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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.1,2
Gut Microbes and Autoimmune Disease
Gut microbiota are implicated in almost every chronic condition. An imbalanced intestinal microbiome may drive inflammatory conditions such as obesity, diabetes, inflammatory bowel disease, colorectal cancer, and immunosenescence in the elderly,3 as well as endocrine diseases4 and autoimmune conditions. The accumulation of microbes that are perceived as pathogens in the microbiome likely contributes to the inflammatory cascade that impacts immune function and tolerance.5
Sensitive periods for the microbiome include childhood and pregnancy, during which the microbiome may undergo profound changes.6 Differences have been suggested to 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).6 These types of alterations in the microbiome may trigger both local and systemic inflammation.6 In addition, during childhood, the gut microbiome is 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, Sneathis spp.), while Cesarean section–delivered infants harbor bacterial communities similar to those found on the skin surface (Staphylococcus, Corynebacterium, and Propionibacterium).6
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 number of exciting new studies have focused on the microbiome, therapeutic probiotics, and autoimmune conditions including systemic lupus erythematosus (SLE), type 1 diabetes, and more.7–10 Even central nervous system autoimmune conditions may benefit from treatments that target the microbiome and its activity.11
In one 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.12 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.12
“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.
The gut microbiota can exert immunomodulatory effects,13 particularly through antigen-specific T cells14 and their related anti- and pro-inflammatory cytokines, as well as several other mediators of inflammation.4 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.15
Recent research shows that probiotic treatments may impact the immune system by influencing the activity of cells in the gut.8,16,17 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:18 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.18 A 2021 meta-analysis that included 18 randomized controlled trials found that the consumption of Lactobacillus (L.) plantarum strains promoted host immunity by significantly increasing levels of the anti-inflammatory cytokine IL-10 while significantly reducing levels of IL-4 and pro-inflammatory cytokines IFN-γ and TNF-α.19
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 and that this shift may be prevented by dietary intervention.8 The gut microbiota composition is influenced by diet, and dysbiosis may be associated with the consumption of Western-style diets, which are rich in fats and high in sugar.20 In animal models, diet has been shown to profoundly impact microbial structure; this type of dysbiosis closely resembles the dysbiosis seen in obese humans.20 A 2014 clinical study found that high-fat diets consisting solely of animal-based foods dramatically shifted the structure of the gut microbiota in human participants20,21 while a 2021 cross-over clinical trial of patients with ulcerative colitis in remission found that a low-fat, high-fiber diet decreased markers of inflammation and reduced measures of intestinal dysbiosis.22
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.23 It has even been hypothesized that the increasing incidence of autoimmune diseases could be due to considerable shifts in the gut microbiota.23 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
- Proal AD, Albert PJ, Marshall TG. The human microbiome and autoimmunity. Curr Opin Rheumatol. 2013;25(2):234-240. doi:10.1097/BOR.0b013e32835cedbf.
- Paray BA, Albeshr MF, Jan AT, Rather IA. Leaky gut and autoimmunity: an intricate balance in individuals health and the diseased state. Int J Mol Sci. 2020;21(24):9770. doi:10.3390/ijms21249770.
- 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.
- 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.
- 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.
- De Luca F, Shoenfeld Y. The microbiome in autoimmune diseases. Clin Exp Immunol. 2018;195(1):74-85. doi:10.1111/cei.13158.
- 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.
- 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:10.1097/BOR.0000000000000574.
- Groele L, Szajewska H, Szalecki M, et al. Lack of effect of Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 on beta-cell function in children with newly diagnosed type 1 diabetes: a randomised controlled trial. BMJ Open Diabetes Res Care. 2021;9(1):E1523. doi:10.1136/bmjdrc-2020-001523.
- de Groot P, Nikolic T, Pellegrini S, et al. Faecal microbiota transplantation halts progression of human new-onset type 1 diabetes in a randomised controlled trial. Gut. 2021;70(1):92-105. doi:10.1136/gutjnl-2020-322630.
- 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.
- 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:10.1126/science.aar7201.
- 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.
- Alexander KL, Targan SR, Elson CO. Microbiota activation and regulation of innate and adaptive immunity. Immunol Rev. 2014;260(1):206-220. doi:10.1111/imr.12180.
- 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.
- 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:10.1016/j.cellimm.2018.10.005.
- Shi HY, Zhu X, Li WL, et al. Modulation of gut microbiota protects against viral respiratory tract infections: a systematic review of animal and clinical studies. Eur J Nutr. 2021;60(8):4151-4174. doi:10.1007/s00394-021-02519-x.
- 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.
- Zhao W, Peng C, Sakandar HA, Kwok L-Y, Zhang W. Meta-analysis: randomized trials of Lactobacillus plantarum on immune regulation over the last decades. Front Immunol. 2021;12:643420. doi:10.3389/fimmu.2021.643420.
- Martinez KB, Leone V, Chang EB. Western diets, gut dysbiosis, and metabolic diseases: are they linked? Gut Microbes. 2017;8(2):130-142. doi:10.1080/19490976.2016.1270811.
- David LA, Maurice CF, Carmody RN, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505(7484):559-563. doi:10.1038/nature12820.
- Fritsch J, Garces L, Quintero MA, et al. Low-fat, high-fiber diet reduces markers of inflammation and dysbiosis and improves quality of life in patients with ulcerative colitis. Clin Gastroenterol Hepatol. 2021;19(6):1189-1199. doi:10.1016/j.cgh.2020.05.026.
- 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:10.1155/2019/7546047.