Maik Pietzner1, Kathrin Budde1, Malte Rühlemann2, Henry Völzke3, Georg Homuth4, Frank U Weiss5, Markus M Lerch5, Fabian Frost5. 1. Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany. 2. Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany. 3. Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany. 4. Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany. 5. Department of Medicine A, University Medicine Greifswald, Greifswald, Germany.
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.
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.
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