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Immunology and the Microbiome

Probiotic kimchi
            Read time: 3 minutes

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. Although 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

Sensitive periods for the microbiome include childhood and pregnancy, during which the microbiome may undergo profound changes.5 A 2012 study suggests that differences exist in pregnant women between their first and third trimesters; in the last months of pregnancy, researchers noticed an abundance of Proteobacteria and Actinobacteria and a depletion of Faecalibacterium (a butyrate producer with anti?inflammatory effects). During childhood, the gut microbiome may be influenced by environmental factors such as geographic area, breastfeeding, exposure to antibiotics, and method of delivery. Vaginally delivered infants acquire bacterial communities resembling their own mother’s vaginal microbiota (Lactobacillus, Prevotella, Sneathia spp.), while Cesarean section–delivered infants harbor bacterial communities similar to those found on the skin surface (Staphylococcus, Corynebacterium, and Propionibacterium). These types of alterations in the microbiome may trigger both local and systemic inflammation.5

This line of research points to the potential for treatment and prevention of autoimmune conditions using therapies directed at the microbiome, as the loss of immune tolerance can be caused by microbial composition changes. A recent review article described a number of exciting studies focused on the microbiome, therapeutic probiotics, and autoimmune conditions, including systemic lupus erythematosus (SLE), type 1 diabetes, and more.6,7 Even central nervous system autoimmune conditions may benefit from treatments that target the microbiome and its activity.8

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.9 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.9

“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,10 particularly through antigen-specific T cells11 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.12

Some recent research shows that probiotic treatments may impact the immune system by influencing the activity of cells in the gut.7,13 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: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. While this research was conducted in vitro, the results suggest that probiotic species acting alone may not result in a clinical effect; rather, bacteria interact with and alter metabolic and immune byproducts.14

Recent studies also highlight that a breach of the intestinal barrier through dysbiosis and translocation of commensal bacteria to other organs may trigger several autoimmune pathways.7 This shift may be prevented by dietary intervention.7 The gut microbiota may also be influenced by diet, and dysbiosis may be associated with the consumption of Western-style diets, which are rich in fats and high in sugar.15 In animal models, diet has been shown to profoundly impact microbial structure; this type of dysbiosis closely resembles the dysbiosis seen in obese humans. One study showed that high-fat diets consisting solely of animal-based foods dramatically shifted the structure of the gut microbiota in human participants.15

A better understanding of the interactions between the microbiome and the immune system may lead to new ways of treating and preventing autoimmune dysfunction. Innate and adaptive immunity play an important role in the containment and clearance of microbial pathogens.16 It has even been hypothesized that the increasing incidence of autoimmune diseases could be due to considerable shifts in the gut microbiota.16 To learn more about both the genetic and environmental factors that contribute to autoimmune diseases, and ways to rebalance the microbiome to enhance health and well-being, please follow the links below:

Want to learn more about building immune resilience? ATTEND PLMI’S EIGHT ANNUAL THOUGHT LEADERS CONSORTIUM ON IMMUNE REJUVENATION IN A PANDEMIC ERA

Innate Immunity: Diet and Lifestyle Support

The Role of the Microbiome in Immune-Related Diseases

Learn More About Immune Imbalance

References

  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 Luca F, Shoenfeld Y. The microbiome in autoimmune diseases. Clin Exp Immunol. 2019;195(1):74-85. doi:1111/cei.13158
  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:1111/imm.12765
  7. Dehner C, Fine R, Kriegel MA. The microbiome in systemic autoimmune disease: mechanistic insights from recent studies. Curr Opin Rheumatol. 2019;31(2):201-207. doi:1097/BOR.0000000000000574
  8. 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
  9. 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
  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: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:1111/imr.12180
  12. 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
  13. Marietta E, Horwath I, Balakrishnan B, Taneja V. Role of the intestinal microbiome in autoimmune diseases and its use in treatments. Cell Immunol. 2019;339:50-58. doi:1016/j.cellimm.2018.10.005
  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:1016/j.ijpharm.2018.11.020
  15. Martinez KB, Leone V, Chang EB. Western diets, gut dysbiosis, and metabolic diseases: are they linked? Gut Microbes. 2017;8(2):130-142. doi:1080/19490976.2016.1270811
  16. Xu H, Liu M, Cao J, et al. The dynamic interplay between the gut microbiota and autoimmune diseases. J Immunol Res. 2019;2019:7546047. doi:1155/2019/7546047

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