UC Davis

Fermented dairy products have emerged as promising functional foods for improving gastrointestinal (GI) health, yet the mechanisms underlying the benefits of fermented dairy products are not yet known. This dissertation aimed to review the current evidence on fermented dairy and GI health (Chapter 1) and investigate the capacity of probiotic-fermented milk to mitigate inflammation and improve barrier function using a mouse model for inflammatory bowel disease (Chapter 2) and in vitro using the Caco-2 cell line (Chapter 3). The review of human clinical trials assessed the effects of fermented dairy consumption on gut symptoms and biomarkers of gut health, which included inflammatory markers, barrier integrity, short-chain fatty acid levels, and microbiota composition (Chapter 1). In general, fermented dairy intake resulted in modest improvements in some GI symptoms, with fermented milk containing probiotic strains demonstrating the most promise in improving gut health. However, there was no consistent trend in how fermented dairy products altered the gut microbiota composition. The outcomes varied substantially depending on the fermented dairy product and probiotic strain. Since many products contained added probiotics, this highlighted the need to delineate the dairy matrix versus probiotic effects. To investigate this in my dissertation, I used a mouse model of dextran sodium sulfate (DSS)-induced colitis (Chapter 2). My findings showed sex-dependent differences in DSS-induced colitis progression and recovery, with worse outcomes in females, and these effects may have been due to differences in their intestinal microbiota. Feeding mice milk fermented by Lacticaseibacillus casei BL23 improved weight recovery, specifically among females. Milk supported better weight retention among males, while BL23-milk enhanced colonic ion transport. To determine how milk and probiotics can directly modulate the intestinal epithelium, the capacity of fermented milk to mitigate the effects of the inflammatory cytokine, IFNγ, on intestinal epithelial cells (IECs) was assessed (Chapter 3). A cell-free preparation of milk fermented by L. casei BL23 or L. casei ATCC334, but not regular milk, mitigated inflammatory disruption of the intestinal epithelial barrier. It was shown that this occurred via epidermal growth factor receptor activation in intestinal epithelial cells. Transcriptomic analysis of the IECs revealed that milk fermented by either L. casei BL23 or ATCC334 increased the expression of the gene encoding for the tight junction protein claudin-2. Both fermented milks also reversed inflammation-induced suppression of sterol metabolism, potentially through the master regulator of cholesterol synthesis and uptake known as sterol regulatory element-binding protein 2 (SREBP2). Higher sterol gene expression correlated with milder colitis in DSS-treated mice, implicating sterol regulation in L. casei-mediated barrier effects. In summary, this dissertation significantly expands the understanding of the benefits of fermented dairy and probiotic consumption on gut health. The findings also underscore the intricate interactions between diet, microbiota, host factors, and intracellular pathways governing GI responses to inflammation. This work further provides molecular insights into the impact of probiotic-fermented dairy on gut health.