insights

Immunology, the Microbiome, and Therapeutic Probiotics

The human body, inside and out, is covered in microbes, with the vast majority lining the intestinal walls. Ongoing research seeks to understand the relationship between host and microbiota, and how microbiota affect the human immune system. The underlying mechanisms of autoimmune regulation by the microbiota are just beginning to emerge, but some scientists believe that microbiota could become a cornerstone of autoimmune disease treatment.1

Microbiota are implicated in almost every chronic condition, including autoimmunity. Imbalance of gut microbiota and the immune system may drive inflammatory conditions such as obesity, diabetes (types I and II), inflammatory bowel disease, colorectal cancer, and immunosenescence in the elderly,2 as well as infectious and endocrine diseases.3 The accumulation of pathogens in the microbiome and gut likely contributes to the inflammatory cascade that changes immune function and tolerance.4 Even central nervous system autoimmune conditions benefit from treating the microbiome and modulating its activity.5

A recent review article described the exciting number of studies focused on the microbiome, therapeutic probiotics, and autoimmune conditions like systemic lupus erythematosus (SLE), type 1 diabetes, multiple sclerosis, and more.6 This area of research may contribute to understanding why some autoimmune conditions (like SLE) are increasing.7

In a groundbreaking study, a team of researchers found that bacteria in the small intestines of mice and humans can travel to other organs, where they trigger an autoimmune response.8 The team 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 lupus and autoimmune liver disease.8

“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 is the principal interface with the environment; dietary and environmental triggers primarily interact with the body through the mucosal membranes. Across 200 square meters of mucosal surface area and via 70% of all the lymphoid tissue in the body, the gut microbiota interacts with antigens to modulate the immune system.9 Microbiota exert immunomodulatory effects,10 particularly through antigen-specific T cells11 and their related anti- and pro-inflammatory cytokines, as well as several other mediators of inflammation.3

Commensal-specific T-regs can switch from regulatory to effector phenotypes during dysbiotic changes such as infection.12 This illustrates that 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.13

Another interesting piece of research, published in the International Journal of Pharmaceutics, demonstrates that a four-strain probiotic is capable of modifying the immune response in vitro by enhancing colonic butyrate production in cells from healthy humans.14 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. The results indicate that a probiotic species alone does not result in a clinical effect; rather, bacteria interact with and alter metabolic and immune byproducts.14

“If we can make a healthy microbiome healthier, the potential to improve conditions of dysbiosis is incredibly exciting,” said Simon Gaisford, professor of pharmaceutics at University College, London, in a press release.

Read more about the role of the microbiome in immune-related diseases

Learn more about the effects of the microbiome on cardiovascular health

References

  1. Proal AD, Albert PJ, Marshall TG. The human microbiome and autoimmunity. Curr Opin Rheumatol. 2013;25(2):234-240. doi:10.1097/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:10.1111/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:10.1155/2018/2912539.
  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. Colpitts SL, Kasper LH. Influence of the gut microbiome on autoimmunity in the central nervous system. J Immunol. 2017;198(2):596-604. doi:10.4049/jimmunol.1601438.
  6. 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:10.1111/imm.12765.  
  7. Rosser EC, Mauri C. A clinical update on the significance of the gut microbiota in systemic autoimmunity. J Autoimmun. 2016;74:85-93. doi:10.1016/j.jaut.2016.06.009.
  8. Manfredo Vieira S, Hiltensperger M, Kuman V, et al. Translocation of a gut pathobiont drives autoimmunity in mice and humans. Science. 2018;359(6380):1156-1161. doi:10.1126/science.aar7201.
  9. Salminen S, Bouley C, Boutron-Ruault MC, et al. Functional food science and gastrointestinal physiology and function. Br J Nutr. 1998;80(S1):S147-S171.
  10. 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:10.1016/j.jaut.2017.03.009.
  11. Alexander KL, Targan SR, Elson CO 3rd. Microbiota activation and regulation of innate and adaptive immunity. Immunol Rev. 2014;260(1):206-220. doi:10.1111/imr.12180.
  12. Hand TW, Dos Santos LM, Bouladoux N, et al. Acute gastrointestinal infection induces long-lived microbiota-specific T-cell responses. Science. 2012;337(6101):1553-1556. doi:10.1126/science.1220961.
  13. Ruff WE, Kriegel MA. Autoimmune host-microbiota interactions at barrier sites and beyond. Trends Mol Med. 2015;21(4):233-244. doi:10.1016/j.molmed.2015.02.006.
  14. 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:10.1016/j.ijpharm.2018.11.020.

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