Faculty Collaboration Database

Dermal injury drives a skin to gut axis that disrupts the intestinal microbiome and intestinal immune homeostasis in mice. Nat Commun 2024 Apr 08;15(1):3009

Date

04/09/2024

Pubmed ID

38589392

Pubmed Central ID

PMC11001995

DOI

10.1038/s41467-024-47072-3

Scopus ID

2-s2.0-85189779985 (requires institutional sign-in at Scopus site)   80 Citations

Abstract

The composition of the microbial community in the intestine may influence the functions of distant organs such as the brain, lung, and skin. These microbes can promote disease or have beneficial functions, leading to the hypothesis that microbes in the gut explain the co-occurrence of intestinal and skin diseases. Here, we show that the reverse can occur, and that skin directly alters the gut microbiome. Disruption of the dermis by skin wounding or the digestion of dermal hyaluronan results in increased expression in the colon of the host defense genes Reg3 and Muc2, and skin wounding changes the composition and behavior of intestinal bacteria. Enhanced expression Reg3 and Muc2 is induced in vitro by exposure to hyaluronan released by these skin interventions. The change in the colon microbiome after skin wounding is functionally important as these bacteria penetrate the intestinal epithelium and enhance colitis from dextran sodium sulfate (DSS) as seen by the ability to rescue skin associated DSS colitis with oral antibiotics, in germ-free mice, and fecal microbiome transplantation to unwounded mice from mice with skin wounds. These observations provide direct evidence of a skin-gut axis by demonstrating that damage to the skin disrupts homeostasis in intestinal host defense and alters the gut microbiome.

Author List

Dokoshi T, Chen Y, Cavagnero KJ, Rahman G, Hakim D, Brinton S, Schwarz H, Brown EA, O'Neill A, Nakamura Y, Li F, Salzman NH, Knight R, Gallo RL

Author

Nita H. Salzman PhD, MD Center Director in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Colitis
Colon
Dextran Sulfate
Disease Models, Animal
Fecal Microbiota Transplantation
Gastrointestinal Microbiome
Hyaluronic Acid
Intestinal Mucosa
Mice
Mice, Inbred C57BL