Age-related changes in intestinal immunity and the microbiome

J Leukoc Biol. 2021 Jun;109(6):1045-1061. doi: 10.1002/JLB.3RI0620-405RR. Epub 2020 Oct 5.


The gastrointestinal (GI) tract is a vitally important site for the adsorption of nutrients as well as the education of immune cells. Homeostasis of the gut is maintained by the interplay of the intestinal epithelium, immune cells, luminal Ags, and the intestinal microbiota. The well-being of the gut is intrinsically linked to the overall health of the host, and perturbations to this homeostasis can have severe impacts on local and systemic health. One factor that causes disruptions in gut homeostasis is age, and recent research has elucidated how critical systems within the gut are altered during the aging process. Intestinal stem cell proliferation, epithelial barrier function, the gut microbiota, and the composition of innate and adaptive immune responses are all altered in advanced age. The aging population continues to expand worldwide, a phenomenon referred to as the "Silver Tsunami," and every effort must be made to understand how best to prevent and treat age-related maladies. Here, recent research about changes observed in the intestinal epithelium, the intestinal immune system, the microbiota, and how the aging gut interacts with and influences other organs such as the liver, lung, and brain are reviewed. Better understanding of these age-related changes and their impact on multi-organ interactions will aid the development of therapies to increase the quality of life for all aged individuals.

Keywords: epithelium; inflammaging; inflammation; liver; lung; microbiome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Age Factors
  • Aging / immunology
  • Aging / metabolism
  • Animals
  • Gastrointestinal Microbiome / immunology*
  • Gastrointestinal Tract / physiology*
  • Homeostasis
  • Humans
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / microbiology*
  • Organ Specificity