A pilot study of possible anti-inflammatory effects of the specific carbohydrate diet in children with juvenile idiopathic arthritis

Lillemor Berntson, Lillemor Berntson

Abstract

Background: To explore possible anti-inflammatory effects of the specific carbohydrate diet in children with juvenile idiopathic arthritis. This diet has shown anti-inflammatory effect in children with inflammatory bowel disease.

Methods: Twenty-two patients with juvenile idiopathic arthritis (age 6.3-17.3 years), with ≤2 inflamed joints and an erythrocyte sedimentation rate < 30 mm/h, were included in this explorative study. Fifteen children completing four weeks on the diet were evaluated. A dietician introduced parents and children to the diet, and two follow-ups were performed during the intervention. Conventional laboratory tests and multiplex analyses of 92 inflammatory proteins were used. Short-chain fatty acids in faecal samples were examined.

Results: The diet significantly decreased morning stiffness (p = 0.003) and pain (p = 0.048). Physical function, assessed through the child health assessment questionnaire, improved (p = 0.022). Arthritis improved in five of the seven children with arthritis; in those seven, multiplex analyses showed a significant decrease in nine inflammatory proteins, including TNF-alpha (p = 0.028), after four weeks. Faecal butyrate, analysed in all 15 participants, increased significantly (p = 0.020).

Conclusion: The specific carbohydrate diet may have significant positive effects on arthritis in children with juvenile idiopathic arthritis, but further studies are needed.

Clinical trials identifier: NCT04205500 , 2019/12/17, retrospectively registered. URL: https://register.clinicaltrials.gov.

Keywords: Arthritis; Diet therapy; Juvenile idiopathic; Pilot study.

Conflict of interest statement

The author declares no conflicts of interest.

Figures

Fig. 1
Fig. 1
ad Levels of pain on visual analogue scale (0–100 mm) (a); Morning stiffness (minutes) (b); Child health assessment questionnaire, CHAQ (0–3) (c); Concentration of butyrate (mg/g) in faecal samples (d). All at inclusion and after two and four weeks of specific carbohydrate diet. *Wilcoxon matched-pair signed rank analysis comparing levels at inclusion with levels after four weeks of specific carbohydrate diet

