An online atlas of human plasma metabolite signatures of gut microbiome composition

Abstract

Human gut microbiota produce a variety of molecules, some of which enter the bloodstream and impact health. Conversely, dietary or pharmacological compounds may affect the microbiota before entering the circulation. Characterization of these interactions is an important step towards understanding the effects of the gut microbiota on health. In this cross-sectional study, we used deep metagenomic sequencing and ultra-high-performance liquid chromatography linked to mass spectrometry for a detailed characterization of the gut microbiota and plasma metabolome, respectively, of 8583 participants invited at age 50 to 64 from the population-based Swedish CArdioPulmonary bioImage Study. Here, we find that the gut microbiota explain up to 58% of the variance of individual plasma metabolites and we present 997 associations between alpha diversity and plasma metabolites and 546,819 associations between specific gut metagenomic species and plasma metabolites in an online atlas (https://gutsyatlas.serve.scilifelab.se/). We exemplify the potential of this resource by presenting novel associations between dietary factors and oral medication with the gut microbiome, and microbial species strongly associated with the uremic toxin p-cresol sulfate. This resource can be used as the basis for targeted studies of perturbation of specific metabolites and for identification of candidate plasma biomarkers of gut microbiota composition.

Characterization of the Cafeteria Diet as Simulation of the Human Western Diet and Its Impact on the Lipidomic Profile and Gut Microbiota in Obese Rats

“…Circulating fatty acids can come from the diet, as substrates for chemical reactions of metabolism, but they can also be derived from the product of bacteria that inhabit the host’s intestine, thus contributing to the pathogenesis of obesity. Thus, alterations in the lipidome may be related to diet-induced changes in bacterial composition and diversity [ 33 ].…”

Small molecule metabolites: discovery of biomarkers and therapeutic targets

“…Metabolome is affected by genetic factors, intestinal flora and environmental exposures. 817 – 820 These changes might originate from the environment, physiological or pathological status, diseases, drugs or other external stimuli, which can significantly contribute to the metabolome composition. Moreover, small molecule metabolites-based metabolomics can identify as many marker metabolites as possible and then reveal the metabolic network associations of bioactive substances and effective targets, needs to validate these associations, and further mechanistic research on dysregulated metabolites should be implemented and reproduced.…”

Gut Microbiome Composition in Patients with Chronic Urticaria: A Review of Current Evidence and Data

“…Knowledge about metabolites’ biochemical functions could help us better understand host-gut microbiota interactions. Human phenotype is modulated by the gut microbiome, which was recently found to explain up to 58% of individual plasma metabolite variance [ 51 ]. Thus, the gut microbiome is composed of diverse microorganisms that have a protective and structural role in the gut and that also carry out some essential metabolic functions, including the synthesis of amino acids, biotransformation of bile acids and the production of short-chain fatty acids [ 52 ].…”