If you’ve been diagnosed with rheumatoid arthritis then you might be wondering ‘is rheumatoid arthritis hereditary?’ In this article, we answer this question for you, with a review of the medical literature.
How Does Rheumatoid Arthritis Correlate With our Genetics?
Researchers have found that there are more than 100 places in our DNA that affect an individual’s possibility of developing rheumatoid arthritis. Much of this is related to the cells that produce the material in our joints [1].
The genes involved in immune function and joint tissue formation are variable (epigenetics) and can be influenced by other factors. Just because you have a genetic disposition to a condition and perhaps a member of your family may have the condition, it doesn’t mean that you will automatically develop it.
Immune effects on Rheumatoid Arthritis
In rheumatoid arthritis, the cells that make up your joint are all affected by the immune system and joint inflammation. This leads to tissue destruction, structural damage, and disability. Rheumatoid arthritis is also characterised by systemic inflammation and increased cardiovascular risk [2].
Changes in immune system function also affect how bone is repaired and this too is partially inherited. There is also a partially genetic cause for some of the damage to bones seen in rheumatoid arthritis [3].
Genetic Correlation with Other Conditions
Interestingly, there also is evidence that children of parents with rheumatoid arthritis (RA) have a 30% increased risk of developing autism or autism spectrum disorder (ASD). Both maternal and paternal RA were associated with an increased risk of ASD, suggesting that genetic factors are associated with both the etiology of both RA and ASD [4]. Therefore, there is some evidence that there is a rheumatoid arthritis hereditary issue.
Genetic Influences on Rheumatoid Arthritis Outcome and Treatment
In the future, it is hoped that new techniques in mapping genes will enable a more precise approach in the management of rheumatoid arthritis [5].
Is Rheumatoid Arthritis Hereditary? Inheriting the genetics of your gut microbiome
The gut microbiome is a complex colony of bacteria and viruses inherited primarily from your mother. It can influence gene expression and immune regulation. Gut microbes can travel through the body, often with the help of the immune system, and because of this, we can assume that each part of the body has its own microbiome. Joints are no exception to this.
In rheumatoid arthritis, the bacteria found in the joints can come from the oral cavity or the gut. Some organisms, such as Porphyromonas gingivalis, have been implicated in causing epigenetic changes at the joint that contributes to rheumatoid arthritis.
Several lines of evidence challenge the idea that rheumatoid arthritis is mainly an autoimmune disorder. So this suggests that rheumatoid arthritis might be induced by epigenetic changes in joint fluid cells, stressed by the excessive movement of pathogenic bacteria from a poorly cultivated gut, lung, or oral microbiome into the joints [6].
The Importance of Probiotics in Rheumatoid Arthritis
Research has demonstrated that subtle differences in the strains of some probiotic bifidobacterium and other species can alter the incidence of rheumatoid arthritis [7].
A review study also highlighted the importance of probiotic supplementation in rheumatoid arthritis where regulated trials have shown that particular probiotic supplements have anti-inflammatory benefits which ‘helps people with RA enhance daily activities and alleviates symptoms’ [8].
The Gut Microbiome and Rheumatoid Arthritis
The microbiome is strongly associated with the development of rheumatoid arthritis. So it could possibly be used in the future as a way to identify people with an increased risk of developing RA [9].
Having the right gut biome means that the gut bacteria produce cells that regulate immune function and reduce inflammation in the intestines [10]. Another study has also found that some organisms in the microbiome have also been found to be characteristic of rheumatoid arthritis, with some rare organisms taking a lead role as the host develops the condition [11].
Is Rheumatoid Arthritis Hereditary or is it Something Else?
In conclusion, genetics do influence the likelihood of getting rheumatoid arthritis but over 100 places on our DNA are involved. The genes that show are highly variable and many factors can influence the genes that show (epigenetics) including an individual’s microbiome.
Gut bacteria have been studied extensively enough to prove that they play a crucial role in disease onset, severity, and response to treatment.
So, if the microbiome is such a big player in rheumatoid arthritis, what goes wrong and what can we do to help our microbiome and therefore our outcomes? Well, we need to observe, unpack, and…digest!
