Commercial milk kefir exerts immunomodulatory TLR-mediated responses on in vitro models of the human intestinal epithelium

The human gut microbiota plays a critical role in maintaining health and homeostasis. Kefir, a traditional fermented beverage, is recognized for its health benefits, yet the underlying mechanisms remain incompletely understood. This study aimed to investigate the microbial composition, functional profiles, viability, and immunomodulatory properties of 11 commercial kefir beverages compared to 4 pharmaceutical probiotic formulations. Samples were analyzed both before and after in vitro gastrointestinal digestion, and their effects on intestinal immune signaling pathways, including Aryl Hydrocarbon Receptor (AhR), Toll-like Receptor 4 (TLR4), and Toll-like Receptor 9 (TLR9), were assessed. Our findings revealed high variability in kefir microbiomes, with significant differences in bacterial and fungal communities across samples. A negative correlation was found between fungal diversity, bacterial diversity, and immune receptor responses, suggesting that microbe-microbe interactions play a key role in kefir's immunomodulatory potential. Differences between kefirs and pharmaceutical probiotics, particularly in TLR9 modulation, highlight the distinct immunoregulatory effects of kefir. Future research should focus on strain-specific contributions, bioactive metabolites, long-term health effects of kefir consumption and synergic outcomes derived from milk matrix-microbial elements interactions. This study provides a foundation for further exploration into the therapeutic potential of fermented foods in promoting immune balance and gut homeostasis.