Bifidobacterium bifidum Strain BB1 Inhibits Tumor Necrosis Factor-α–Induced Increase in Intestinal Epithelial Tight Junction Permeability via Toll-Like Receptor-2/Toll-Like Receptor-6 Receptor Complex–Dependent Stimulation of Peroxisome Proliferator-Activated Receptor γ and Suppression of NF-κB p65

Raz Abdulqadir, Rana Al-Sadi, Mohammad Haque, Yash Gupta, Manmeet Rawat, Thomas Y. Ma

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Bifidobacterium bifidum strain BB1 causes a strain-specific enhancement in intestinal epithelial tight junction (TJ) barrier. Tumor necrosis factor (TNF)-α induces an increase in intestinal epithelial TJ permeability and promotes intestinal inflammation. The major purpose of this study was to delineate the protective effect of BB1 against the TNF-α–induced increase in intestinal TJ permeability and to unravel the intracellular mechanisms involved. TNF-α produces an increase in intestinal epithelial TJ permeability in Caco-2 monolayers and in mice. Herein, the addition of BB1 inhibited the TNF-α increase in Caco-2 intestinal TJ permeability and mouse intestinal permeability in a strain-specific manner. BB1 inhibited the TNF-α–induced increase in intestinal TJ permeability by interfering with TNF-α–induced enterocyte NF-κB p50/p65 and myosin light chain kinase (MLCK) gene activation. The BB1 protective effect against the TNF-α–induced increase in intestinal permeability was mediated by toll-like receptor-2/toll-like receptor-6 heterodimer complex activation of peroxisome proliferator-activated receptor γ (PPAR-γ) and PPAR-γ pathway inhibition of TNF-α–induced inhibitory kappa B kinase α (IKK-α) activation, which, in turn, resulted in a step-wise inhibition of NF-κB p50/p65, MLCK gene, MLCK kinase activity, and MLCK-induced opening of the TJ barrier. In conclusion, these studies unraveled novel intracellular mechanisms of BB1 protection against the TNF-α–induced increase in intestinal TJ permeability. The current data show that BB1 protects against the TNF-α–induced increase in intestinal epithelial TJ permeability via a PPAR-γ–dependent inhibition of NF-κB p50/p65 and MLCK gene activation.

Original languageEnglish (US)
Pages (from-to)1664-1683
Number of pages20
JournalAmerican Journal of Pathology
Volume194
Issue number9
DOIs
StatePublished - Sep 2024

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Fingerprint

Dive into the research topics of 'Bifidobacterium bifidum Strain BB1 Inhibits Tumor Necrosis Factor-α–Induced Increase in Intestinal Epithelial Tight Junction Permeability via Toll-Like Receptor-2/Toll-Like Receptor-6 Receptor Complex–Dependent Stimulation of Peroxisome Proliferator-Activated Receptor γ and Suppression of NF-κB p65'. Together they form a unique fingerprint.

Cite this