What we can do to improve our microbiome?
Different organisms in our microbiome thrive or starve based on the foods we eat and the life we live. We also know this has a big impact on immune control and many other critical variables.
The diet can cause or reduce inflammation and this effect is due to changes in the gut microbiome. Dysbiosis occurs when the bacteria in your gastrointestinal tract becomes unbalanced. This causes problems such as increased intestinal permeability (where bacteria can pass into the bloodstream) and inflammation.
A healthy microbiome is anti-inflammatory while a ‘bad microbiome’ causes more inflammation and potentially even autoimmunity.
Diet changes the microbiome by feeding some organisms more than others. A high-fiber diet such as a vegetarian or vegan diet is associated with more microbiome diversity and less inflammation compared to a standard “western” omnivorous diet.
A 13-Month Study that Might Conflict with Rheumatoid Arthritis Hereditary Claims?
One 13 month study, compared patients on a vegan and the lacto-vegetarian diet with an ordinary omnivore diet. After 1 month, patients within the intervention group showed significant clinical improvements. Compared to those in the omnivore group they had significantly less tender and swollen joints and pain. Their clinical test results were also significantly better (CRP and ESR) [12].
Adding fiber by itself was not as effective as fiber-rich, whole-diet interventions. This suggests that actual food also has other beneficial nutrients beyond just fiber [12].
The effects of increasing fiber can happen rapidly, within 30 days and the effects can also last for 40 days following cessation of the high-fiber diet [13].
Resistant starches promote anti-inflammatory response and a resistant starch diet ‘might be a promising therapy especially in the early stage of RA’[14].
Intestinal barriers can also be caused by increased life stress, as can gut dysbiosis. These two critical factors are both promoted by urban lifestyles and are components of poor immune control and resultant autoimmunity. There is increasing evidence to support that gut dysbiosis and a disturbed gut biome occur in patients with early and long-standing rheumatoid arthritis [15].
So, can Dietary Changes Treat Rheumatoid Arthritis?
A balanced approach depending on the stage of the disease process is a sensible approach. If trying to prevent rheumatoid arthritis, or in the early stages, it is possible that dietary intervention alone may be sufficient. This may even be true in individuals with active joint damage, but there is certainly a threshold where medication is appropriate to prevent joint damage.
It is important to note that bony changes and joint damage may remain for the rest of a patient’s life, and the administration of DMARDs or similar medication may also halt that damage. This can also allow for the opportunity to implement dietary and gut microbiome-based interventions, while not accruing permanent joint damage along the health journey.
Exercise, microbiome, and immune control
Perhaps the simplest, yet most challenging intervention, physical exercise has been shown to improve gut microbiome diversity. However, the benefits of exercise may take 8 weeks or more to show. This is important to understand, as short-term exercise may cause more inflammation, while long-term exercise improves both the microbiome and immune control [16].
So, is Rheumatoid Arthritis Hereditary? There are variables, and we can influence them!
To sum things up, there is evidence to suggest that rheumatoid arthritis hereditary concerns should be limited. Instead, our microbiome really matters and may be the difference between expressing rheumatoid arthritis as a disease, or not. It defines the difference between controlling the disease effectively or allowing it to ruin your ability to use your joints without pain. Our single biggest intervention to help the microbiome is diet, so remember that you’re not only feeding yourself but also your gut symbionts!
References for: Is Rheumatoid Arthritis Hereditary:
[1] Ge X, Frank-Bertoncelj M, Klein K, et al. Functional genomics atlas of synovial fibroblasts defining rheumatoid arthritis heritability. Genome Biol. 2021;22(1):247. Published 2021 Aug 25. doi:10.1186/s13059-021-02460-6
[2] Payet M, Dargai F, Gasque P, Guillot X. Epigenetic Regulation (Including Micro-RNAs, DNA Methylation and Histone Modifications) of Rheumatoid Arthritis: A Systematic Review. Int J Mol Sci. 2021;22(22):12170. Published 2021 Nov 10. doi:10.3390/ijms222212170
[3] Bernardes M, Durães C, Oliveira A, Martins MJ, Lucas R, Costa L, Pereira JG, Ramos I, Machado JC, Simões-Ventura F. LRP5 gene polymorphisms and radiographic joint damage in rheumatoid arthritis patients. Osteoporos Int. 2018 Oct;29(10):2355-2368. doi: 10.1007/s00198-018-4625-3. Epub 2018 Jul 17. PMID: 30019084.
