Lactobacillus rhamnosus GG and Tannic Acid Synergistically Promote the Gut Barrier Integrity in a Rat Model of Experimental Diarrhea via Selective Immunomodulatory Cytokine Targeting

Scope Diarrhea is a common health issue that contributes to a significant annual death rate among children and the elderly worldwide. The anti‐diarrheal activity of Lactobacillus rhamnosus GG (LGG) and tannic acid (TA), alone or combined, is examined, in addition to their effect on intestinal barrier integrity. Methods and results Fifty‐six adult male Wistar rats are randomly assigned into seven groups: control, LGG alone, TA alone, diarrhea model, diarrhea+LGG, diarrhea+TA, and diarrhea+LGG+TA‐treated groups. Diarrhea is induced by high‐lactose diet (HLD) consumption. LGG (1x10 9 CFU/rat) and TA (100 mg Kg −1 d −1 ) were given orally 4 days after HLD feeding and continued for 10 days. Ileum specimens are processed for biochemical analysis of the local intestinal cytokines, polymerase chain reaction (PCR), and histological study. Also, immunohistochemistry‐based identification of Proliferating Cell Nuclear Antigen (PCNA) and zonula occludens 1 (ZO‐1) is performed. Compared to the diarrhea model group, both treatments maintain the intestinal mucosal structure and proliferative activity and preserve ZO‐1 expression, with the combination group showing the maximal effect. However, LGG‐treated diarrheic rats show a remarkable decrease in the intestinal tissue concentrations of tumor necrosis factor‐alpha (TNF‐α) and nuclear factor Kappa beta (NF‐κB); meanwhile, TA treatment leads to a selective decrease of interferon‐gamma (INF‐γ) and transforming growth factor‐beta (TGF‐β1). Conclusion Individual LGG and TA treatments significantly alleviate diarrhea, probably through a selective immunomodulatory cytokine‐dependent mechanism, while the combination of both synergistically maintains the intestinal mucosa by keeping the intestinal epithelial barrier function and regenerative capability.