References

    1. Berntson L, Andersson Gare B, Fasth A, Herlin T, Kristinsson J, Lahdenne P, et al. Incidence of juvenile idiopathic arthritis in the Nordic countries. A population based study with special reference to the validity of the ILAR and EULAR criteria. J Rheumatol. 2003;30(10):2275–2282.
    1. Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, He X, Maldonado-Cocco J, Orozco-Alcala J, Prieur AM, Suarez-Almazor ME, Woo P, International League of Associations for Rheumatology International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004;31(2):390–392.
    1. van Loosdregt J, van Wijk F, Prakken B, Vastert B. Update on research and clinical translation on specific clinical areas from biology to bedside: unpacking the mysteries of juvenile idiopathic arthritis pathogenesis. Best Pract Res Clin Rheumatol. 2017;31(4):460–475. doi: 10.1016/j.berh.2018.02.003.
    1. Ramanathan K, Glaser A, Lythgoe H, Ong J, Beresford MW, Midgley A, Wright HL. Neutrophil activation signature in juvenile idiopathic arthritis indicates the presence of low-density granulocytes. Rheumatology (Oxford) 2018;57(3):488–498. doi: 10.1093/rheumatology/kex441.
    1. Hinks A, Cobb J, Marion MC, Prahalad S, Sudman M, Bowes J, et al. Dense genotyping of immune-related disease regions identifies 14 new susceptibility loci for juvenile idiopathic arthritis. Nat Genet. 2013;45(6):664–669. doi: 10.1038/ng.2614.
    1. Arvonen M, Virta LJ, Pokka T, Kroger L, Vahasalo P. Repeated exposure to antibiotics in infancy: a predisposing factor for juvenile idiopathic arthritis or a sign of this group's greater susceptibility to infections? J Rheumatol. 2015;42(3):521–526. doi: 10.3899/jrheum.140348.
    1. Kindgren E, Fredrikson M, Ludvigsson J. Early feeding and risk of juvenile idiopathic arthritis: a case control study in a prospective birth cohort. Pediatr Rheumatol Online J. 2017;15(1):46. doi: 10.1186/s12969-017-0175-z.
    1. Kristensen K, Henriksen L. Cesarean section and disease associated with immune function. J Allergy Clin Immunol. 2016;137(2):587–590. doi: 10.1016/j.jaci.2015.07.040.
    1. Picco P, Gattorno M, Marchese N, Vignola S, Sormani MP, Barabino A, Buoncompagni A. Increased gut permeability in juvenile chronic arthritides. A multivariate analysis of the diagnostic parameters. Clin Exp Rheumatol. 2000;18(6):773–778.
    1. Arvonen M, Berntson L, Pokka T, Karttunen TJ, Vahasalo P, Stoll ML. Gut microbiota-host interactions and juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2016;14(1):44. doi: 10.1186/s12969-016-0104-6.
    1. Verwoerd A, Ter Haar NM, de Roock S, Vastert SJ, Bogaert D. The human microbiome and juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2016;14(1):55. doi: 10.1186/s12969-016-0114-4.
    1. van Dijkhuizen EHP, Del Chierico F, Malattia C, Russo A, Pires Marafon D, Ter Haar NM, et al. Microbiome analytics of the gut microbiota in patients with juvenile idiopathic arthritis: a longitudinal observational cohort study. Arthritis Rheumatol. 2019;71(6):1000–1010. doi: 10.1002/art.40827.
    1. Tejesvi MV, Arvonen M, Kangas SM, Keskitalo PL, Pirttila AM, Karttunen TJ, et al. Faecal microbiome in new-onset juvenile idiopathic arthritis. Eur J Clin Microbiol Infect Dis. 2016;35(3):363–370. doi: 10.1007/s10096-015-2548-x.
    1. Di Paola M, Cavalieri D, Albanese D, Sordo M, Pindo M, Donati C, et al. Alteration of fecal microbiota profiles in juvenile idiopathic arthritis. associations with HLA-B27 Allele and disease status. Front Microbiol. 2016;7:1703. doi: 10.3389/fmicb.2016.01703.
    1. Stoll ML, Kumar R, Morrow CD, Lefkowitz EJ, Cui X, Genin A, Cron RQ, Elson CO. Altered microbiota associated with abnormal humoral immune responses to commensal organisms in enthesitis-related arthritis. Arthritis Res Ther. 2014;16(6):486. doi: 10.1186/s13075-014-0486-0.
    1. Kamada N, Seo SU, Chen GY, Nunez G. Role of the gut microbiota in immunity and inflammatory disease. Nat Rev Immunol. 2013;13(5):321–335. doi: 10.1038/nri3430.
    1. Bouskra D, Brezillon C, Berard M, Werts C, Varona R, Boneca IG, et al. Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis. Nature. 2008;456(7221):507–510. doi: 10.1038/nature07450.
    1. Ivanov II, Honda K. Intestinal commensal microbes as immune modulators. Cell Host Microbe. 2012;12(4):496–508. doi: 10.1016/j.chom.2012.09.009.
    1. Furusawa Y, Obata Y, Fukuda S, Endo TA, Nakato G, Takahashi D, Nakanishi Y, Uetake C, Kato K, Kato T, Takahashi M, Fukuda NN, Murakami S, Miyauchi E, Hino S, Atarashi K, Onawa S, Fujimura Y, Lockett T, Clarke JM, Topping DL, Tomita M, Hori S, Ohara O, Morita T, Koseki H, Kikuchi J, Honda K, Hase K, Ohno H. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. 2013;504(7480):446–450. doi: 10.1038/nature12721.
