non-original data like editorials, letters, protocols, and conference abstracts. In this article, we emphasize the importance of dietary interventions, such as PBDs, to prevent CAD and their benefits on environmental sustainability. Integrating plant foods and whole grains into one's daily eating habits leads to an increase in the intake of nutrient-rich foods while reducing the consumption of processed food could not only prevent millions of premature deaths but also provide prevention against many chronic gastrointestinal and metabolic diseases.