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

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.

The crosstalk between microbiota and metabolites in AP mice: an analysis based on metagenomics and untargeted metabolomics

“…In addition to the relationship between the oral microbiome and pancreatic function, alterations in pancreatic functions can directly affect the profile of the gut microbiome by inducing changes in metabolite production. Impaired exocrine pancreatic function is the most prominent host factor affecting the composition and diversity of the human intestinal microbiome ( Frost et al., 2019 ; Girdhar et al., 2022 ).…”

Nutritional therapy bridges the critical cut-off point for the closed-loop role of type 2 diabetes and bone homeostasis: A narrative review

“…The gut microbiota is a complex, dynamic, spatially heterogeneous ecosystem that collectively maintains the normal physiological dynamic balance of the human body. Animal studies using transplanted fecal microorganisms in germ-free mice have shown that gut microbiota play an important role in bone metabolism [ [112] , [113] , [114] ] and blood sugar regulation [ 115 , 116 ]. Additionally, the composition and abundance of healthy microbiota reflect the intestinal mucosal barrier effect, the production of major metabolites such as SCFAs, and the promotion of unbound secondary bile acid formation, which are common factors for alleviating T2DM and promoting bone health.…”

Exploring a novel therapeutic strategy: the interplay between gut microbiota and high-fat diet in the pathogenesis of metabolic disorders

“…Li et al added the commensal bacterium Alistipes onderdonkii to obese mice induced by HFD and found a reduction in hyperglycemia and alleviation of HFD-induced inflammation and glucose intolerance ( 143 ). Another study revealed that HFD could induce pancreatic acinar cell proliferation through gut microbiota, resulting in a 40% increase in pancreatic weight, alterations in pancreatic secretion, as reflected by decreased levels of GLP-1 and peptide YY, increased levels of glucose-dependent insulinotropic polypeptide, and changes in 32 host proteins within the gut, with pancreatic enzymes showing the most significant changes ( 214 ). Further research utilizing lipid-induced mice fed with HFD demonstrated that adding broccoli to the diet led to alterations in the diversity and structure of Proteobacteria, Akkermansia , and Mucispirillum schaedleri in the gut, improving insulin resistance ( 215 ).…”