Xuan Shi, Yiping Li, Yi Cheng, Weichi Liu, Zelong Li, Hao Jin, Lai‐Yu Kwok, Zhihong Sun
Lactic acid bacteria (LAB) are essential in both food fermentation and host health maintenance. This review synthesizes their roles, from traditional applications in fermented foods to their emerging importance in health management through gut microbiota modulation. We first highlight LAB diversity and functions in fermentation, emphasizing the potential for resource development informed by genomic analysis. Their ecological interactions along the food-gut axis are examined, with a focus on their influence on gastrointestinal function and systemic health. Mechanistic insights are provided on how LAB promote gut homeostasis, supported by in vivo evidence demonstrating their ability to enhance intestinal health and mitigate extra-intestinal disorders via regulation of multiple gut-organ axes. The biomedical potential of engineered LAB is also discussed, including applications in immunomodulation, anti-inflammatory responses, antimicrobial activity, therapeutic protein production, and vaccine delivery. Finally, we outline future directions, emphasizing the need for advanced screening strategies, standardized evaluation systems, and integration of emerging biotechnologies to fully harness LAB's clinical and industrial potential. Overall, this review underscores the dual role of LAB as key agents in traditional dietary practices and as promising tools for innovative therapeutic interventions in food science and human health.