Exploring the synergistic potential of probiotics and vitamin D to ameliorate acute TNBS-induced colitis in mice

Abstract

Inflammatory Bowel Disease (IBD), either Crohn’s disease or Ulcerative Colitis, are diseases characterized by chronic inflammation of the gastrointestinal tract, disruption of mucosal barrier, gut dysbiosis and vitamin D deficiency. The use of probiotics or vitamin D supplements have been studied individually in different colitis models to determine their beneficial effects by increasing tight junction proteins such as occludin. However, the synergistic effects of combining these treatments to target tight junction expression are still unknown. Therefore, the objective of this research was to demonstrate the effcacy of probiotics and high dietary vitamin D to ameliorate colonic inflammation by increasing mucosal barrier integrity. We hypothesized that co-administration of a probiotic mixture with vitamin D would reduce colitis-induced inflammation by increasing tight junction expression. For the methodology, male and female C57BL/6 mice were divided into four treatment groups: Colitis+Vehicle (n=10), Colitis+Probiotic (n=10), Colitis+Vitamin D (n=11), Colitis+Probiotic+Vitamin D (n=7). Animals received seven days of pretreatment with Vivomixx probiotics in water, high vitamin D (5IU/g) in food, or both. On day 7, animals were anesthetized lightly, and colitis induction was done by intracolonic administration of 0.1mL of 4mg TNBS in 30% ethanol. Water, food, and body weight were monitored daily. Animals were sacrificed on day ten, the colonic tissue was removed and assessed for inflammation then stained for occludin expression by immunofluorescence, and probiotic colonization was confirmed within fecal samples by RT-PCR amplification of S. Thermophilus gene. Results indicate that all animals decreased weight after colitis induction, but only animals receiving probiotic had a slight recovery by day 10. Animals receiving the probiotic mixture had higher S. Thermophilus expression in fecal samples compared to vehicle (p<0.001) indicating appropriate colonization. A significant reduction in macroscopic damage score (3.92 vs. 7.42, p<0.05) and microscopic score (3.42 vs 7.20, p<0.01) was found in animals with Probiotic+Vitamin D compared to vehicle. Although an increase in occludin expression was observed with probiotic administration it did not reach statistical significance. In conclusion, findings indicate a beneficial effect of combining probiotics and vitamin D on colonic tissue damage in an animal model of acute colitis but this did not impact the tight junction protein occludin. This work was supported by RISE (R25GM082406), G-RISE (T32GM144896), PRI MD Summer Program and Porter Physiology Development Fellowship. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.