IL-1β knockout increases the intestinal abundancy of Akkermansia muciniphila

Benef Microbes. 2023 Sep 1;14(4):361-370. doi: 10.1163/18762891-20220042.

Abstract

The proinflammatory cytokine interleukin-1β (IL-1β) is known to be upregulated in patients suffering from metabolic syndrome. IL-1β contributes to insulin resistance in obesity and type 2 diabetes, yet its influence on the intestinal microbiome is incompletely understood. The data presented here demonstrate that mice genetically deficient in IL-1β show a specific alteration of intestinal colonisation of a small group of bacteria. Especially Akkermansia muciniphila, a bacterium reported to be inversely associated with obesity, diabetes, cardiometabolic diseases and low-grade inflammation, showed increased colonisation in IL-1β knockout mice. In comparative microarray analysis from mucus scrapings of the colon mucosa of IL-1β knockout and wildtype mice, angiogenin 4 mRNA was strongly reduced in IL-1β knockout animals. Since the presence of angiogenin 4 in the culture medium showed a significant growth inhibition on A. muciniphila which was not detectable for other bacteria tested, IL-1β induced expression of angiogenin 4 is a strong candidate to be responsible for the IL-1β induced suppression of A. muciniphila colonisation. Thus, the data presented here indicate that IL-1β might be the lacking link between inflammation and suppression of A. muciniphila abundance as observed in a variety of chronic inflammatory disorders.

MeSH terms

  • Akkermansia* / genetics
  • Animals
  • Colon / microbiology
  • Gastrointestinal Microbiome*
  • Interleukin-1beta* / genetics
  • Interleukin-1beta* / metabolism
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Ribonuclease, Pancreatic / genetics
  • Ribonuclease, Pancreatic / metabolism

Substances

  • Ang4 protein, mouse
  • Interleukin-1beta
  • Ribonuclease, Pancreatic
  • IL1B protein, mouse

Supplementary concepts

  • Akkermansia muciniphila