Clostridium butyricum and Clostridium tyrobutyricum: angel or devil for necrotizing enterocolitis?

ABSTRACT Necrotizing enterocolitis (NEC) is a challenging gastrointestinal disease that disproportionately affects premature neonates, with high incidence and case-fatality rates. Despite extensive research efforts, the pathogenesis and mechanisms of NEC remain unclear, making it difficult to effectively eradicate. However, it has been established that dysbiosis of gut microbes occurs before the onset of NEC, providing compelling evidence for the potential use of probiotic therapy. As such, we have focused our attention on two probiotics in particular: Clostridium butyricum and Clostridium tyrobutyricum, especially in light of recent breakthroughs that have linked several Clostridia species with NEC. To determine whether C. butyricum and C. tyrobutyricum are pathogenic or probiotic, we conducted a comparison of the phenotypic traits of NEC mice treated with each bacterium. Our results confirm that treatment with C. tyrobutyricum restores intestinal barrier integrity and alleviates inflammatory immune responses associated with NEC. In contrast, treatment with C. butyricum exacerbates intestinal barrier damage and promotes immune disorder, including increased numbers of macrophages, monocytes, and neutrophils in the intestinal lamina propria. Further analysis of the gut microbiome suggests that the positive effects of C. tyrobutyricum treatment are associated with an increase in Akkermansia muciniphila, while C. butyricum treatment decreases the level of A. muciniphila, which accounts for its negative effect on NEC. This study sheds light on the fact that treatment with C. tyrobutyricum, but not C. butyricum, has the potential to protect against NEC development. The opposite effects of these two probiotics on NEC may result from their different modulation of the level of A. muciniphila, a gut microbe that is closely associated with intestinal homeostasis. In summary, by improving the abundance of A. muciniphila to alleviate intestinal inflammation and enhance intestinal barrier integrity, supplementation with C. tyrobutyricum may become a promising therapy for NEC. IMPORTANCE This study sheds light on that treatment with Clostridium tyrobutyricum but not Clostridium butyricum is entitled to protect against necrotizing enterocolitis (NEC) development potentially. The mechanisms behind the opposite effect on NEC may result in different modulation on the level of Akkermansia 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. This study sheds light on that treatment with Clostridium tyrobutyricum but not Clostridium butyricum is entitled to protect against necrotizing enterocolitis (NEC) development potentially. The mechanisms behind the opposite effect on NEC may result in different modulation on the level of Akkermansia 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.