[4] Rom AL, Wu CS, Olsen J, Jawaheer D, Hetland ML, Mørch LS. Parental Rheumatoid Arthritis and Autism Spectrum Disorders in Offspring: A Danish Nationwide Cohort Study. J Am Acad Child Adolesc Psychiatry. 2018 Jan;57(1):28-32.e1. doi: 10.1016/j.jaac.2017.10.002. Epub 2017 Oct 9. PMID: 29301665.
[5] Viatte S, Barton A. Genetics of rheumatoid arthritis susceptibility, severity, and treatment response. Semin Immunopathol. 2017;39(4):395-408. doi:10.1007/s00281-017-0630-4
[6] Berthelot JM, Bandiaky ON, Le Goff B, Amador G, Chaux AG, Soueidan A, Denis F. Another Look at the Contribution of Oral Microbiota to the Pathogenesis of Rheumatoid Arthritis: A Narrative Review. Microorganisms. 2021 Dec 28;10(1):59. doi: 10.3390/microorganisms10010059. PMID: 35056507; PMCID: PMC8778040.
[7] Jeong Y, Jhun J, Lee SY, et al. Therapeutic Potential of a Novel Bifidobacterium Identified Through Microbiome Profiling of RA Patients With Different RF Levels. Front Immunol. 2021;12:736196. Published 2021 Nov 15. doi:10.3389/fimmu.2021.736196
References for Diet Changes
[8] Bungau SG, Behl T, Singh A, et al. Targeting Probiotics in Rheumatoid Arthritis. Nutrients. 2021;13(10):3376. Published 2021 Sep 26. doi:10.3390/nu13103376
[9] Chen Y, Ma C, Liu L, et al. Analysis of gut microbiota and metabolites in patients with rheumatoid arthritis and identification of potential biomarkers. Aging (Albany NY). 2021;13(20):23689-23701. doi:10.18632/aging.203641
[10] Smith PM, Howitt MR, Panikov N, et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 2013;341(6145):569-573. doi:10.1126/science.1241165
[11] Chen J, Wright K, Davis JM, et al. An expansion of rare lineage intestinal microbes characterizes rheumatoid arthritis. Genome Med. 2016;8(1):43. Published 2016 Apr 21. doi:10.1186/s13073-016-0299-7
[12] Wagenaar CA, van de Put M, Bisschops M, et al. The Effect of Dietary Interventions on Chronic Inflammatory Diseases in Relation to the Microbiome: A Systematic Review. Nutrients. 2021;13(9):3208. Published 2021 Sep 15. doi:10.3390/nu13093208
[13] Dürholz K, Hofmann J, Iljazovic A, et al. Dietary Short-Term Fiber Interventions in Arthritis Patients Increase Systemic SCFA Levels and Regulate Inflammation. Nutrients. 2020;12(10):3207. Published 2020 Oct 20. doi:10.3390/nu12103207
[14] Bai Y, Li Y, Marion T, Tong Y, Zaiss MM, Tang Z, Zhang Q, Liu Y, Luo Y. Resistant starch intake alleviates collagen-induced arthritis in mice by modulating gut microbiota and promoting concomitant propionate production. J Autoimmun. 2021 Jan;116:102564. doi: 10.1016/j.jaut.2020.102564. Epub 2020 Nov 14. PMID: 33203617.
[15] Koh A, De Vadder F, Kovatcheva-Datchary P, Bäckhed F. From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites. Cell. 2016 Jun 2;165(6):1332-1345. doi: 10.1016/j.cell.2016.05.041. PMID: 27259147.
[16] Miranda-Comas G, Petering RC, Zaman N, Chang R. Implications of the Gut Microbiome in Sports. Sports Health. 2022 Jan 17:19417381211060006. doi: 10.1177/19417381211060006. Epub ahead of print. PMID: 35034531.