Xenometabolomics reveals metabolic functional guilds unique to specific inulin subtypes in human gut microbiota cultures

Authors: PICCOLO, BRIAN - Arkansas Children'S Nutrition Research Center (ACNC); CHEN, MING-HSU - Purdue University; LAN, RENNY - Arkansas Children'S Nutrition Research Center (ACNC); MOODY, BECKY - Arkansas Children'S Nutrition Research Center (ACNC); YAO, TIANMING - Purdue University; HUANG, TING-YI - Nanyang Technological University; PACK, LINDSAY - Arkansas Children'S Nutrition Research Center (ACNC); ADAMS, SEAN - University Of California, Davis; LINDEMANN, STEPHEN - Purdue University

Submitted to: mSystems
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/9/2025
Publication Date: 8/28/2025
Citation: Piccolo, B.D., Chen, M., Lan, R.S., Moody, B., Yao, T., Huang, T., Pack, L., Adams, S.H., Lindemann, S.R. 2025. Xenometabolomics reveals metabolic functional guilds unique to specific inulin subtypes in human gut microbiota cultures. mSystems. https://doi.org/10.1128/msystems.01031-25.
DOI: https://doi.org/10.1128/msystems.01031-25

Interpretive Summary: Eating different kinds of dietary fiber affects our microbiota, the bacteria that live in our guts, which can in turn affect our overall health. How these dietary fibers, found in fruits, vegetables, and grains, help beneficial gut bacteria grow and how these fibers break down into other bioactive metabolites that benefit the body is an area of growing research. We know that when people eat a variety of fibers, the types of bacteria that make up their microbiota change in healthy ways. Still, two people eating the same high-fiber food might have very different types of bacteria that grow in their gut. Gut bacteria break down dietary fibers into short-chain fatty acids and other potentially beneficial metabolites, which can reduce inflammation, strengthen the gut barrier, and support the immune system. The type of fiber eaten determines what types of bioactive metabolites are created by our gut bacteria. Investigators, including ACNC scientists, used metabolomics to characterize how different human microbiota types break down six different types of inulin fibers. Regardless of microbiota type, each of the fiber types were uniquely metabolized similarly across individuals. This suggests that people can still get the health benefits of fibers even when they have different types of bacteria in their gut. This work highlights that dietary fiber plays a role in keeping humans healthy—supporting the recommendations to eat a balanced diet rich in many plant-based fibers. This work also suggests that future nutrition plans could be personalized based on a person’s gut microbiome and help clinicians suggest targeted diets or specific foods to better support gut and overall health.

Technical Abstract: Dietary fibers promote positive health outcomes that are generally attributed to large bowel bacterial fermentation and associated bioactive metabolites. Historically, studies of the latter have focused on short-chain fatty acids such as butyrate. The gastrointestinal microbiota generate thousands of xenometabolites (microbe-derived, “non-host” metabolites). Most remain uncharacterized for composition and potential bioactivity, and little is known about the impact of fiber structure on the xenometabolome. Using LC/MS, we characterized culture supernatant metabolite profiles in human stool lineages derived from three healthy adult donors and six inulins covering a range of degrees of polymerization (DPs): chicory-derived Frutalose L90 (L90; DP ~ 3), Alfa Aesar (AA; DP ~ 5), Frutafit CLR (CLR; DP ~ 8), Frutafit IQ (IQ; DP ~ 12), Frutafit TEX (TEX; DP > 23), and the highly branched Frutafit agave inulin (AGA). Of the 1,219 LC/MS detected metabolites included in the final data analysis, concentrations of 704 were statistically significant (FDR < 0.1; Kruskal-Wallis test). Of these, 15 metabolites had a structural annotation, highlighting the large number of “unknown” xenometabolites associated with inulin substrates. Each fiber type led to distinct metabolite signatures, despite lineages displaying highly disparate microbial community structures within and across donors. This illustrates that fiber-specific metabolic functional guilds manifest despite highly diverse human gut bacteria communities. While speculative, these metabolic functional guilds could help explain why health effects of dietary fibers are prevalent across the population despite highly disparate gut microbiota patterns. The results also reinforce that fiber structures have a profound effect on the xenometabolome.