Abstract
BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer-related deaths, significantly disrupting enteric neurotransmission within the colon. While the effects of CRC on the enteric nervous system (ENS) of the colon are well documented, its impact on the small intestine remains underexplored. This study aims to investigate the influence of colorectal carcinogenesis on the small intestine's ENS and evaluate the individual neuroprotective effects of microencapsulated quercetin and Bifidobacterium animalis. METHODS: Wistar rats were subjected to chemically induced colorectal carcinogenesis, followed by 14 weeks of treatment with microencapsulated quercetin and B. animalis. Gastrointestinal transit times were assessed, and colonic and jejunal samples underwent histopathological and immunohistochemical analyses to evaluate neuronal markers (HuC/D, nNOS, VIP). Cholinergic neurons were not directly assessed. RESULTS: Aberrant crypt foci confirmed the effectiveness of the colorectal carcinogenesis induction model. The mean gastric emptying time (MGET) was notably shorter in the B. animalis-treated group. Colorectal carcinogenesis significantly reduced the density and size of HuC/D+ neurons in the myenteric and submucosal plexuses of the jejunum. Treatments with either microencapsulated quercetin or B. animalis significantly enhanced neuronal density and size in the jejunum and improved nitrergic neuronal density (nNOS-IR). Additionally, VIPergic neuron density increased in the submucosal plexus, and varicosity size increased in the myenteric plexus in the CR group; treatments reduced this varicosity size. CONCLUSION: This study provides the first evidence that colorectal carcinogenesis damages jejunal neurons. Treatments with microencapsulated quercetin or B. animalis independently preserved neuronal density and modulated gastrointestinal function. However, their combined administration did not enhance these effects, highlighting the need for further research into therapeutic interventions for preserving ENS integrity during colorectal carcinogenesis.