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

2026-02-28
Nutrients 18(5)

PubMed: 41829972
DOI: 10.3390/nu18050802

Study Design

Type: Systematic Review
Population: studies on livestock, model organisms, and human research from 2000 to 2025
Methods: 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. 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.

Rigorous Journal

Background

Compared with lactic acid-producing probiotics, spore-producing probiotics such as Bacillus subtilis (BS) and Bacillus natto (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

Bacillus subtilis and Bacillus natto 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.

Research Insights

Supplement	Dose	Health Outcome	Effect Type	Effect Size	Source
Bacillus subtilis	—	Improved Bowel Function	Beneficial	Moderate	View source bidirectionally regulated constipation and acute diarrhea in the human body.
Bacillus subtilis	—	Improved Calcium Absorption	Beneficial	Moderate	View source BN significantly increases calcium absorption in postmenopausal women.
Bacillus subtilis	—	Improved Digestive Efficiency	Beneficial	Moderate	View source by secreting various digestive enzymes, BS and BN directly enhanced the small intestine digestive and absorptive efficiency and promoted animal growth.
Bacillus subtilis	—	Improved Insulin Resistance	Beneficial	Moderate	View source thereby reducing insulin resistance and liver injury and maintaining overall metabolic homeostasis.
Bacillus subtilis	—	Improved Intestinal Barrier Function	Beneficial	Moderate	View source BS and BN enhanced the host's defense ability by strengthening the expression of tight junction proteins, mucins, and inflammatory factors
Bacillus subtilis	—	Improved Metabolic Homeostasis	Beneficial	Moderate	View source maintaining overall metabolic homeostasis.
Bacillus subtilis	—	Reduced Liver Injury	Beneficial	Moderate	View source thereby reducing insulin resistance and liver injury and maintaining overall metabolic homeostasis.