Front Immunol. 2021 Jun 2;12:624821. doi: 10.3389/fimmu.2021.624821. eCollection 2021.

María José Pérez-Sáez ^1 2, Audrey Uffing ¹, Juliette Leon ¹, Naoka Murakami ¹, Andreia Watanabe ³, Thiago J Borges ^1 4, Venkata S Sabbisetti ¹, Pamela Cureton ⁵, Victoria Kenyon ⁵, Leigh Keating ⁶, Karen Yee ⁷, Carla Aline Fernandes Satiro ⁸, Gloria Serena ⁵, Friedhelm Hildebrandt ⁹, Cristian V Riella ¹⁰, Towia A Libermann ¹¹, Minxian Wang ¹², Julio Pascual ², Joseph V Bonventre ¹, Paolo Cravedil ¹³, Alessio Fasano ⁵, Leonardo V Riella

Author information

• ¹Renal Division, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, United States.
• ²Servicio de Nefrología, Hospital del Mar, Barcelona, Spain.
• ³Department of Pediatrics, Pediatric Nephrology Unit, Instituto da Criança, Hospital das Clínicas - University of São Paulo Medical School (USP), São Paulo, Brazil.
• ⁴Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA, United States.
• ⁵Center for Celiac Research and Treatment, Massachusetts General Hospital for Children, Harvard Medical School, Boston, MA, United States.
• ⁶Experimental Therapeutics/Interventional Trials Center, Boston Children's Hospital, Boston, MA, United States.
• ⁷Center for Clinical Investigation, Brigham & Women's Hospital, Boston, MA, United States.
• ⁸Division of Nutrition, Instituto da Criança, Hospital das Clínicas - University of Sao Paulo Medical School, Sao Paulo, Brazil.
• ⁹Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States.
• ¹⁰Renal Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
• ¹¹Beth Israel Deaconess Medical Center Genomics, Proteomics, Bioinformatics and Systems Biology Center, Division of Interdisciplinary Medicine and Biotechnology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
• ¹²Medical and Population Genetics Program, Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, United States.
• ¹³Renal Division, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
• ¹⁴Division of Nephrology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Abstract

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.