Strain-dependent efficacy of pasteurized Akkermansia muciniphila in alleviating colitis reveals AKK2645 restores immune and microbial homeostasis

Ulcerative colitis (UC) is a chronic inflammatory disease caused by intestinal immune dysregulation and microbial imbalance. Pasteurized Akkermansia muciniphila has attracted significant attention in recent research due to its anti-inflammatory properties and favorable safety profile. In this study, 39 strains of pasteurized A. muciniphila with anti-inflammatory properties were preliminarily screened using an in vitro HT-29 cell inflammation model. Subsequently, the in vivo efficacy of these strains was evaluated in DSS-induced UC mouse models. It is noteworthy that the 39 strains exhibited considerable variation in their efficacy in treating UC. Among them, pasteurized AKK2645 demonstrated the strongest therapeutic efficacy in both in vitro and in vivo . Pasteurized AKK2645 altered the ratio of Th17/Treg and Th1/Th2 cells in the colon, thereby reducing the mRNA expression of pro-inflammatory cytokines such as il-6 , il-1β , tnf-α , il-17a , ifn-γ , and il-23 , while simultaneously upregulating the mRNA expression of anti-inflammatory cytokines such as il-10 , foxp3 , and gata3 . Furthermore, 16S rRNA analysis revealed that pasteurized AKK2645 reshaped the gut microbiota composition by increasing the abundance of beneficial bacterial genera such as Dubosiella , Bifidobacterium , and Limosilactobacillus , while simultaneously reducing the abundance of potentially pathogenic genera such as Ileibacterium and Alistipes . This study provides novel evidence that A. muciniphila inactivation exerts strain-specific effects on inflammation regulation. Furthermore, it indicates that pasteurized AKK2645 exerts a beneficial effect on colitis by modulating immune cell populations and microbial homeostasis.