Gut Microbiota Regulate Pancreatic Growth, Exocrine Function and Gut Hormones

Khyati Girdhar, Marion Soto, Qian Huang, Lucie Orliaguet, Carly Cederquist, Bharathi Sundaresh, Jiang Hu, Maximilian Figura, Amol Raisingani, Emanuel E Canfora, Ercument Dirice, Shiho Fujisaka, Gijs H Goossens, Ellen E Blaak, Rohit N Kulkarni, C Ronald Kahn, Emrah Altindis*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Growing evidence indicates an important link between gut microbiota, obesity, and metabolic syndrome. Alterations in exocrine pancreatic function are also widely present in patients with diabetes and obesity. To examine this interaction, C57BL/6J mice were fed either a chow diet, high-fat diet (HFD) or HFD plus oral vancomycin or metronidazole to modify the gut microbiome. HFD alone leads to a 40% increase in pancreas weight, decreased glucagon-like peptide-1 and peptide YY levels, and increased glucose-dependent insulinotropic peptide in the plasma. Quantitative proteomics identified 138 host proteins in fecal samples of these mice, of which 32 were significantly changed by HFD. The most significant of these were the pancreatic enzymes. These changes in amylase and elastase were reversed by antibiotic treatment. These alterations could be reproduced by transferring gut microbiota from donor C57BL/6J mice to germ-free. By contrast, antibiotics had no effect on pancreatic size or exocrine function in C57BL/6J mice fed a chow diet. Further, one week vancomycin administration significantly increased amylase and elastase levels in obese prediabetic men. Thus, the alterations in gut microbiota in obesity can alter pancreatic growth, exocrine function and gut endocrine function, and may contribute to the alterations observed in patients with obesity and diabetes.

Original languageEnglish
Pages (from-to)945-960
Number of pages16
JournalDiabetes
Volume71
Issue number5
Early online date25 Feb 2022
DOIs
Publication statusPublished - 2022

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