    1. Chassaing B, Koren O, Goodrich JK, Poole AC, Srinivasan S, Ley RE, Gewirtz AT. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature. 2015;519(7541):92–96. doi: 10.1038/nature14232.
    1. Suskind DL, Cohen SA, Brittnacher MJ, Wahbeh G, Lee D, Shaffer ML, Braly K, Hayden HS, Klein J, Gold B, Giefer M, Stallworth A, Miller SI. Clinical and fecal microbial changes with diet therapy in active inflammatory bowel disease. J Clin Gastroenterol. 2018;52(2):155–163. doi: 10.1097/MCG.0000000000000772.
    1. Burgis JC, Nguyen K, Park KT, Cox K. Response to strict and liberalized specific carbohydrate diet in pediatric Crohn’s disease. World J Gastroenterol. 2016;22(6):2111–2117. doi: 10.3748/wjg.v22.i6.2111.
    1. Wahbeh GT, Ward BT, Lee DY, Giefer MJ, Suskind DL. Lack of mucosal healing from modified specific carbohydrate diet in pediatric patients with Crohn disease. J Pediatr Gastroenterol Nutr. 2017;65(3):289–292. doi: 10.1097/MPG.0000000000001619.
    1. Shepherd J, Cooper K, Harris P, Picot J, Rose M. The clinical effectiveness and cost-effectiveness of abatacept, adalimumab, etanercept and tocilizumab for treating juvenile idiopathic arthritis: a systematic review and economic evaluation. Health Technol Assess. 2016;20(34):1–222. doi: 10.3310/hta20340.
    1. Glerup M, Rypdal V, Arnstad ED, Ekelund M, Peltoniemi S, Aalto K, et al. Long-term outcomes in juvenile idiopathic arthritis: 18 years of follow-up in the population-based Nordic juvenile idiopathic arthritis (JIA) cohort. Arthritis Care Res (Hoboken). 2019.
    1. Wallace CA, Giannini EH, Huang B, Itert L, Ruperto N. American College of Rheumatology provisional criteria for defining clinical inactive disease in select categories of juvenile idiopathic arthritis. Arthritis Care Res (Hoboken) 2011;63(7):929–936. doi: 10.1002/acr.20497.
    1. Singh G, Athreya BH, Fries JF, Goldsmith DP. Measurement of health status in children with juvenile rheumatoid arthritis. Arthritis Rheum. 1994;37(12):1761–1769. doi: 10.1002/art.1780371209.
    1. Consolaro A, Giancane G, Schiappapietra B, Davi S, Calandra S, Lanni S, et al. Clinical outcome measures in juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2016;14(1):23. doi: 10.1186/s12969-016-0085-5.
    1. Assarsson E, Lundberg M, Holmquist G, Bjorkesten J, Thorsen SB, Ekman D, et al. Homogenous 96-plex PEA immunoassay exhibiting high sensitivity, specificity, and excellent scalability. PLoS One. 2014;9(4):e95192. doi: 10.1371/journal.pone.0095192.
    1. Barratt MJ, Lebrilla C, Shapiro HY, Gordon JI. The gut microbiota, food science, and human nutrition: a timely marriage. Cell Host Microbe. 2017;22(2):134–141. doi: 10.1016/j.chom.2017.07.006.
    1. An Q, Yan W, Zhao Y, Yu K. Enhanced neutrophil autophagy and increased concentrations of IL-6, IL-8, IL-10 and MCP-1 in rheumatoid arthritis. Int Immunopharmacol. 2018;65:119–128. doi: 10.1016/j.intimp.2018.09.011.
    1. Liou LB, Tsai WP, Chang CJ, Chao WJ, Chen MH. Blood monocyte chemotactic protein-1 (MCP-1) and adapted disease activity Score28-MCP-1: favorable indicators for rheumatoid arthritis activity. PLoS One. 2013;8(1):e55346. doi: 10.1371/journal.pone.0055346.
    1. Koh A, De Vadder F, Kovatcheva-Datchary P, Backhed F. From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell. 2016;165(6):1332–1345. doi: 10.1016/j.cell.2016.05.041.
    1. Rosser EC, Piper CJM, Matei DE, Blair PA, Rendeiro AF, Orford M, Alber DG, Krausgruber T, Catalan D, Klein N, Manson JJ, Drozdov I, Bock C, Wedderburn LR, Eaton S, Mauri C. Microbiota-derived metabolites suppress arthritis by amplifying aryl-hydrocarbon receptor activation in regulatory B cells. Cell Metab. 2020;31(4):837–851. doi: 10.1016/j.cmet.2020.03.003.
    1. Desai MS, Seekatz AM, Koropatkin NM, Kamada N, Hickey CA, Wolter M, Pudlo NA, Kitamoto S, Terrapon N, Muller A, Young VB, Henrissat B, Wilmes P, Stappenbeck TS, Núñez G, Martens EC. A dietary Fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell. 2016;167(5):1339–1353. doi: 10.1016/j.cell.2016.10.043.
    1. Snelson M, Coughlan MT. Dietary advanced glycation end products: digestion, metabolism and modulation of gut microbial ecology. Nutrients. 2019;11(2).
    1. DeChristopher LR, Uribarri J, Tucker KL. Intake of high-fructose corn syrup sweetened soft drinks, fruit drinks and apple juice is associated with prevalent arthritis in US adults, aged 20-30 years. Nutr Diabetes. 2016;6(3):e199. doi: 10.1038/nutd.2016.7.

Source: PubMed

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