(P27-033-24) Predicting Human Fecal and Plasma Short-Chain Fatty Acids Using Diet, Microbiome, and Inflammation Markers

Objectives: Gut microbes produce short-chain fatty acids (SCFAs), which are associated with broad health benefits, including improved gut barrier integrity, decreased risk of cancer and type 2 diabetes, and reduced inflammation. Despite widespread interest in SCFAs, it is not fully known how diet and/or the gut microbiome could be modulated to improve SCFA production. Therefore, the objective of the current study is to determine the dietary and microbial predictors of fecal and plasma SCFAs in healthy U.S. adults.

Methods: We measured the fecal and plasma SCFAs from 330 healthy men and women, age 18-65 y, BMI 17-43 kg/m², who participated in the cross-sectional, observational USDA Nutritional Phenotyping Study. Dietary intake was assessed in the 7-10 days prior to fecal/plasma collection via three ASA24 recalls (recent diet) and an FFQ (habitual diet). Using partial correlation and random forests, we investigated the ability of diet, microbiome (WGS), and inflammation biomarkers to predict the abundance of SCFAs.

Results: We first tested the hypothesis that diet quality, fiber abundance, or fiber diversity impact SCFA abundance. We found that a higher Healthy Eating Index for habitual diet was associated with more fecal butyrate than expected (r = 0.18, p = 0.015). We detected no difference in SCFA abundance between individuals with or without frank gut or systemic inflammation (fecal calprotectin >= 100µg/g, plasma C-reactive protein >= 10 mg/L). TaxaHFE-selected dietary and microbiome features weakly predicted fecal, but not plasma SCFAs. Inflammation markers were poor predictors apart from the inverse association of fecal MPO with plasma propionate. The top diet and microbiome predictors of fecal butyrate included potatoes and the thiamine biosynthesis pathway, respectively.

Conclusions: These findings illustrate the complex biology underpinning SCFA production in the gut. For example, thiamine is a critical cofactor and resistant starch a substrate for microbial butyrate production. Both thiamine biosynthesis gene abundance and potato consumption positively correlated with fecal butyrate, suggesting potatoes may promote butyrate-producing microbes. Our findings also demonstrate the ability of hierarchical feature engineering and machine learning to identify diet and microbiome predictors.

Funding Sources: Oak Ridge Institute for Science and Education