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Trimethylamine-N-oxide (TMAO) is gut microbiota-derived metabolite, plays a critical role in human health and diseases such as metabolic, cardiovascular, colorectal cancer and, neurological disorders. Binding interactions between TMAO and serum albumins are crucial to understand the impact of TMAO on disease mechanisms. However, detailed insights into the interaction mechanisms, preferred binding locations, and conformational changes in BSA upon binding TMAO are still unclear. TMAO interacts with serum albumin in human body and thus, a model study of interaction for TMAO-BSA conjugate is presented in support of it. Decrease in absorbance intensity of protein upon interaction with metabolites reveals conjugate formation, while fluorescence spectroscopy indicate static quenching. Contact angle measurements further reveal the hydrophilic nature of the TMAO-BSA complex, while CD and FTIR support conformational changes in BSA upon binding but structure remain intact. Computational studies, such as molecular docking, molecular dynamics simulation and, MM/GBSA, confirm a stable complex with a binding energy of − 3.6 kcal/mol. These findings provide a foundation for understanding the pharmacodynamics and pharmacokinetics of TMAO and may aid in developing strategies for treating diseases, such as chronic kidney disease and neurological disorder where TMAO-serum albumins interaction are implicated. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of ulcerative colitis (UC) today is limited to a small number of biomarkers. Trimethylamine-N-oxide (TMAO) is the product of reactions resulting from the degradation of dietary-free choline, phosphatidylcholine, and carnitine metabolism by the intestinal microbiota. Earlier studies showed his involvement in the pathogenesis of UC. To study the association of TMAO with clinical, laboratory, and endoscopic indicators of UC activity. Methods: an observational cross-sectional comparative study was conducted based on the NCJSC "KMU" clinic, Karaganda, Kazakhstan. High-performance liquid chromatography measured TMAO concentration in 63 patients with UC (age Me 37 (30-52) and 38 healthy individuals (age Me 38 (28.5-49.5). Results: Median TMAO level in patients with UC-0.286 μmol/l was significantly lower than in the control group Me 0.646 μmol/l (p<0.0001). TMAO had significant differences in groups with clinically active and inactive colitis (P=0.003). TMAO correlated with disease activity by Montreal scale (r=-0.389, P=0.002) and severity of attack by Truelove-Witts (r=-0.301, P=0.027 respectively), patient's age (r=0.377, P=0.003), stool frequency (r=-0.427, P=0.001); laboratory parameters: WBC (r=-0.31, P=0.042), blood albumin (r=0.379, P=0.002) and fecal calprotectin (r=-0.314, P=0.022). TMAO did not differ between groups divided by the extent of the pathological process and endoscopic activity. Conclusion: in patients with UC, TMAO levels decrease compared with healthy individuals and differences in groups depend on the disease activity. These results give reason to consider changes in TMAO levels as a potential marker of UC and the severity of its course. [ABSTRACT FROM AUTHOR]

Abstract Background Trimethylamine N-oxide (TMAO) is a metabolite produced by gut microbiota, and its potential impact on lipid metabolism in mammals has garnered widespread attention in the scientific community. Bovine fatty liver disease, a metabolic disorder that severely affects the health and productivity of dairy cows, poses a significant economic burden on the global dairy industry. However, the specific role and pathogenesis of TMAO in bovine fatty liver disease remain unclear, limiting our understanding and treatment of the condition. This study aims to construct a bovine fatty liver cell model using an integrated approach that combines transcriptomic, proteomic, and metabolomic data. The objective is to investigate the impact of TMAO on lipid metabolism at the molecular level and explore its potential regulatory mechanisms. Results We established an in vitro bovine fatty liver cell model and conducted a comprehensive analysis of cells treated with TMAO using high-throughput omics sequencing technologies. Bioinformatics methods were employed to delve into the regulatory effects on lipid metabolism, and several key genes were validated through RT-qPCR. Treatment with TMAO significantly affected 4790 genes, 397 proteins, and 137 metabolites. KEGG enrichment analysis revealed that the significantly altered molecules were primarily involved in pathways related to the pathology of fatty liver disease, such as metabolic pathways, insulin resistance, hepatitis B, and the AMPK signaling pathway. Moreover, through joint analysis, we further uncovered that the interaction between TMAO-mediated AMPK signaling and oxidative phosphorylation pathways might be a key mechanism promoting lipid accumulation in the liver. Conclusions Our study provides new insights into the role of TMAO in the pathogenesis of bovine fatty liver disease and offers a scientific basis for developing more effective treatment strategies.

Atherosclerosis (AS) is a cardiovascular disease caused by excessive accumulation of lipids in arterial walls. In this study, we developed an AS model in ApoE−/− mice using a high-fat, high-cholesterol diet and investigated the anti-AS mechanism of aged garlic oligosaccharides (AGOs) by focusing on the gut microbiota. Results revealed that AGOs exhibited significant anti-AS effects, reduced trimethylamine N-oxide levels from 349.9 to 189.2 ng/mL, and reduced aortic lipid deposition from 31.7 % to 9.5 %. AGOs significantly increased the levels of short-chain fatty acids in feces, in which acetic, propionic, and butyric acids were increased from 1.580, 0.364, and 0.469 mg/g to 2.233, 0.774, and 0.881 mg/g, respectively. An analysis of the gut microbiota indicated that AGOs restored alpha and beta diversity, decreased the Firmicutes/Bacteroidetes ratio, and promoted the dominance of the genus Akkermansia. A metagenomic analysis revealed that AGOs alleviated AS through the ABC transporter pathway and the lipopolysaccharide biosynthesis pathway. • AGO reduced serum lipid levels and aortic lipid deposition in atherosclerosis mice. • AGO reduced serum TMAO levels and increases fecal SCFAs levels in AS mice. • AGO achieved its anti-AS effect by modulating the gut microbiota in AS mice. • AGO mitigated AS by upregulating the ABC transporter pathway. • AGO mitigated AS by downregulating the lipopolysaccharide biosynthesis pathway. [ABSTRACT FROM AUTHOR]