Immunological Impact of a Gluten-Free Dairy-Free Diet in Children With Kidney Disease: A Feasibility Study

Kidney disease affects 10% of the world population and is associated with increased mortality. Steroid-resistant nephrotic syndrome (SRNS) is a leading cause of end-stage kidney disease in children, often failing standard immunosuppression. Here, we report the results of a prospective study to investigate the immunological impact and safety of a gluten-free and dairy-free (GF/DF) diet in children with SRNS. The study was organized as a four-week summer camp implementing a strict GF/DF diet with prospective collection of blood, urine and stool in addition to whole exome sequencing WES of DNA of participants. Using flow cytometry, proteomic assays and microbiome metagenomics, we show that GF/DF diet had a major anti-inflammatory effect in all participants both at the protein and cellular level with 4-fold increase in T regulatory/T helper 17 cells ratio and the promotion of a favorable regulatory gut microbiota. Overall, GF/DF can have a significant anti-inflammatory effect in children with SRNS and further trials are warranted to investigate this potential dietary intervention in children with SRNS.

[1]  D. Gipson,et al.  Plasma Zonulin Levels in Childhood Nephrotic Syndrome , 2019, Front. Pediatr..

[2]  Xiaotian Chen,et al.  Faecalibacterium prausnitzii Produces Butyrate to Maintain Th17/Treg Balance and to Ameliorate Colorectal Colitis by Inhibiting Histone Deacetylase 1. , 2018, Inflammatory bowel diseases.

[3]  R. Parekh,et al.  Idiopathic nephrotic syndrome in children , 2018, The Lancet.

[4]  F. Emma,et al.  Immunology of idiopathic nephrotic syndrome , 2018, Pediatric Nephrology.

[5]  K. Kaneko,et al.  Gut Microbiota Dysbiosis in Children with Relapsing Idiopathic Nephrotic Syndrome , 2018, American Journal of Nephrology.

[6]  J. Bonventre,et al.  Effect of Combined Gluten-Free, Dairy-Free Diet in Children With Steroid-Resistant Nephrotic Syndrome: An Open Pilot Trial , 2018, Kidney international reports.

[7]  S. Mane,et al.  Whole Exome Sequencing of Patients with Steroid-Resistant Nephrotic Syndrome. , 2018, Clinical journal of the American Society of Nephrology : CJASN.

[8]  A. Anarat,et al.  Long-Term Outcome of Steroid-Resistant Nephrotic Syndrome in Children. , 2017, Journal of the American Society of Nephrology : JASN.

[9]  A. Fasano,et al.  Celiac Disease and Nonceliac Gluten Sensitivity: A Review , 2017, JAMA.

[10]  R. Sartor,et al.  Dietary Salt Exacerbates Experimental Colitis , 2017, The Journal of Immunology.

[11]  Xiaofeng Liao,et al.  Control of lupus nephritis by changes of gut microbiota , 2017, Microbiome.

[12]  R. Wolf,et al.  Persistent Economic Burden of the Gluten Free Diet , 2017, Nutrients.

[13]  S. Duncan,et al.  Faecalibacterium prausnitzii: from microbiology to diagnostics and prognostics , 2017, The ISME Journal.

[14]  J. Craig,et al.  Interventions for idiopathic steroid-resistant nephrotic syndrome in children. , 2016, The Cochrane database of systematic reviews.

[15]  D. Gipson,et al.  The Effect of a Gluten-Free Diet in Children With Difficult-to-Manage Nephrotic Syndrome , 2016, Pediatrics.

[16]  Wen-jie Ji,et al.  Th17/Treg Imbalance Induced by Dietary Salt Variation Indicates Inflammation of Target Organs in Humans , 2016, Scientific Reports.

[17]  Cheng-gong Yu,et al.  Faecalibacterium prausnitzii supernatant ameliorates dextran sulfate sodium induced colitis by regulating Th17 cell differentiation. , 2016, World journal of gastroenterology.

[18]  X. Zhao,et al.  Th17/Treg cell expression in children with primary nephritic syndrome and the effects of ox-LDL on Th17/Treg cells. , 2016, Genetics and molecular research : GMR.

[19]  E. Königshausen,et al.  Circulating Permeability Factors in Primary Focal Segmental Glomerulosclerosis: A Review of Proposed Candidates , 2016, BioMed research international.

[20]  Friedhelm Hildebrandt,et al.  Exploring the genetic basis of early-onset chronic kidney disease , 2016, Nature Reviews Nephrology.

[21]  Sara Omenetti,et al.  The Treg/Th17 Axis: A Dynamic Balance Regulated by the Gut Microbiome , 2015, Front. Immunol..

[22]  V. Kuchroo,et al.  Th17 Cell Pathway in Human Immunity: Lessons from Genetics and Therapeutic Interventions. , 2015, Immunity.

[23]  I. Comino,et al.  Detection of gluten immunogenic peptides in the urine of patients with coeliac disease reveals transgressions in the gluten-free diet and incomplete mucosal healing , 2015, Gut.

[24]  J. McCaffrey,et al.  The non-immunosuppressive management of childhood nephrotic syndrome , 2015, Pediatric Nephrology.

