Measurement of gut microbial metabolites in cardiometabolic health and translational research

Abstract

The human gut microbiota is a functioning endocrine organ and stands at the intersection between dietary components and health or disease. There are very many microbial metabolites with numerous structures and functions arising from the gut microbial fermentation of foods and become signals for biological communication in the human body. These small molecules can be absorbed and delivered to distant organs through the circulatory system to build the gut–systemic axis. The gut microbial metabolomes are thus believed to play important roles in regulating cardiometabolic health and provide opportunities in mechanistic research and new drug discovery. Measurement of these novel microbial metabolites in clinical samples may serve as a tool for investigating disease biomarkers. In the past decade, the development of untargeted and targeted metabolomics approaches using NMR, LC/MS, and GC/MS has contributed to the exploration of gut microbial metabolomes in cardiometabolic health and disease. Some important targets are currently being translated into clinical applications. In this review article, we introduce an oral carnitine challenge test developed as an example to demonstrate the potential applications in personalized nutrition based on the function of gut microbiota. It is a method taking the gut microbiota as a bioreactor and provides fermentable materials as inputs and measures the outputs of targeted microbial byproducts in the blood or urine. This challenge test may be extended to measure metabolites from microbial fermentation related to other endocrinological or inflammatory diseases. We review current gut metabolome research approaches and propose a gut microbial functional measurement using a challenge test. We suggest that the maturation in measuring gut microbial metabolites may provide an important piece to complete the puzzle of precision medicine.

Characterization of TMAO productivity from carnitine challenge facilitates personalized nutrition and microbiome signatures discovery

“…Complexed interactions exist between foods, gut microbiota, and the host, which include the competition between human cells and gut microbes to absorb and utilize dietary ingredients from foods. Some beneficial nutrients or even drugs may be utilized by gut microbes to produce harmful metabolites for the human body [2][3][4]. For example, trimethylamine (TMA) is a microbiota-derived metabolite from dietary carnitine and choline, and its host-modified product, trimethylamine N-oxide (TMAO), was recently found to be highly correlated with cardiovascular disease (CVD) [5].…”

Gut microbiota: a promising target against cardiometabolic diseases

“…It is likely that many yet to be identified microbiota-derived metabolites influence host metabolism. As these intestinal metabolites are presumably present in big numbers, research methods that allow comprehension of big numbers and complex metabolite patterns such as untargeted metabolomics analysis are necessary to find new drug targets to customize the treatment of CMD [72]. To identify new metabolites that influence host metabolism, various body samples can be studied such as organ tissue, blood plasma or serum, feces, urine, saliva cerebrospinal fluid, and exhaled breath [73].…”

Biomarkers of a Healthy Nordic Diet—From Dietary Exposure Biomarkers to Microbiota Signatures in the Metabolome

“…The impact of the gut microbiota on the human host is mostly mediated via molecules originating from the diet or endogenous metabolism and which are processed in the metabolism of the gut bacteria. These compounds enter the circulation and subsequently the target organs and they offer a possibility to measure the biochemical activity of the gut microbiota and, to some extent, its composition [77,78]. As such, they may serve as indicators that reflect gut microbiota composition, specific food intakes or the interaction between diet and gut microbiota related to specific health-related metabolic traits.…”