Intestinal permeability is highly implicated in the onset and progression of autoimmune conditions.1,2 Autoimmune patients frequently experience chronic pain,3 and yet, nonsteroidal anti-inflammatory drugs (NSAIDs) are known to increase intestinal permeability and can lead to endotoxemia, enteropathy, and further complications.4,5
Reducing side effects from pain medications in autoimmune patients is possible. Helen Messier, MD, shares ways to support gut and immune health while also addressing pain related to autoimmunity.
Gut microflora can be modulated by extrinsic factors, including dietary habits, lifestyle, infection, and early microbiota exposure, as well as intrinsic factors such as genetic background, metabolites, immunity, and hormones.6 The gut-brain axis, which provides a two-way homeostatic communication between the gastrointestinal tract and the central nervous system, plays an integral role in human health and disease.6,7 In recent years, it has been hypothesized that the increasing incidence of autoimmune diseases may be due, in part, to shifts in the gut microbiota.8
Dysbiosis in the gut microbiome may trigger gut barrier dysfunction such as changes in tight junctions, mucous layers, and secretion of immunoglobulin A and intraepithelial lymphocytes.6 In particular, research suggests that gut dysbiosis may influence a systemic immune response and impact pain thresholds in some autoimmune conditions like Guillian-Barré syndrome,7 systemic lupus erythematous,8 multiple sclerosis (MS),9 and rheumatoid arthritis (RA).8,10
Is it possible to manage the pain of autoimmune diseases by changing the composition of the gut microbiota? Research is still in its infancy, but some studies show promising results. A small, single-blind dietary intervention found that a low-fat vegan diet may improve RA symptoms, including the degree of pain, joint tenderness, and joint swelling.11 One randomized clinical trial found that a gluten-free vegan diet decreases immunoglobulin G (IgG), an often elevated proinflammatory antibody in RA patients.12
Some bacterial probiotic strains have been shown to reduce the number of inflammatory monocytes in MS patients.13 In 2019, a prospective randomized double-blind placebo-controlled clinical trial was initiated to evaluate whether probiotic treatment with Saccharomyces boulardii could improve mental health, quality of life, fatigue, pain, and indices of inflammation and oxidative stress in patients with MS.14 The results of this study are forthcoming.
Researchers continue to explore the microbiome as a means of discovering safe and non-pharmacologic methods for managing the painful symptoms of autoimmune disorders. A deep understanding of the interplay between the gut microbiota and the central nervous system may help in the discovery of new therapeutic targets for autoimmune patients. It remains unclear, however, whether dysfunction in gut microbiota is the cause or the consequence of autoimmune disease. Either way, there is promising evidence that modifying the microbiome may help reduce pain for at least some patients with these common diseases
For further educational resources on pain and autoimmune diseases, please follow the links provided below.
Learn more about the Functional Medicine Guide to Autoimmunity
- Fasano A. Leaky gut and autoimmune diseases. Clin Rev Allergy Immunol. 2012;42(1):71-78. doi:1007/s12016-011-8291-x
- Sturgeon C, Fasano A. Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases. Tissue Barriers. 2016;4(4):e1251384. doi:1080/21688370.2016.1251384
- Mifflin KA, Kerr BJ. Pain in autoimmune disorders. J Neurosci Res. 2017;95(6):1282-1294. doi:1002/jnr.23844
- Utzeri E, Usai P. Role of non-steroidal anti-inflammatory drugs on intestinal permeability and nonalcoholic fatty liver disease. World J Gastroenterol. 2017;23(22):3954-3963. doi:3748/wjg.v23.i22.3954
- Bjarnason I, Takeuchi K. Intestinal permeability in the pathogenesis of NSAID-induced enteropathy. J Gastroenterol. 2009;44(Suppl 19):23-29. doi:1007/s00535-008-2266-6
- Zhu S, Jiang Y, Xu K, et al. The progress of gut microbiome research related to brain disorders. J Neuroinflammation. 2020;17(1):25. doi:1186/s12974-020-1705-z
- Catanzaro R, Anzalone M, Calabrese F, et al. The gut microbiota and its correlations with the central nervous system disorders. Panminerva Med. 2015;57(3):127-143.
- Xu Huihui, Liu M, Cao J, et al. The dynamic interplay between gut microbiota and autoimmune diseases. J Immunol Res. 2019;2019:7546047. doi:1155/2019/7546047
- Rodriguez M, Wootla B, Anderson G. Multiple sclerosis, gut microbiota and permeability: role of tryptophan catabolites, depression, and the driving down of local melatonin. Curr Pharm Des. 2016;22(40):6134-6141. doi:2174/1381612822666160915160520
- Alwarith J, Kahleova H, Rembert E, et al. Nutrition interventions in rheumatoid arthritis: the potential use of plant-based diets. A review. Front Nutr. 2019;10(6):141. doi:3389/fnut.2019.00141
- McDougall J, Bruce B, Spiller G, Westerdahl J, McDougall M. Effects of a very low-fat, vegan diet in subjects with rheumatoid arthritis. J Altern Complement Med. 2002;8(1):71-75. doi:1089/107555302753507195
- Hafström I, Ringertz B, Spångberg A, et al. A vegan diet free of gluten improves the signs and symptoms of rheumatoid arthritis: the effects on arthritis correlate with a reduction in antibodies to food antigens. Rheumatology (Oxford). 2001;40(10):1175-1179. doi:1093/rheumatology/40.10.1175
- Tankou SK, Regev K, Healy BC, et al. A probiotic modulates the microbiome and immunity in multiple sclerosis. Ann Neurol. 2018;83(6):1147-1161. doi:1002/ana.25244
- Aghamohammadi D, Ayromlou H, Dolatkhah N, Jahanjoo F, Shakouri SK. The effects of probiotic Saccharomyces boulardii on the mental health, quality of life, fatigue, pain, and indices of inflammation and oxidative stress in patients with multiple sclerosis: study protocol for a double-blind randomized controlled clinical trial. Trials. 2019;20(1):379. doi:1186/s13063-019-3454-9