Inulin prebiotic ameliorates type 1 diabetes dictating regulatory T cell homing via CCR4 to pancreatic islets and butyrogenic gut microbiota in murine model

J Leukoc Biol. 2024 Feb 23;115(3):483-496. doi: 10.1093/jleuko/qiad132.

Abstract

Gut dysbiosis is linked to type 1 diabetes mellitus (T1D). Inulin (INU), a prebiotic, modulates the gut microbiota, promoting beneficial bacteria that produce essential short-chain fatty acids for immune regulation. However, how INU affects T1D remains uncertain. Using a streptozotocin-induced (STZ) mouse model, we studied INU's protective effects. Remarkably, STZ + INU mice resisted T1D, with none developing the disease. They had lower blood glucose, reduced pancreatic inflammation, and normalized serum insulin compared with STZ + SD mice. STZ + INU mice also had enhanced mucus production, abundant Bifidobacterium, Clostridium cluster IV, Akkermansia muciniphila, and increased fecal butyrate. In cecal lymph nodes, we observed fewer CD4+Foxp3+ regulatory T cells expressing CCR4 and more Foxp3+CCR4+ cells in pancreatic islets, with higher CCL17 expression. This phenotype was absent in CCR4-deficient mice on INU. INU supplementation effectively protects against experimental T1D by recruiting CCR4+ regulatory T cells via CCL17 into the pancreas and altering the butyrate-producing microbiota.

Keywords: Treg; gut microbiota; immunoregulation; inulin; prebiotic; regulatory T cells; type 1 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Butyrates / pharmacology
  • Diabetes Mellitus, Type 1*
  • Disease Models, Animal
  • Forkhead Transcription Factors
  • Gastrointestinal Microbiome*
  • Inulin / pharmacology
  • Islets of Langerhans*
  • Mice
  • Prebiotics
  • T-Lymphocytes, Regulatory

Substances

  • Inulin
  • Prebiotics
  • Butyrates
  • Forkhead Transcription Factors