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Profiling of the human intestinal microbiome and bile acids under physiologic conditions using an ingestible sampling device

ABSTRACT: The spatiotemporal structure of the human microbiome, proteome, and metabolome reflects and determines regional intestinal physiology and may have implications for disease. Yet, we know little about the distribution of microbes, their environment, and their biochemical activity in the gut because of reliance on stool samples and limited access to only some regions of the gut using endoscopy in fasting or sedated individuals. To address these deficiencies, we developed and evaluated a safe, ingestible device that collects samples from multiple regions of the human intestinal tract during normal digestion and maintains the viability of microbes from these locations. The collection of 240 intestinal samples from 15 healthy individuals using the device and subsequent multi-omics analyses revealed significant differences between microbes, phages, host proteins, and metabolites present in the intestines versus stool. Certain microbial taxa and gene classes were differentially enriched, and prophage induction was more prevalent in the intestines than in stool. The host proteome and bile acid profiles varied along the intestines and were highly distinct from those of stool. Correlations between gradients in bile acid concentrations and microbial abundancepredicted species that altered the bile acid pool through deconjugation. Furthermore,microbially conjugated bile acids displayed amino acid-dependent trends in concentration that were not apparent in stool. Overall, non-invasive longitudinal profilingof microbes, proteins, and bile acids along the intestinal tract under physiological conditions can help elucidate the roles of the gut microbiome and metabolome in humanphysiology and disease.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Intestinal Juice

SUBMITTER: Mario Oroshi

LAB HEAD: Matthias Mann

PROVIDER: PXD038906 | Pride | 2023-01-18

REPOSITORIES: Pride

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Project description:There is increased interest in the potential protective role of dietary Ca in the development of metabolic disorders related to the metabolic syndrome. Ca-induced intestinal precipitation of fatty acids and bile acids as well as systemic metabolic effects of Ca on adipose tissue is proposed to play a causal role. In this experiment, we have studied all these aspects to validate the suggested protective effect of Ca supplementation, independent of other dietary changes, on the development of diet-induced obesity and insulin resistance. In our diet intervention study, C57BL/6J mice were fed high-fat diets differing in Ca concentrations (50 v. 150 mmol/kg). Faecal excretion analyses showed an elevated precipitation of intestinal fatty acids (2·3-fold; P < 0·01) and bile acids (2-fold; P < 0·01) on the high-Ca diet. However, this only led to a slight reduction in fat absorption (from 98 to 95 %; P < 0·01), mainly in the distal small intestine as indicated by gene expression changes. We found no effect on body-weight gain. Lipolysis and lipogenesis-related parameters in adipose tissue also showed no significant changes on the high-Ca diet, indicating no systemic effects of dietary Ca on adiposity. Furthermore, early gene expression changes of intestinal signaling molecules predicted no protective effect of dietary Ca on the development of insulin resistance, which was confirmed by equal values for insulin sensitivity on both diets. Taken together, our data do not support the proposed protective effect of dietary Ca on the development of obesity and/or insulin resistance, despite a significant increase in fecal excretion of fatty acids and bile acids. Keywords: Diet intervention study Nine-week-old mice were fed a high fat purified diet with a low calcium concentration of 50mmol/kg (LCa diet) or a high calcium concentration of 150mmol/kg (HCa diet) for 8 weeks. Body weight was recorded weekly and after 7 weeks of diet intervention an oral glucose tolerance test was performed. For microarray analysis, after 2 weeks of diet intervention, 6 mice per diet group were anaesthetized with a mixture of isofluorane (1.5%), nitrous oxide (70%) and oxygen (30%) and the small intestines were excised. Adhering fat and pancreatic tissue were carefully removed. The small intestines were divided in three equal parts along the proximal to distal axis (SI 1, SI 2 and SI 3) and microarray analysis was performed on pooled mucosal scrapings.

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Profiling of the human intestinal microbiome and bile acids under physiologic conditions using an ingestible sampling device

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