TY - JOUR

T1 - Rewiring host–microbe interactions and barrier function during gastrointestinal inflammation

AU - Jensen, Sune K

AU - Pærregaard, Simone I

AU - Brandum, Emma P

AU - Jørgensen, Astrid S

AU - Hjortø, Gertrud M

AU - Jensen, Benjamin A H

PY - 2022/1/25

Y1 - 2022/1/25

N2 - Organismal survival depends on a well-balanced immune system and maintenance of host–microbe mutualism. The fine-tuned relationship between the gut microbiota and host immunity is constantly challenged by opportunistic bacteria testing the integrity of gastrointestinal (GI) barrier defenses. Barrier dysfunction reduces immunological tolerance towards otherwise innocuous microbes; it is a process that may instigate chronic inflammation. Paradoxically, sustained inflammation further diminishes barrier function, enabling bacterial translocation to extra-intestinal tissues. Once translocated, these bacteria stimulate systemic inflammation, thereby compromising organ function. While genetic risk alleles associate with barrier dysfunction, environmental stressors are key triggers of GI inflammation and associated breakdown in immune tolerance towards resident gut microbes. As dietary components dictate substrate availability, they also orchestrate microbiota composition and function, including migratory and pro-inflammatory potential, thus holding the capacity to fuel both GI and extra-intestinal inflammation. Additionally, Western diet consumption may weaken barrier defenses via curbed Paneth cell function and diminished host-defense peptide secretion. This review focuses on intervenable niches of host–microbe interactions and mucosal immunity with the ambition to provide a framework of plausible strategies to improve barrier function and regain tolerance in the inflamed mucosa via nutritional intervention.

AB - Organismal survival depends on a well-balanced immune system and maintenance of host–microbe mutualism. The fine-tuned relationship between the gut microbiota and host immunity is constantly challenged by opportunistic bacteria testing the integrity of gastrointestinal (GI) barrier defenses. Barrier dysfunction reduces immunological tolerance towards otherwise innocuous microbes; it is a process that may instigate chronic inflammation. Paradoxically, sustained inflammation further diminishes barrier function, enabling bacterial translocation to extra-intestinal tissues. Once translocated, these bacteria stimulate systemic inflammation, thereby compromising organ function. While genetic risk alleles associate with barrier dysfunction, environmental stressors are key triggers of GI inflammation and associated breakdown in immune tolerance towards resident gut microbes. As dietary components dictate substrate availability, they also orchestrate microbiota composition and function, including migratory and pro-inflammatory potential, thus holding the capacity to fuel both GI and extra-intestinal inflammation. Additionally, Western diet consumption may weaken barrier defenses via curbed Paneth cell function and diminished host-defense peptide secretion. This review focuses on intervenable niches of host–microbe interactions and mucosal immunity with the ambition to provide a framework of plausible strategies to improve barrier function and regain tolerance in the inflamed mucosa via nutritional intervention.

UR - https://doi.org/10.1093/gastro/goac008

U2 - 10.1093/gastro/goac008

DO - 10.1093/gastro/goac008

M3 - Journal article

C2 - 35291443

VL - 10

SP - 1

EP - 15

JO - Gastroenterology Report

JF - Gastroenterology Report

SN - 2052-0034

M1 - goac008

ER -