The Gut–Immune Axis: How Gut Health Influences Autoimmune Disease

In autoimmune conditions, we know there is a strong and well-established connection between the gut and the immune system. This relationship is often referred to as the gut–immune axis.

The microbiome lives throughout our digestive tract and continuously sends signals to the immune system based on what we eat and what enters the body. When potentially harmful substances enter the gut, such as pathogens, toxins, or irritants, the microbiome and gut immune cells generate “danger signals” that activate immune responses. The gut microbiome also helps protect us by competing with harmful bacteria and maintaining the integrity of the gut lining.

A large portion of the immune system is located in and around the gut, where it is in constant communication with the gut microbiome. Specialized immune tissues (gut-associated lymphoid tissue or GALT) serve as training grounds for immune cells, helping determine what should be tolerated and what should trigger a response.

When the diet does not adequately support the gut microbiome, particularly when it is low in fiber and plant foods that promote short-chain fatty acid production or high in processed foods, the microbial balance can begin to shift. You can think of the microbiome like a city, if the food supply changes or becomes inadequate, the population and structure of the city begin to change as well. Some organisms may thrive while others decline, leading to an overall imbalance.

As this imbalance develops, the function of the intestinal lining can also be affected. Normally, the cells lining the digestive tract are tightly joined together and carefully regulate what is allowed to pass from the gut into the bloodstream. When gut integrity is compromised, these tight junctions can become more permeable, allowing larger or inappropriate particles to cross into the circulation. This process is sometimes referred to as increased intestinal permeability. Eventually, increased intestinal permeability can lead to leaky gut.

When particles that are not meant to be in the bloodstream enter circulation, such as fragments of bacteria or incompletely digested food proteins, the immune system may recognize them as threats. In response, it produces inflammatory signals and antibodies in an attempt to neutralize and control these substances.

In some cases, antibodies formed against foreign particles may cross-react with human tissues, a process known as molecular mimicry. This occurs when parts of a foreign protein resemble structures found in the body. While certain dietary proteins (such as gluten) have stronger evidence for molecular mimicry in autoimmune conditions, other foods may provoke immune reactions primarily through immune activation and inflammation, rather than directly targeting a specific organ. Immune reactions to dietary proteins may increase overall immune activation, which can worsen existing autoimmune activity.

Overall, the gut and immune system influence one another in both directions. The immune system shapes the gut microbiome, and the microbiome plays a critical role in educating and regulating immune responses. Because of this close relationship, addressing gut health is often a valuable starting point in autoimmune care. Supporting the gut environment, improving digestion, and reducing inflammatory triggers can help lower excessive immune signaling and create conditions that allow the immune system to become more regulated.

References

1. Frontiers article on gut-immune axis (2025)
   Guo, X., Wang, K., Liu, Q., Baran, N., & Ma, W. (2025). The gut-immune axis in primary immune thrombocytopenia (ITP): A paradigm shifts in treatment approaches. Frontiers in Immunology, 16. https://doi.org/10.3389/fimmu.2025.1595977

2. Frontiers article on gut microbiota and autoimmune disease (2024)
   Emerging role of gut microbiota in autoimmune diseases. (2024). Frontiers in Immunology. https://doi.org/10.3389/fimmu.2024.1365554

3. PMC article on gut-thyroid axis (Hashimoto’s)
   Zhao, F., Feng, J., Li, J., Zhao, L., Liu, Y., Chen, H., & Jin, Y. (2024). Intestinal microbiota regulates the gut-thyroid axis: The new dawn of improving Hashimoto thyroiditis. Frontiers in Endocrinology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10884059/

4. PMC article on microbiota influence on thyroid function
   Knezevic, J., Starchl, C., Tmava Berisha, A., & Amrein, K. (2020). Thyroid-Gut-Axis: How does the microbiota influence thyroid function? Nutrients, 12(6), 1769. https://doi.org/10.3390/nu12061769