Abstract Background Necrotizing enterocolitis (NEC), high incidence and case-fatality rate among premature neonates, is a frustrating gastrointestinal disease which hard to eradicate currently for its unclear pathogenesis and mechanisms. What has been conformed is that the gut microbes dysbiosis happens before the occurrence of NEC, providing robust evidence for the usage of probiotic therapy. Hence, we mainly concentrated on two probiotics: Clostridium butyricum and Clostridium tyrobutyricum especially after the breakthrough in discovering that several clostridia species have associations with NEC. Result To verify whether these two clostridia are pathogenic or probiotic, we compared the phenotypic traits of NEC mice treated with two clostridia. Our results proof that treatment with C. tyrobutyricum recovers the intestinal barrier integrity and alleviates inflammatory immune response of NEC, while treatment with C. butyricum aggrevates the intestinal barrier damage and promotes immune disorder including the number of macrophages, monocytes and neutrophils in Intestinal lamina propria. Further analysis of gut micrbiome implies that the positive effect of C. tyrobutyricum treatment is in association with the increase of Akkermansia muciniphila. Meanwhile, C. butyricum treatment decreases the level of A. muciniphila, which accounts for the negative effect to NEC. Conclusion This study sheds light on that treatment with C. tyrobutyricum but not C. butyricum is entitled to protect against NEC development potentially. The mechanisms behind the opposite effect on NEC may result in different modulation on the level of A. muciniphila, which is deeply associated with intestinal homoeostasis. Briefly, through improving the abundance of A. muciniphila to alleviate intestinal inflammation and enhance intestinal barrier integrity, C. tyrobutyricum supplement may become a promising therapy for NEC.

Clostridium butyricumandClostridium tyrobutyricum: angle or devil for Necrotizing enterocolitis?