The Microbiota Protects against Ischemia/Reperfusion-Induced Intestinal Injury through Nucleotide-Binding Oligomerization Domain-Containing Protein 2 (NOD2) Signaling

摘要: Nucleotide-binding oligomerization domain-containing protein 2 (NOD2), an intracellular pattern recognition receptor, induces autophagy on detection of muramyl dipeptide (MDP), a component microbial cell walls. The role bacteria and NOD2 signaling toward ischemia/reperfusion (I/R)–induced intestinal injury response is unknown. Herein, we report that I/R-induced in germ-free (GF) C57BL/6 wild-type (WT) mice worse than conventionally derived mice. More important, microbiota-mediated protection against abrogated Nod2−/− GF Also, WT raised specific pathogen-free (SPF) conditions fared better SPF Moreover, i.p. administered 10 mg/kg MDP were protected compared with the inactive enantiomer, l-MDP, effect lost However, administration failed to protect from control, phenomenon correlating undetectable Nod2 mRNA level epithelium autophagy-inducer rapamycin increased levels LC3+ puncta injured tissue These findings demonstrate protects I/R promotes wound healing, likely through induction response.