Diet affects the composition and function of the microbiota, which may have implications on health . In this study, SCD as a complementary treatment in patients with JIA resulted in a significant improvement in morning stiffness, pain, and physical function. We also found a significant decrease in inflammatory proteins in the seven children with arthritis at inclusion. An increase in faecal butyrate concentration from four weeks of SCD in fifteen children coincided at a group level with improvement in clinical variables.
Participants in 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. The clinical assessments of pain, morning stiffness, global assessment VAS, and physical function improved already after two to three weeks in the majority of participants and pointed to a positive effect from SCD. Disease activity according to JADAS27 decreased, but not significantly – which was not surprising given the low JADAS27 at inclusion. 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.
Laboratory analysis results of blood samples did not change significantly during the study period, but only four of the children had an ESR > 10 mm/h at inclusion. Furthermore, conventional laboratory tests for inflammation are not very sensitive in JIA . However, when we studied the seven children with arthritis at inclusion, one of the most central chemokines in inflammation, TNF-alpha, and its apoptosis-inducing ligand (TRAIL) decreased significantly from SCD during four weeks. Both MCP-1 and CX3CL1 also decreased. They have shown significant chemoattractant roles in recruiting inflammatory cells to synovial joints in RA and have both been associated with disease activity scores in RA [32, 33]. Adenosine deaminase (ADA) is considered one of the key enzymes of purine metabolism; we can only speculate that the decreased concentration from SCD was due to the dietary change . Interleukin (IL)10- and IL10R-dependent signalling modulates innate and adaptive immune responses in the murine as well as the human gastrointestinal tract. The decrease in soluble IL10RA and IL10RB from SCD in this study most likely relates to a decreased need for those receptors in a low inflammatory state . The laboratory results from a multiplex system, in the seven children with arthritis at inclusion, showed an anti-inflammatory effect at a group level, raising the hypothesis that four weeks of SCD most likely had a positive impact on the inflammatory process, but not in every individual. One could also speculate that the impact in two of the children was too weak and possibly too short to affect the inflammatory process.
Our results of a significant increase in butyrate and an increasing, yet non-significant, level of SCFAs in faeces are not surprising, since 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, contributing to an anti-inflammatory state of the intestine. Several studies have shown that these microbial metabolites, especially butyrate – in addition to being an energy substrate for the epithelial cells of the colon – have profound effects on T cells, directly and indirectly regulating their differentiation [19, 36]. New findings also suggest that butyrate can suppress arthritis by influencing the development and function of Breg cells in mice .
SCD contains large amounts of dietary fibres. Low dietary fibres may cause catabolism of the mucous layer, leading to increased permeability and allowing increased contact between luminal bacteria and the epithelium . 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 elimination of processed food, additives, and emulsifiers, and restriction of carbohydrates and dairy products play an immunological role in JIA. Processed food often contains high amounts of exogenous advanced glycation end products (AGEs), which are common in food products that have been heated. Exogenously added AGEs have been shown in animal studies to affect immune and epithelial cells by activating the receptors for AGEs in various types of cells, such as immune cells, endothelial cells, myocytes, and neurons, but studies in humans have not come that far . 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 . 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 was a challenge to coordinate inclusion of a patient with a period of two/three months of a stable, low to median inflammatory state. Also, it would have been preferable to have a control group, which was difficult to organise in practice.
Making the home-cooked meals required in 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 is well-described and studied in children with inflammatory conditions in the digestive tract, as one of two diets studied in paediatric IBD. The results from this study suggest that specific carbohydrate diet may provide a promising complementary treatment modality for children with JIA. Further studies are needed to understand which children with JIA may benefit from SCD, how the diet affects the immune system, and how long-lasting any effects are.