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 (1x109 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-ß1). 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.

Effect of mesenchymal stem cells derived exosomes and green tea polyphenols on acetic acid induced ulcerative colitis in adult male albino rats.

Ulcerative colitis (UC) is one of the inflammatory bowel diseases (IBD) that result in recurrent inflammation plus ulcers of the colon and rectum. Recently, mesenchymal stem cell-derived exosomes MSC-EXs have shown a lot of promise for the treatment of gut disorders, with cell regeneration and angiogenesis. Green tea polyphenols (GTPs) display specific beneficial effects on health and pathologies. The aim of this study was to explore the possible effect of MSC-EXs and GTPs on acetic acid-induced UC in rats. Sixty adult male rats were divided into five groups: group I, control group; group II, UC; group ΙIΙ, UC treated with GTPs; group ΙV, UC treated with MSC-EXs; and group V, UC treated with combined GTPs and MSC-EXs. Colonic samples were processed for histological and immunohistochemical methods. Expression of CXCR2 and TLR4 levels was measured. Groups ΙI and III showed ulceration, loss of surface columnar epithelium, disturbed crypt architecture with few goblet cells, and many cellular infiltrations with the overexpression of CXCR2 and TLR4. Group IV showed attenuation of some histological changes. Group V showed improvement of the most histological and immunohistochemical changes described previously. MSC-EXs represent future therapeutic hopes for chronic intestinal inflammatory states, keeping the integrity of innate immunity through their regenerative and anti-inflammatory effects. The combination of GTPs and MSC-EXs was more effective and produced an additive effect than using MSC-EXs alone.