Diet is an influencer of the composition and function of the microbiota [29]. Adults with rheumatoid arthritis may be improved by vegan or Mediterranean diet [30–32]. In paediatric CD, feeding with exclusive enteral nutrition (EEN) has been shown to exert a positive influence on intestinal microbiota, and to have an anti-inflammatory and healing effect on the intestinal mucosa, leading to an improved nutritional status and a reduced need for corticosteroids [33]. In Europe, paediatric patients with CD receive EEN during the first six to eight weeks of treatment. Two other diets, SCD and Crohn’s disease exclusion diet, have shown positive results in CD [22, 34]. The two diets resemble each other, but are not identical. So far, the only dietary intervention published, conducted on children with JIA, was performed by our group, investigating the anti-inflammatory effect of exclusive enteral nutrition (EEN). The study included only seven children, treated for 3–8 weeks; all of them had an anti-inflammatory effect in clinical and laboratory results, but to varying degrees [35].
In this study, SCD as a complementary treatment in patients with JIA resulted in a significant improvement in morning stiffness, pain, physical function and a significant increase in faecal butyrate concentration, indicating an anti-inflammatory effect from SCD. Participants of this study had a low to median disease activity at inclusion; approximately half of them had morning stiffness and pain as remaining complaints from the disease, in spite of medical treatment. We aimed for a dietary intervention of at least four weeks. Morning stiffness, pain and physical function improved already after two to three weeks in the majority of participants. The inflammatory activity in two patients increased very shortly after inclusion in the study, and the arthritis in those two children did not respond to treatment. In the remaining five with arthritis at inclusion, no clinical sign of arthritis could be found after four/five weeks on SCD. The flare in the two children with no response had already started at inclusion and may be unrelated to SCD, but SCD could not decrease the flare of the disease during the study period.
Laboratory analysis results did not change significantly during the study period, but only four of the children had an ESR > 10 at inclusion. The JADAS27 decreased, but not significantly, and the results could be biased since JADAS27 includes the researcher’s subjective assessment of disease activity in the patient.
Our results of a significant increase in butyrate and an increasing, yet non-significant, level of SCFAs in faeces are not surprising, possibly providing confirmation that participants had followed the diet. Fibres and starches found in fruits and vegetables are vital substrates for the production of butyrate and other SCFAs. The SCFAs are proven to have many beneficial functions, such as being an energy substrate for the epithelial cells of the colon. However, they also seem to have more complex functions, such as regulating gene expression and contributing to an anti-inflammatory state of the intestine. Several studies have shown that these microbial metabolites, especially butyrate, have profound effects on T cells, directly and indirectly regulating their differentiation [19, 36]. Low dietary fibres may cause catabolism of the mucous layer, leading to increased permeability and allowing increased contact between luminal bacteria and the epithelium [37]. The composition of the bacterial flora, the diet of the host, and the transit time in the gut are some of the factors influencing the production of SCFAs. While the butyrate level increased in faecal samples from the participants, we do not know if butyrate is involved in regulation of inflammation in children with JIA; most likely, it plays an anti-inflammatory role.
We can only speculate that the elimination of processed food, additives and emulsifiers and restriction of carbohydrates and dairy products play an immunological role in JIA. Processed food often contains exogenous advanced glycation end products (AGEs), these are common in food products that have been heated. Exogenously added AGEs have been shown in animal studies to influence immune and epithelial cells by activating the receptor for advanced glycation end products in various types of cells, such as immune cells, endothelial cells, myocytes, and neurons, but studies in humans have not come that far [38]. The high-fructose corn syrup (HFCS) is a popular sweetener in the food industry, for example in soda. High consumers of sodas have been shown to have an increased risk of arthritis in adults compared with low consumers [39]. HFCS is decreased in SCD compared with in a conventional diet, we lack knowledge about the occurrence of AGEs.
This study on SCD comprised only fifteen patients, and the arthritis was not verified by ultrasound, which are the major weaknesses of the study. Also, children with different categories of the disease on different medical treatments were included, which may have confounded interpretation of results. It would have been preferable to have a control group, which was difficult to arrange in practice.
Making the home-cooked meals required by the SCD was a challenge for many of the families, but the fairly rapid improvement in the majority of the children motivated both parents and children. A strength of the study was that the SCD diet is well-described and studied in children with inflammatory conditions in the digestive tract. Much research remains to understand how diet influences the immune system in children with JIA and how long-lasting the effects are. The results from this study suggest that diet may provide a promising complementary treatment modality for children with JIA.