< em > Clostridium scindens < /em > exacerbates experimental necrotizing enterocolitis via upregulation of the apical sodium dependent bile acid transporter

Am J Physiol Gastrointest Liver Physiol. 2023 Nov 7. doi: 10.1152/ajpgi.00102.2023. Online ahead of print.ABSTRACTNecrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in premature infants. Evidence indicates that bile acid homeostasis is disrupted during NEC: ileal bile acid levels are elevated in animals with experimental NEC, as is expression of the apical sodium dependent bile acid transporter (Asbt). In addition, bile acids-which are synthesized in the liver-are extensively modified by the gut microbiome, including via conversion of primary bile acids to more cytotoxic secondary forms. We hypothesized that the addition of bile acid modifying bacteria would increase susceptibility to NEC in a neonatal rat model of the disease. The secondary bile acid producing species Clostridium scindens exacerbated both incidence and severity of NEC. C. scindens upregulated the bile acid transporter Asbt and increased levels of intra-enterocyte bile acids. Treatment with C. scindens also altered bile acids profiles and increased hydrophobicity of the ileal intracellular bile acid pool. The ability of C. scindens to enhance NEC requires bile acids, as pharmacological sequestration of ileal bile acids protects animals from developing disease. These findings indicate that bile acid modifying bacteria can contribute to NEC pathology and provides additional evidence for the role of bile acids in the pathophysiology of experimental NEC.PMID:37933481 | DOI:10.1152/ajpgi...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - Category: Physiology Authors: Source Type: research