insights
How Do Gut Bacteria Migrate Throughout the Body?
In recent years, research has demonstrated how intestinal permeability allows bacteria, T cells, and food antigens to migrate outside of the gut, thereby laying the basis for autoimmune disease. The path of migration from the gut to other areas of the body affects the immune system and offers avenues for intervention.
Bacteria travels from the gut through the lymphs or in the blood, utilizing dendritic cells or macrophages as carriers. Deposits in the joints or entheses lead to reactive arthritis.1 Activated T cells also use the lymphatic system; in particular, CCR9 and alpha-4 beta-7 antigens have been found in the pancreas of diabetics and in the brains of patients with multiple sclerosis.2
When antibodies or bacteria ‘pose’ as self-antigens, which the body normally tolerates, this molecular mimicry opens the door for a multi-pronged immune response that can create an autoimmune condition.3 For example, H. pylori infection has been linked to the development of diverse diseases such as immune thrombocytopenic purpura, iron-deficiency anemia, vitamin D deficiency, and diabetes. Research suggests that neurological and dermatological disorders, lung cancer, and growth retardation in children can also be traced to the manipulation of the immune system by H. pylori.3 Free-form DNA may be another transport method, as in the case where periodontal bacterial DNA was found in the joints of patients with rheumatoid arthritis.4
Two rodent studies have demonstrated successful approaches to preventing the dispersal of antigens, bacteria, and T cells beyond the gut. A mouse study highlighted the importance of commensal bacteria—arthritis was successfully suppressed by the enteral introduction of Prevotella histicola.5 In germ-free mice, neutralizing interleukin-17 reduced the T helper 17 population in the spleen, preventing the development of arthritis.6
As Dr. Fasano states, “What happens in the gut doesn’t stay in the gut,” and this is increasingly borne out by research. Understanding the mechanisms that allow antigens to cross the gut barrier will continue to inform autoimmune disease prevention and treatment strategies.
Learn more about the underlying mechanisms for autoimmunity, and the resulting treatment options, at IFM’s 2018 Annual International Conference.
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References
- Berthelot JM, Claudepierre P. Trafficking of antigens from gut to sacroiliac joints and spine in reactive arthritis and spondyloarthropathies: mainly through lymphatics? Joint Bone Spine. 2016;83(5):485-490. doi:1016/j.jbspin.2015.10.015.
- Kizil C, Kyritsis N, Brand M. Effects of inflammation on stem cells: together they strive? EMBO Rep. 2015;16(4):416-426. doi:15252/embr.201439702.
- Chmiela M, Gonciarz W. Molecular mimicry in Helicobacter pylori infections. World J Gastroenterol. 2017;23(22):3964-3977. doi:3748/wjg.v23.i22.3964.
- Martinez-Martinez RE, Abud-Mendoza C, Patiño-Marin N, Rizo-Rodríguez JC, Little JW, Loyola-Rodríguez JP. Detection of periodontal bacterial DNA in serum and synovial fluid in refractory rheumatoid arthritis patients. J Clin Periodontol. 2009;36(12):1004-1010. doi:1111/j.1600-051X.2009.01496.x.
- Marietta EV, Murray JA, Luckey DH, et al. Suppression of inflammatory arthritis by human gut-derived Prevotella histicola in humanized mice. Arthritis Rheumatol. 2016;68(12):2878-2888. doi:1002/art.39785.
- Wu HJ, Ivanov II, Darce J, et al. Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. 2010;32(6):815-827. doi:10.1016/j.immuni.2010.06.001.
