Inulin Fermentable Fiber Ameliorates Type I Diabetes via IL22 and Short-Chain Fatty Acids in Experimental Models

Cell Mol Gastroenterol Hepatol. 2021;12(3):983-1000. doi: 10.1016/j.jcmgh.2021.04.014. Epub 2021 Apr 30.

Abstract

Background & aims: Nourishment of gut microbiota via consumption of fermentable fiber promotes gut health and guards against metabolic syndrome. In contrast, how dietary fiber impacts type 1 diabetes is less clear.

Methods: To examine impact of dietary fibers on development of type 1 diabetes in the streptozotocin (STZ)-induced and spontaneous non-obese diabetes (NOD) models, mice were fed grain-based chow (GBC) or compositionally defined diets enriched with a fermentable fiber (inulin) or an insoluble fiber (cellulose). Spontaneous (NOD mice) or STZ-induced (wild-type mice) diabetes was monitored.

Results: Relative to GBC, low-fiber diets exacerbated STZ-induced diabetes, whereas diets enriched with inulin, but not cellulose, strongly protected against or treated it. Inulin's restoration of glycemic control prevented loss of adipose depots, while reducing food and water consumption. Inulin normalized pancreatic function and markedly enhanced insulin sensitivity. Such amelioration of diabetes was associated with alterations in gut microbiota composition and was eliminated by antibiotic administration. Pharmacologic blockade of fermentation reduced inulin's beneficial impact on glycemic control, indicating a role for short-chain fatty acids (SCFA). Furthermore, inulin's microbiota-dependent anti-diabetic effect associated with SCFA-independent restoration of interleukin 22, which was necessary and sufficient to ameliorate STZ-induced diabetes. Inulin-enriched diets significantly delayed diabetes in NOD mice.

Conclusions: Fermentable fiber confers microbiota-dependent increases in SCFA and interleukin 22 that, together, may have potential to prevent and/or treat type 1 diabetes.

Keywords: Cellulose; Gut Microbiota; Insulin Resistance; Inulin; Type 1 Diabetes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bacteria / classification*
  • Bacteria / drug effects
  • Bacteria / genetics
  • Bacteria / isolation & purification
  • Diabetes Mellitus, Type 1 / chemically induced
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / microbiology
  • Dietary Fiber / administration & dosage*
  • Dietary Fiber / pharmacology
  • Disease Models, Animal
  • Fatty Acids, Volatile / metabolism*
  • Gastrointestinal Microbiome / drug effects
  • Glycated Hemoglobin / metabolism
  • Interleukin-22
  • Interleukins / metabolism*
  • Inulin / administration & dosage*
  • Inulin / pharmacology
  • Male
  • Mice
  • Mice, Inbred NOD
  • Organ Size / drug effects
  • Pancreas / drug effects
  • Pancreas / physiopathology
  • Streptozocin / adverse effects
  • Treatment Outcome

Substances

  • Dietary Fiber
  • Fatty Acids, Volatile
  • Glycated Hemoglobin A
  • Interleukins
  • hemoglobin A1c protein, human
  • Streptozocin
  • Inulin