Search

Most processing of the human diet occurs in the small intestine. Metabolites in the small intestine originate from host secretions, plus the ingested exposome1 and microbial transformations. Here we probe the spatiotemporal variation of upper intestinal luminal contents during routine daily digestion in 15 healthy male and female participants. For this, we use a non-invasive, ingestible sampling device to collect and analyse 274 intestinal samples and 60 corresponding stool homogenates by combining five mass spectrometry assays2,3 and 16S rRNA sequencing. We identify 1,909 metabolites, including sulfonolipids and fatty acid esters of hydroxy fatty acids (FAHFA) lipids. We observe that stool and intestinal metabolomes differ dramatically. Food metabolites display trends in dietary biomarkers, unexpected increases in dicarboxylic acids along the intestinal tract and a positive association between luminal keto acids and fruit intake. Diet-derived and microbially linked metabolites account for the largest inter-individual differences. Notably, two individuals who had taken antibiotics within 6 months before sampling show large variation in levels of bioactive FAHFAs and sulfonolipids and other microbially related metabolites. From inter-individual variation, we identify Blautia species as a candidate to be involved in FAHFA metabolism. In conclusion, non-invasive, in vivo sampling of the human small intestine and ascending colon under physiological conditions reveals links between diet, host and microbial metabolism.

Most utilization of human diets occurs in the small intestine, which remains largely unstudied. Here, we used a novel non-invasive, ingestible sampling device to probe the spatiotemporal variation of upper intestinal luminal contents during routine daily digestion in 15 healthy subjects. We analyzed 274 intestinal samples and 60 corresponding stool homogenates by combining five metabolomics assays and 16S rRNA sequencing. We identified 1,909 metabolites, including sulfonolipids and novel bile acids. Stool and intestinal metabolomes differed dramatically. Food metabolites displayed known differences and trends in dietary biomarkers, unexpected increases in dicarboxylic acids along the intestinal tract, and a positive association between luminal keto acids and fruit intake. Diet-derived and microbially linked metabolites accounted for the largest inter-subject differences. Interestingly, subjects exhibited large variation in levels of bioactive fatty acid esters of hydroxy fatty acids (FAHFAs) and sulfonolipids. Two subjects who had taken antibiotics within 6 months prior to sampling showed markedly different patterns in these and other microbially related metabolites; from this variation, we identified Blautia species as most likely to be involved in FAHFA metabolism. Thus, in vivo sampling of the human small intestine under physiologic conditions can reveal links between diet, host and microbial metabolism.

BackgroundWe hypothesized that drinking water, sanitation, handwashing (WSH), and nutritional interventions would improve environmental enteric dysfunction (EED), a potential contributor to stunting.MethodsWithin a subsample of a cluster-randomized, controlled trial in rural Bangladesh, we enrolled pregnant women in 4 arms: control, WSH, child nutrition counseling plus lipid-based nutrient supplements (N), and nutrition plus WSH (N+WSH). Among the birth cohort, we measured biomarkers of gut inflammation (myeloperoxidase, neopterin), permeability (alpha-1-antitrypsin, lactulose, mannitol), and repair (regenerating gene 1β) at median ages 3, 14, and 28 months. Analysis was intention-to-treat.ResultsWe assessed 1512 children. At age 3 months, compared to controls, neopterin was reduced by nutrition (-0.21 log nmol/L; 95% confidence interval [CI], -.37, -.05) and N+WSH (-0.20 log nmol/L; 95% CI, -.34, -.06) interventions; similar reductions were observed at 14 months. At 3 months, all interventions reduced lactulose and mannitol (-0.60 to -0.69 log mmol/L). At 28 months, myeloperoxidase was elevated in the WSH and nutrition arms (0.23-0.27 log ng/mL) and lactulose was higher in the WSH arm (0.30 log mmol/L; 95% CI, .07, .53).ConclusionsReductions in permeability and inflammation at ages 3 and 14 months suggest that the interventions promoted healthy intestinal maturation; however, by 28 months, the WSH and nutrition arms showed elevated EED biomarkers. These results underscore the importance of developing a better understanding of EED pathophysiology and targeting interventions early in childhood, when they are likely to have the largest benefit to intestinal health.Clinical trials registrationNCT01590095.