Alleviating Clostridium perfringens-Induced Gut Lesionsin Broiler Chickens by Orally Administered Bovine Intestinal Alkaline Phosphatase

Intestinal alkaline phosphatase (AP) detoxifies lipopolysaccharides, which has been exploited in treating infection of Gram-negative bacterial pathogens such as Escherichia coli. Orally administered AP has the potential to modulate the gut microbiota, which is in part ascribed to its ability to degrade ATP, a well-known inhibitor of gut commensal bacteria. In addition, AP can fortify the gut barrier. Therefore, we hypothesized that the enzyme might also be used to control intestinal Gram-positive pathogens such as Clostridium perfringens. Herein, broiler chickens were challenged with 3 × 10⁸ colony-forming units of C. perfringens daily from 14 to 20 days. Low (1000 U/kg of feed) and high (5000 U/kg of feed) doses of a recombinant bovine intestinal AP (bIAP) were orally administered to the chickens throughout the study. bIAP could indeedalleviate the gut lesion and diarrhea symptom in chickens challenged with C. perfringens and reversed the decline in their growth performance. 16S rRNA gene sequencing and non-targeted metabolomics analyses revealed that bIAP could modulate the gut microbiota, which was accompanied with a change of the gut metabolites profile, the improved intestinal integrity and immunity, and an ultimate protection of the animals from C. perfingens infection. Strikingly, the RT-qPCR assay showed that the transcript levels of key tight junction proteins zonula occludens-1, Mucin 2, claudin-1, and occludin in the duodenum, jejunum, and ileum were even superior in the high dose group than those in the unchallenged group, suggestive of enhanced integrity of the intestinal barrier. Enzymes such as bIAP are, therefore, a powerful tool in modulating the gut microbiota for better health of the host animals.