Gut Microbiota Regulate Pancreatic Growth, Exocrine Function, and Gut Hormones

Authors

Khyati Girdhar, Biology Department Boston College, Chestnut Hill, MA.
Marion Soto, Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA.
Qian Huang, Biology Department Boston College, Chestnut Hill, MA.
Lucie Orliaguet, Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA.
Carly Cederquist, Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA.
Bharathi Sundaresh, Biology Department Boston College, Chestnut Hill, MA.
Jiang Hu, Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA.
Maximilian Figura, Biology Department Boston College, Chestnut Hill, MA.
Amol Raisingani, Biology Department Boston College, Chestnut Hill, MA.
Emanuel E. Canfora, Department of Human Biology, Maastricht University, Maastricht, the Netherlands.
Ercument Dirice, Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA.Follow
Shiho Fujisaka, Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA.
Gijs H. Goossens, Department of Human Biology, Maastricht University, Maastricht, the Netherlands.
Ellen E. Blaak, Department of Human Biology, Maastricht University, Maastricht, the Netherlands.
Rohit N. Kulkarni, Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA.
C Ronald Kahn, Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA.
Emrah Altindis, Biology Department Boston College, Chestnut Hill, MA.

Author Type(s)

Faculty

DOI

10.2337/db21-0382

Journal Title

Diabetes

First Page

945

Last Page

960

Document Type

Article

Publication Date

5-1-2022

Department

Pharmacology

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 a chow diet, a high-fat diet (HFD), or an 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 the 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 mice. By contrast, antibiotics had no effect on pancreatic size or exocrine function in C57BL/6J mice fed the chow diet. Further, 1 week vancomycin administration significantly increased amylase and elastase levels in obese men with prediabetes. 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.

Recommended Citation

Girdhar, K., Soto, M., Huang, Q., Orliaguet, L., Cederquist, C., Sundaresh, B., Hu, J., Figura, M., Raisingani, A., Canfora, E. E., Dirice, E., Fujisaka, S., Goossens, G. H., Blaak, E. E., Kulkarni, R. N., Kahn, C. R., & Altindis, E. (2022). Gut Microbiota Regulate Pancreatic Growth, Exocrine Function, and Gut Hormones. Diabetes, 71 (5), 945-960. https://doi.org/10.2337/db21-0382