[25]  M. Wright,et al.  High salt reduces the activation of IL-4- and IL-13-stimulated macrophages. , 2015, The Journal of clinical investigation.

[26]  F. Sung,et al.  Occurrence of Common Allergic Diseases in Children with Idiopathic Nephrotic Syndrome , 2015, Journal of epidemiology.

[27]  B. Hahn,et al.  Th17 cells in inflammation and autoimmunity. , 2014, Autoimmunity reviews.

[28]  P. Miossec,et al.  Th17 and regulatory T cell balance in autoimmune and inflammatory diseases. , 2014, Autoimmunity reviews.

[29]  Björn Usadel,et al.  Trimmomatic: a flexible trimmer for Illumina sequence data , 2014, Bioinform..

[30]  Mauricio O. Carneiro,et al.  From FastQ Data to High‐Confidence Variant Calls: The Genome Analysis Toolkit Best Practices Pipeline , 2013, Current protocols in bioinformatics.

[31]  Haiping Yang,et al.  The Role of Th17/IL-17 in the Pathogenesis of Primary Nephrotic Syndrome in Children , 2013, Kidney and Blood Pressure Research.

[32]  N. Yosef,et al.  Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells , 2013, Nature.

[33]  Larry Gold,et al.  Advances in human proteomics at high scale with the SOMAscan proteomics platform. , 2012, New biotechnology.

[34]  R. Post,et al.  Putting MyPlate to work for nutrition educators. , 2012, Journal of nutrition education and behavior.

[35]  C. Esmon,et al.  Cytoprotective signaling by activated protein C requires protease-activated receptor-3 in podocytes. , 2012, Blood.

[36]  Xia Li,et al.  Th17/Treg imbalance in adult patients with minimal change nephrotic syndrome. , 2011, Clinical immunology.

[37]  M. DePristo,et al.  A framework for variation discovery and genotyping using next-generation DNA sequencing data , 2011, Nature Genetics.

[38]  Richard Durbin,et al.  Fast and accurate long-read alignment with Burrows–Wheeler transform , 2010, Bioinform..

[39]  G. Schwartz,et al.  Measurement and estimation of GFR in children and adolescents. , 2009, Clinical journal of the American Society of Nephrology : CJASN.

[40]  Xiaodong Zhao,et al.  The prevalence of Th17 cells and FOXP3 regulate T cells (Treg) in children with primary nephrotic syndrome , 2009, Pediatric Nephrology.

[41]  Y. Sanz,et al.  Effects of a gluten-free diet on gut microbiota and immune function in healthy adult human subjects , 2009, British Journal of Nutrition.

[42]  D. Fox,et al.  Th17 cells in human disease , 2008, Immunological reviews.

[43]  M. Segal,et al.  A case of unfulfilled expectations. Cytokines in idiopathic minimal lesion nephrotic syndrome , 2006, Pediatric Nephrology.

[44]  A. Bakr,et al.  Tumor necrosis factor-α production from mononuclear cells in nephrotic syndrome , 2003, Pediatric Nephrology.

[45]  Kuender D Yang,et al.  Implications of serum TNF-beta and IL-13 in the treatment response of childhood nephrotic syndrome. , 2003, Cytokine.

[46]  M. Kemper,et al.  Transmission of glomerular permeability factor from a mother to her child. , 2001, The New England journal of medicine.

[47]  A. Fasano,et al.  Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease , 2000, The Lancet.

[48]  H. Zola,et al.  Isolation of Whole Mononuclear Cells from Peripheral Blood and Cord Blood , 1996, Current protocols in immunology.

[49]  S. Swan,et al.  Circulating factor associated with increased glomerular permeability to albumin in recurrent focal segmental glomerulosclerosis. , 1996, The New England journal of medicine.

[50]  J. Egido,et al.  Increase of tumour necrosis factor α synthesis and gene expression in peripheral blood mononuclear cells of children with idiopathic nephrotic syndrome , 1994, European journal of clinical investigation.

[51]  B. Myers,et al.  Elevated Levels of Tumor Necrosis Factor-α in the Nephrotic Syndrome in Humans , 1993 .

[52]  A. Koyama,et al.  A glomerular permeability factor produced by human T cell hybridomas. , 1991, Kidney international.

[53]  G. Rostoker,et al.  Food allergy and idiopathic nephrotic syndrome. , 1989, Kidney international. Supplement.

[54]  G. Lagrue,et al.  Dietary manipulation for idiopathic nephrotic syndrome , 1989, Allergy.

[55]  J. Rapola,et al.  Long-term outcome of primary nephrotic syndrome. , 1982, Archives of disease in childhood.

[56]  J. Strauss,et al.  SEVERE STEROID-RESPONSIVE NEPHROSIS ASSOCIATED WITH HYPERSENSITIVITY , 1977, The Lancet.

[57]  K. Lemley,et al.  Effects of gluten-free, dairy-free diet on childhood nephrotic syndrome and gut microbiota , 2015, Pediatric Research.

[58]  C. Parrish,et al.  Kids and the Gluten-Free Diet , 2007 .

[59]  J. Sainte-Laudy,et al.  Basophil sensitization for food allergens in idiopathic nephrotic syndrome. , 1986, Nephron.