Exocrine Pancreatic Function Modulates Plasma Metabolites Through Changes in Gut Microbiota Composition

J Clin Endocrinol Metab. 2021 Apr 23;106(5):e2290-e2298. doi: 10.1210/clinem/dgaa961.

Abstract

Purpose: Exocrine pancreatic function is critically involved in regulating the gut microbiota composition. At the same time, its impairment acutely affects human metabolism. How these 2 roles are connected is unknown. We studied how the exocrine pancreas contributes to metabolism via modulation of gut microbiota.

Design: Fecal samples were collected in 2226 participants of the population-based Study of Health in Pomerania (SHIP/SHIP-TREND) to determine exocrine pancreatic function (pancreatic elastase enzyme-linked immunosorbent assay) and intestinal microbiota profiles (16S ribosomal ribonucleic acid gene sequencing). Plasma metabolite levels were determined by mass spectrometry.

Results: Exocrine pancreatic function was associated with changes in the abundance of 28 taxa and, simultaneously, with those of 16 plasma metabolites. Mediation pathway analysis revealed that a significant component of how exocrine pancreatic function affects the blood metabolome is mediated via gut microbiota abundance changes, most prominently, circulating serotonin and lysophosphatidylcholines.

Conclusion: These results imply that the effect of exocrine pancreatic function on intestinal microbiota composition alters the availability of microbial-derived metabolites in the blood and thus directly contributes to the host metabolic changes associated with exocrine pancreatic dysfunction.

Keywords: 16S rDNA; metabolome; microbiome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blood Chemical Analysis
  • Blood Proteins / metabolism
  • Cohort Studies
  • Female
  • Gastrointestinal Microbiome / genetics
  • Gastrointestinal Microbiome / physiology*
  • Germany
  • Humans
  • Male
  • Metabolome*
  • Middle Aged
  • Pancreas, Exocrine / physiology*
  • RNA, Ribosomal, 16S / analysis
  • RNA, Ribosomal, 16S / genetics

Substances

  • Blood Proteins
  • RNA, Ribosomal, 16S