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

Mol Nutr Food Res. 2024 Aug;68(16):e2400295. doi: 10.1002/mnfr.202400295. Epub 2024 Jul 21.

Abstract

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-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.

Keywords: immunomodulatory cytokines; probiotics; rat diarrhea; tannic acid; tight junction proteins.

MeSH terms

  • Animals
  • Cytokines* / metabolism
  • Diarrhea* / drug therapy
  • Disease Models, Animal*
  • Ileum / drug effects
  • Ileum / metabolism
  • Intestinal Mucosa* / drug effects
  • Intestinal Mucosa* / metabolism
  • Lacticaseibacillus rhamnosus* / physiology
  • Male
  • Polyphenols
  • Probiotics / pharmacology
  • Proliferating Cell Nuclear Antigen / metabolism
  • Rats
  • Rats, Wistar*
  • Tannins* / pharmacology
  • Zonula Occludens-1 Protein / genetics
  • Zonula Occludens-1 Protein / metabolism

Substances

  • Tannins
  • Cytokines
  • Zonula Occludens-1 Protein
  • Proliferating Cell Nuclear Antigen
  • tannic acid
  • Polyphenols