Gut-derived IL-13 contributes to growth via promoting hepatic IGF-1 production

Microbiome. 2024 Nov 23;12(1):248. doi: 10.1186/s40168-024-01929-3.

Abstract

Background: The gut microbiota has a profound effect on immunity and metabolic status of the host, which has increasingly attracted research communities. However, the intrinsic mechanism underlying the interplay among these three aspects remains unclear.

Results: Different immune states were established via shaping the population structure of gut microbiota with antibacterial agents. The gut microbiota population structures altered with the subtherapeutic level of antibacterial agents facilitated growth phenotype in both piglets and infant mice. Notably, increased colonization of Prevotella copri was observed in the intestinal microbiota, which shifted the immune balance from a CD4+ T cell-dominated population toward a T helper 2 cell (Th2) phenotype, accompanied by a significant elevation of interleukin-13 (IL-13) levels in the portal vein, which was found to display a strong positive correlation with hepatic insulin-like growth factor-1 (IGF-1) levels. Subsequent investigations unveiled that gut-derived IL-13 stimulated the production of hepatic IGF-1 by activating the IL-13R/Jak2/Stat6 pathway in vitro. The IGF-1 levels were increased in the muscles, leading to an upregulation of and resulted the increased genes associated with related to myofibrillar synthesis and differentiation, which ultimately improving the growth phenotype.

Conclusions: Our findings highlight the modification of gut immunity states as a central strategy for increasing anabolism of the host, which has significant implications for addressing human undernutrition/stunting, sarcopenia, obesity and related comorbidities. Video Abstract.

Keywords: Prevotella copri; Gut microbiota; IGF-1; IL-13; Immunity.

MeSH terms

  • Animals
  • Gastrointestinal Microbiome*
  • Humans
  • Insulin-Like Growth Factor I* / metabolism
  • Interleukin-13* / metabolism
  • Janus Kinase 2 / metabolism
  • Liver* / metabolism
  • Male
  • Mice
  • Prevotella / growth & development
  • STAT6 Transcription Factor / metabolism
  • Signal Transduction
  • Swine
  • Th2 Cells / immunology

Substances

  • Insulin-Like Growth Factor I
  • Interleukin-13
  • STAT6 Transcription Factor
  • Janus Kinase 2
  • insulin-like growth factor-1, mouse
  • Stat6 protein, mouse