摘要The use of next-generation probiotics(NGP)in pigs for combating diseases has been subject to limited research.Here we explored the potential of a well-known NGP candidate Akkermansia muciniphila tar-geting pig gut health.In the first screening experiment,we found that the abundance of A.muciniphila peaked at 14 d old but decreased at weaning(21 d old;P＜0.05),suggesting the weaning period may be an effective window for A.muciniphila intervention.Following that,48 crossbred weaned pigs at 28 d old were randomly assigned to five groups:control(CON),high/low live A.muciniphila(HA/LA),and high/low heat-killed A.muciniphila(HIA/LIA).From 1 to 28 d old,the CON group received gastric infusion of anaerobic sterile saline every other day;the HA and LA groups were gavaged every other day with 1 × 1010 CFU/5 mL and 5 × 108 CFU/5 mL live A.muciniphila,respectively;and the HIA and LIA groups were gavaged every other day with 1 × 1010 CFU/5 mL and 5 × 108 CFU/5 mL heat-killed A.muciniphila,respectively.At d 29,pigs in the CON group were randomly and equally divided into two groups,one of which was named the enterotoxigenic Escherichia coli(ETEC)group,and all groups except CON received a 5-d ETEC challenge.The supplementation of A.muciniphila numerically reduced the diarrhea rate of weaned pigs compared to the pigs that only received the ETEC challenge(P=0.57),but the LIA group had a higher diarrhea rate than the CON group(P＜0.05).Consistent with this,the supplementation of A.muciniphila improved the small intestinal morphology and structure,proportion of CD4+T lymphocytes in the blood,as well as the expression of genes related to intestinal barrier and antioxidant indices of pigs with ETEC challenge,especially for the LA group(P＜0.05).Meanwhile,A.muciniphila supplementation reduced the expression of ETEC virulence factor genes in the ileum and colon of pigs challenged by ETEC(P＜0.05).Therefore,A.muciniphila may protect the intestinal health of weaned piglets from damage caused by ETEC infection,but the effect may vary depending on the concentration and activity of A.muciniphila.