Exploring changes in the human gut microbiota and microbial-derived metabolites in response to diets enriched in simple, refined, or unrefined carbohydrate-containing foods: a post hoc analysis of a randomized clinical trial

Authors: FAITS, TYLER - Boston University Medical School; WALKER, MAURA - Boston University Medical School; RODRIGUEZ-MORATO, JOSE - Pompeu Fabra University; MENG, HUICUI - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; GERVIS, JULIE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; GALLUCCIO, JEAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; LICHTENSTEIN, ALICE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; JOHNSON, W - Boston University Medical School; MATTHAN, NIRUPA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/14/2020
Publication Date: 9/16/2020
Citation: Faits, T., Walker, M.E., Rodriguez-Morato, J., Meng, H., Gervis, J., Galluccio, J.M., Lichtenstein, A.H., Johnson, W.E., Matthan, N. 2020. Exploring changes in the human gut microbiota and microbial-derived metabolites in response to diets enriched in simple, refined, or unrefined carbohydrate-containing foods: a post hoc analysis of a randomized clinical trial. The American Journal of Clinical Nutrition. https://doi.org/10.1093/ajcn/nqaa254.
DOI: https://doi.org/10.1093/ajcn/nqaa254

Interpretive Summary: Studies have shown that consuming diets rich in unrefined carbohydrates (whole grains and fiber) have favorable effects on heart disease risk factors. In contrast, the consumption of simple-carbohydrate (e.g. sucrose, high fructose corn syrup), and refined-carbohydrate (e.g. white rice, bread/pasta made from white flour), is generally associated with poor cardiometabolic health. It has been suggested that these effects are mediated by the gut microbiome and metabolites produced by the microbes, such as secondary bile acids (SBA) and short chain fatty acids (SCFA). To address this, we conducted a randomized controlled crossover design intervention study in older men and post-menopausal women who were fed 3 identical diets that differed only in the type of carbohydrate (simple, refined or unrefined). We found that consuming the unrefined carbohydrate-rich diet had modest beneficial effects on the gut microbiome (composition and function) and fecal SBA but not SCFA fecal concentrations. This resulted in favorable changes in some of the heart disease risk factors. Additionally, the simple carbohydrate diet had unique effects on gut microbiota composition that were distinct from refined carbohydrate, suggesting differential mechanisms mediate their effects on cardiometabolic health. These findings provide novel information on potential mechanisms linking carbohydrate type (quality) to human health.

Technical Abstract: Background: Dietary carbohydrate type may influence cardiometabolic risk through alterations in the gut microbiome and microbial-derived metabolites, but evidence is limited. Objectives: We explored the relative effects of an isocaloric exchange of dietary simple, refined, and unrefined carbohydrate on gut microbiota composition/function, and selected microbial metabolite concentrations. Methods: Participants [n = 11; age: 65 +\- 8 y; BMI (in kg/m^2): 29.8 +\-3.2] were provided with each of 3 diets for 4.5 wk with 2-wk washout, according to a randomized, crossover design. Diets [60% of energy (%E) carbohydrate, 15%E protein, and 25%E fat] differed in type of carbohydrate. Fecal microbial composition, metatranscriptomics, and microbial-derived SCFA and secondary bile acid (SBA) concentrations were assessed at the end of each phase and associated with cardiometabolic risk factors (CMRFs). Results: Roseburia abundance was higher (11% compared with 5%) and fecal SBA concentrations were lower (lithocolic acid -50% and deoxycholic acid -64%) after consumption of the unrefined carbohydrate diet relative to the simple carbohydrate diet [false discovery rate (FDR): all P < 0.05), whereas Anaerostipes abundance was higher (0.35% compared with 0.12%; FDR: P = 0.04) after the simple carbohydrate diet relative to the refined carbohydrate diet. Metatranscriptomics indicated upregulation of 2 cellular stress genes (FDR: P < 0.1) after the unrefined carbohydrate diet compared with the simple carbohydrate or refined carbohydrate diets. The microbial expression of 3 cellular/oxidative stress and immune response genes was higher (FDR: P < 0.1) after the simple carbohydrate diet relative to the refined carbohydrate diet. No significant diet effect was observed in fecal SCFA concentrations. Independent of diet, we observed 16 associations (all FDR: P < 0.1) of taxon abundance (15 phylum and 1 genera) with serum inflammatory markers and also with fecal SCFA and SBA concentrations. Conclusions: Consuming an unrefined carbohydrate-rich diet had a modest effect on the gut microbiome and SBAs, resulting in favorable associations with selected CMRFs. Simple carbohydrate-and refined carbohydrate-rich diets have distinctive effects on the gut microbiome, suggesting differential mechanisms mediate their effects on cardiometabolic health. This trial was registered at clinicaltrials.gov as NCT01610661.