Naturally Immune For Life

Microbiota Plays  Critical Role in Immune Disorders

by Mary Ferrari

Introduction

The gut microbiota has been studied for decades and conclusive evidence shows that it influences the development, homeostasis and function of the immune system.

The Gut Microbiota and Immune System Function

The gut microbiota interacts to T cells or signals via Toll-like receptors and Nod-like receptors. These signals mediate cell induction and function, thus ensuring homeostasis in the human immune system.

Different types of bacteria in the gut help guide how T cells grow and develop. These include helper T cells (like Th1, Th2, and Th17) and regulatory T cells (Treg), which help control the immune system. Gut bacteria also make small substances called short-chain fatty acids (SCFAs). These help turn T cells on or off and keep the immune system balanced.

Evidence in Animal Models

Studies in germ-free mice (mice without gut bacteria) show how important this is. These mice have fewer Treg cells, no Th17 cells, and an imbalance in other T cells, leaning too much toward a Th2 response. When certain bacteria are added back, their immune system shifts and becomes more balanced again.

New research using advanced tools has also shown that mice with a more natural mix of bacteria (like wild mice) have immune systems that act more like humans compared to standard lab mice.

Overall, these findings show that gut bacteria play a big role in shaping the immune system. Changes in these bacteria are linked to diseases where the immune system does not work properly.

Microbiota and Immune Dysregulation

Gut microbiota dysbiosis is caused by a variety of mechanisms including improper infant gut development from formula feeding, microbiome imbalance, immune dysregulation, proinflammatory mechanisms, and metabolic activities.

Dysbiosis leads to various T cell-related diseases, including:

• rheumatoid arthritis (RA)
• type 1 and type 2 diabetes,
• asthma
• cardiovascular disease
• inflammatory bowel disease (IBD)
• cancer
• liver disease
• psychiatric disorders 

Current Research Limitations

Despite the importance of understanding microbiome-T cell interactions, most immunology experiments have been performed with limited microbiome composition such as specific pathogen free (SPF) or germ free (GF) mice. Experimental results using gnotobiotic, that is specific colonized mouse models in the drug development stage cannot fully represent humans. To address these limitations, a fecal microbiota transplant (FMT) mouse model with a gut microbiota similar to that of humans was developed using human or wild mouse feces. The FMT mouse model has an abundant and more diverse gut microbiome than current experimental animal models. Mice implanted with the wild mouse or human microbiota not only exhibit different degrees of microbial diversity but their systemic immunity is also affected.

Conclusion

Significant advances have been made in immunology and microbiology using microbiota and germ-free animals and next-generation sequencing. Many such studies have revealed the correlation between gut microbiota and the immune system. Research shows the role of gut microbiome in activating T cells and the development and promotion of autoimmune diseases and various cancers. FMT mouse models of Human and wild mice are expected to increase the success rate of preclinical studies. This will make it possible to overcome the limitations of using GF or SPF mice and will open new avenues for disease treatment and prevention based on the distribution of the gut microbiome.s