# Host–gut microbiota interactions in health and disease: mechanisms and intervention strategies

## TL;DR

The gut microbiota interacts with the host to regulate health and disease through metabolites and immune functions, with potential for microbiota-based interventions.

## Contribution

This review highlights bidirectional regulatory mechanisms and challenges in microbiota-based interventions for disease management.

## Key findings

- Gut microbiota produces metabolites that regulate energy metabolism, immune homeostasis, and neural behavior.
- Dysbiosis contributes to diseases like diabetes, fatty liver, and inflammatory bowel disease through disrupted signaling and inflammation.
- Microbiota interventions face challenges due to individual variability and difficulties in long-term colonization.

## Abstract

The mammalian gut microbiota is a complex and dynamic “microbial organ” that interacts with its host. The gut microbiota contains a vast gene pool and metabolic capacity, producing key metabolites such as short-chain fatty acids (SCFAs), bile acids, vitamins, and other compounds. These metabolites regulate core physiological functions like energy metabolism, immune homeostasis, and neural behavior via the gut-brain axis (GBA), immune signaling networks, and other pathways. This review explores the bidirectional regulatory role of the gut microbiota. The gut microbiota influences the host’s metabolism and immune functions through its metabolites and structural components, while the host’s physiological state, internal environment, and lifestyle can alter the microbiota’s composition and function, creating a complex feedback network. Furthermore, the main mechanisms of dysbiosis in diseases are also explored. Dysregulation of the gut microbiota can damage the intestinal mucosal barrier, induce chronic inflammation, disrupt metabolic and immune signaling, and contribute to diseases such as type 2 diabetes, non-alcoholic fatty liver disease, inflammatory bowel disease, rheumatoid arthritis, and neurodegenerative disorders. Microbiota-based interventions, such as probiotics, prebiotics, and fecal microbiota transplantation (FMT), can be promising in disease management, but their clinical applications face challenges, including individual genetic backgrounds, lifestyles, and environmental factors, as well as difficulties in achieving long-term colonization of specific strains. Future research needs to uncover precise causal mechanisms in host-microbe interactions, as well as develop individualized microbiota intervention strategies to provide new theoretical bases and practical tools for the prevention, diagnosis, and treatment of major diseases.