Postbiotics from Lactobacillus helveticus Attenuate Enterotoxigenic Bacteroides fragilis-Induced Inflammation and NF-κB Activation in Colorectal Epithelial Cells.

Colorectal cancer (CRC), the third most common malignancy worldwide, arises from a complex interplay of genetic, environmental, and microbial factors. Enterotoxigenic Bacteroides fragilis (ETBF) promotes CRC progression by secreting metalloprotease toxins, such as fragilysin (B. fragilis toxin, BFT), which disrupt intestinal epithelial barrier integrity, activate proinflammatory pathways (e.g., NF-κB), and drive carcinogenesis. Conversely, probiotics such as Lactobacillus helveticus may help attenuate inflammation and tumorigenesis. This study assessed the anti-inflammatory effects of heat-killed L. helveticus and its cell-free supernatant (CFS) on ETBF-induced inflammation in Caco-2 human intestinal epithelial cells. Cells were exposed to purified BFT (1 ng/mL) to induce inflammation, then treated with heat-killed L. helveticus (0.5 mg/mL) or CFS (0.5 mg/mL) for 48 h. Gene expression of cytokines (IL-1β, IL-8, IL-10) and NF-κB was quantified via quantitative reverse transcription polymerase chain reaction (qRT-PCR). ETBF significantly upregulated NF-κB (4-fold; p = 0.0007) and induced morphological disruptions. Treatments upregulated anti-inflammatory IL-10 (2-fold and 5-fold, respectively; p = 0.002 each) and reduced proinflammatory IL-8 (p = 0.005 and p = 0.002), with no change in IL-1β (p > 0.05). Treated cells showed restored morphology, indicating reduced inflammation and cytotoxicity. These findings illustrate the potential of non-viable L. helveticus to modulate inflammation, possibly via NF-κB inhibition and postbiotic metabolites. Future research should investigate strain-specific mechanisms, in vivo efficacy, and expanded cytokine profiles to optimize interventions.