Gut-Centric Multi-System Regulation by Bacillus subtilis and Bacillus natto: A Review of Their Probiotic Functions in Nutrition, Immunity, and Metabolism

BACKGROUND: (BN) exhibited superior metabolic capacity and stress resistance and are more suitable for industrial applications. However, limited understanding of their nutritional and intestinal health mechanisms has constrained their food potential. OBJECTIVES: This review systematically expounded on the 'triple mechanism' of BS and BN and their effects on intestinal nutrition, immunity and metabolism benefit for the first time. METHODS: We searched PubMed, Scopus, Web of Science, and Google Scholar for studies on livestock, model organisms, and human research from 2000 to 2025. After evaluating relevance and eligibility, 115 articles were included. RESULTS: Firstly, by secreting various digestive enzymes, BS and BN directly enhanced the small intestine digestive and absorptive efficiency and promoted animal growth. In particular, BN significantly increases calcium absorption in postmenopausal women. Secondly, as the antigen carrier that induced intestinal mucosal immunity, BS and BN enhanced the host's defense ability by strengthening the expression of tight junction proteins, mucins, and inflammatory factors and bidirectionally regulated constipation and acute diarrhea in the human body. Thirdly, they reshaped the structure of the intestinal microbiota and their metabolic profile in the form of the gut-liver/gut-adipose axis, including enriching beneficial bacteria, activating lipid metabolism pathways such as PI3K/AKT and AMPK/SREBP, and regulating liver targets such as PPAR and CD36, thereby reducing insulin resistance and liver injury and maintaining overall metabolic homeostasis. CONCLUSIONS: mediated their probiotic benefits through a gut-centric, multi-system regulatory strategy, involving nutrient utilization, immune homeostasis, and microbial-host metabolic interactions. This integrated mechanism provided a robust foundation for their targeted application in functional formulations and fermented food science.