The human gut microbiome plays a major role in diet and health, but standard profiling using 16S genes does not show the whole picture on gut metabolic functions. To directly investigate these metabolic functions, a team led by researchers from King's College London have profiled the gut metabolomes of hundreds of individuals--the largest study of its kind. Their recently published paper in Nature Genetics sheds new insights on host-microbe interactions and obesity.

'This study has really accelerated our understanding of the interplay between what we eat, the way it is processed in the gut and the development of fat in the body, but also immunity and inflammation,” said study lead author Cristina Menni. “By analysing the faecal metabolome, we have been able to get a snapshot of both the health of the body and the complex processes taking place in the gut.”

The team analyzed the stool samples of 786 individuals (from a population-based twin study). From these samples, the team identified biomarkers that associated with the build-up of internal fat around the waist. Visceral fat is understood to be strongly associated with the development of conditions including type 2 diabetes, heart disease, and obesity.

The team also identified 1,116 chemical metabolites that were used to build a gut metabolome bank. Analysis of the metabolites revealed that less than a fifth (17.9 percent of heritability) of gut processes in terms of the metabolome could be attributed to hereditary factors. Instead, the metabolome more closely reflected the gut microbial composition (67.7 percent). The team also found that it also strongly associated with the mass of the visceral fat.

“This new knowledge means we can alter the gut environment and confront the challenge of obesity from a new angle that is related to modifiable factors such as diet and the microbes in the gut,” said first author Jonas Zierer. “This is exciting, because unlike our genes and our innate risk to develop fat around the belly, the gut microbes can be modified with probiotics, with drugs or with high fibre diets.”

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From these findings, the team concluded that the fecal metabolome illustrates potential mechanisms that underlie obesity. Moreover, metabolome profiling could serve as a novel tool to explore links among microbiome composition, host phenotypes, and heritable complex traits.