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Gut Microbiota Regulate Pancreatic Growth, Exocrine Function and Gut Hormones

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posted on 25.02.2022, 15:41 authored by 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
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.

Funding

DRC P30 DK036836 G. Harold & Leila Y. Mathers Foundation MF-1905-00311 NIH R01DK031026 R01DK033201 R01DK067536 NIH NIDDK 1K01DK117967-01 TI

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