Immunology and the Microbiome

The human body, inside and out, is covered in microbes, with the bulk of them lining the intestinal walls. Recent research is examining the relationship between microbes and the body and the ways in which this relationship impacts the immune system. Even though this research is still in the early stages, some researchers and clinicians believe that the microbiome could become a cornerstone of autoimmune disease treatment.1

Microbiota are implicated in almost every chronic condition, including autoimmune conditions. Imbalance among the gut microbiota may drive inflammatory conditions such as obesity, diabetes, inflammatory bowel disease, colorectal cancer, and immunosenescence in the elderly,2 as well as endocrine diseases.3 The accumulation of microbes that are perceived as pathogens in the microbiome likely contributes to the inflammatory cascade that impacts immune function and tolerance.4

This research points to the potential for treatment and prevention of autoimmune conditions using therapies directed at the microbiome. A recent review article described the exciting number of studies focused on the microbiome, therapeutic probiotics, and autoimmune conditions including systemic lupus erythematosus (SLE), type 1 diabetes, and more.5 Even central nervous system autoimmune conditions may benefit from treating the microbiome and modulating its activity.6

In one surprising study, researchers found that bacteria in the small intestines of mice and humans can travel to other organs, where they may trigger an autoimmune response.7 The researchers also found that this autoimmune reaction can be suppressed with antibiotic treatment or vaccines designed to target the bacteria. These findings offer a new understanding of, and exciting promise for, the treatment of autoimmune conditions such as SLE and autoimmune liver disease.7

“How are microbes in our gut acting as potential triggers for autoimmune diseases like rheumatoid arthritis?” asks IFM educator Robert Rountree, MD. In the following video, he talks about emerging research connecting the microbiome and its genetic expressions to human health and wellness.

IFM educator Robert Rountree, MD, has provided his unique combination of traditional family medicine, nutrition, herbology, and mind-body therapy in Boulder, CO, since 1983. He is a diplomate of the American Board of Holistic Medicine.

The gut microbiota can exert immunomodulatory effects,8 particularly through antigen-specific T cells9 and their related anti- and pro-inflammatory cytokines, as well as several other mediators of inflammation.3 Infections and dysbiosis can affect immunologic tolerance in autoimmunity via mechanisms including bystander activation, molecular mimicry, epitope spreading, polyclonal activation of B cells and T cells, and auto-inflammatory activation of the innate immune system.10

Some recent research shows that probiotic treatments may impact the immune system by influencing the activity of cells in the gut. One study found that a four-strain probiotic is capable of modifying the immune response in vitro by enhancing colonic butyrate production in cells from healthy humans;11 the production of anti-inflammatory cytokines (IL-6 and IL-10) was increased and the production of inflammatory chemokines (MCP-1, CXCL 10, and IL-8) was reduced. While this research was conducted in vitro, the results suggest that probiotic species alone may not result in a clinical effect on their own; rather, bacteria interact with and alter metabolic and immune byproducts.11

There is great potential that a better understanding of the interactions between the microbiome and the immune system may lead to new ways of treating and preventing autoimmune dysfunction. Functional Medicine’s Immune Advanced Practice Module provides the latest research and clinical insights into the microbiome and autoimmunity as well as how to successfully assess and treat other types of immune dysfunction.

Learn More About Immune Imbalance

Looking for further information about the role of the microbiome in immune-related diseases? Read more.

What are the effects of the microbiome on cardiovascular health? Learn more.


  1. Proal AD, Albert PJ, Marshall TG. The human microbiome and autoimmunity. Curr Opin Rheumatol. 2013;25(2):234-240. doi:1097/BOR.0b013e32835cedbf
  2. Peterson CT, Sharma V, Elmén L, Peterson SN. Immune homeostasis, dysbiosis and therapeutic modulation of the gut microbiota. Clin Exp Immunol. 2015;179(3):363-377. doi:1111/cei.12474
  3. Cianci R, Pagliari D, Piccirillo CA, Fritz JH, Gambassi G. The microbiota and immune system crosstalk in health and disease. Mediators Inflamm. 2018;2018:2912539. doi:1155/2018/2912539
  4. Proal AD, Marshall TG. Re-framing the theory of autoimmunity in the era of the microbiome: persistent pathogens, autoantibodies, and molecular mimicry. Discov Med. 2018;25(140):299-308.
  5. de Oliveira GLV, Leite AZ, Higuchi BS, Gonzaga MI, Mariano VS. Intestinal dysbiosis and probiotic applications in autoimmune diseases. Immunology. 2017;152(1):1-12. doi:1111/imm.12765
  6. Colpitts SL, Kasper LH. Influence of the gut microbiome on autoimmunity in the central nervous system. J Immunol. 2017;198(2):596-604. doi:4049/jimmunol.1601438
  7. Manfredo Vieira S, Hiltensperger M, Kumar V, et al. Translocation of a gut pathobiont drives autoimmunity in mice and humans. Science. 2018;359(6380):1156-1161. doi:1126/science.aar7201
  8. Chen B, Sun L, Zhang X. Integration of microbiome and epigenome to decipher the pathogenesis of autoimmune diseases. J Autoimmun. 2017;83:31-42. doi:1016/j.jaut.2017.03.009
  9. Alexander KL, Targan SR, Elson CO 3rd. Microbiota activation and regulation of innate and adaptive immunity. Immunol Rev. 2014;260(1):206-220. doi:1111/imr.12180
  10. Ruff WE, Kriegel MA. Autoimmune host-microbiota interactions at barrier sites and beyond. Trends Mol Med. 2015;21(4):233-244. doi:1016/j.molmed.2015.02.006
  11. Moens F, Van den Abbeele P, Basit AW, et al. A four-strain probiotic exerts positive immunomodulatory effects by enhancing colonic butyrate production in vitro. Int J Pharm. 2019;555:1-10. doi:1016/j.ijpharm.2018.11.020

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