Gut microbial metabolites reveal diet-dependent metabolic changes induced by nicotine administration.

The gut microbiota has emerged as an important factor that potentially influences various physiological functions and pathophysiological processes such as obesity and type 2 diabetes mellitus. Accumulating evidence from human and animal studies suggests that gut microbial metabolites play a critical role as integral molecules in host-microbe interactions. Notably, several dietary environment-dependent fatty acid metabolites have been recognized as potent modulators of host metabolic homeostasis. More recently, nicotine, the primary active molecule in tobacco, has been shown to potentially affect host metabolism through alterations in the gut microbiota and its metabolites. However, the mechanisms underlying the interplay between host nutritional status, diet-derived microbial metabolites, and metabolic homeostasis during nicotine exposure remain unclear. Our findings revealed that nicotine administration had potential effects on weight regulation and metabolic phenotype, independent of reduced caloric intake. Moreover, nicotine-induced body weight suppression is associated with specific changes in gut microbial composition, including Lactobacillus spp., and KetoB, a nicotine-sensitive gut microbiota metabolite, which could be linked to changes in host body weight, suggesting its potential role in modulating host metabolism. Our findings highlight the remarkable impact of the interplay between nutritional control and the gut environment on host metabolism during smoking and smoking cessation.

Trimethylamine N-oxide and risk of inflammatory bowel disease: A Mendelian randomization study.

A previous study suggested that inflammatory bowel disease (IBD) patients have low plasma levels of trimethylamine N-oxide (TMAO). In the present study, we examined this hypothesis using Mendelian randomization analysis. We used summary statistics data for single-nucleotide polymorphisms associated with plasma levels of TMAO, and the corresponding data for IBD from a genome-wide association meta-analysis of 59,957 individuals (25,042 diagnosed IBD cases, 34,915 controls). The association between genetically predicted plasma TMAO levels and IBD showed odds ratios (95% confidence interval [CI]) per 1 interquartile range increment (per 2.4 µmol/L) in TMAO levels were 0.91 (0.81-1.01, P = .084) for IBD, 0.88 (0.76-1.02, P = .089) for ulcerative colitis, 0.91 (0.79-1.05, P = .210) for Crohn disease. There was no evidence for pleiotropy based on the Mendelian randomization-Egger regression analyses (P-intercept = 0.669 for IBD). Further investigations would be needed to understand the causal relationship between TMAO and IBD.

Polyunsaturated fatty acids and risk of anorexia nervosa: A Mendelian randomization study.

PURPOSE: Observational studies have suggested that polyunsaturated fatty acids (PUFAs) decrease the risk of anorexia nervosa (AN). In the present study, we examined this hypothesis using a Mendelian randomization analysis. METHODS: We used summary statistics for single-nucleotide polymorphisms associated with plasma levels of n-6 (linoleic acid and arachidonic acid) and n-3 PUFAs (alpha-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) and the corresponding data for AN from a genome-wide association meta-analysis of 72,517 individuals (16,992 diagnosed AN cases and 55,525 controls). RESULTS: None of the genetically predicted PUFAs were significantly associated with the risk of AN; odds ratios (95 % confidence interval) per 1 standard deviation increase in PUFA levels were 1.03 (0.98, 1.08) for linoleic acid, 0.99 (0.96, 1.03) for arachidonic acid, 1.03 (0.94, 1.12) for alpha-linolenic acid, 0.98 (0.90, 1.08) for eicosapentaenoic acid, 0.96 (0.91, 1.02) for docosapentaenoic acid, and 1.01 (0.90, 1.36) for docosahexaenoic acid. LIMITATION: Only two types of fatty acids (LA and DPA) can be used for pleiotropy tests using the MR-Egger intercept test. CONCLUSION: This study does not support the hypothesis that PUFAs decrease the risk of AN.