Connecting the dots between diet, physical activity, gut microbiota and systemic lupus erythematosus

Abstract

Introduction: Systemic lupus erythematosus (SLE) is an immune-mediated disease with a diverse phenotype that mainly affects young women and is associated with high morbidity and mortality. New treatment strategies are much needed. Dysbiosis and a higher gut permeability may facilitate the translocation of microbes and their metabolites to the bloodstream, contributing to the chronic activation of the immune system seen in SLE. Objectives: Study diet, physical activity, and gut microbiota in SLE. Methods: Healthy controls (HC) and SLE patients who met the 2019 EULAR/ACR SLE criteria were included. Dietary intake was assessed by three 24-hour dietary recalls, adherence to the Mediterranean diet with PREDIMED and KIDMED questionnaires, physical activity with IPAQ questionnaire, body composition by air displacement plethysmography. The intestinal microbiota was sequenced by Next Generation Sequencing (16S rRNA), and glucagon-like peptide-1 concentrations were assessed by ELISA. Results: This cross-sectional study included 33 SLE patients (87.9% women; 67% with lupus nephritis) and 13 age and gender-matched HC. SLE patients had lower adherence to the Mediterranean diet (p=0.0222), consumed less n-3 polyunsaturated fatty acids (PUFA) (p=0.0248), a-linolenic acid (p<0.0001), eicosapentaenoic acid (p=0.0077), and fiber (p<0.0001), and had a higher n-6/n-3 PUFA ratio than HC (p=0.0042). SLE patients had lower physical activity (p=0.0302), higher sitting time (p=0.0479), and fat mass (p=0.0118). SLE patients had a decreased gut microbiota a-diversity (p=0.028), which was associated with the Mediterranean diet (p=0.014), and with eicosapentaenoic and docosahexaenoic acid, two n-3 PUFA (p=0.0127). Finally, the Rikenellaceae bacterial family was increased in patients with lupus nephritis. Conclusion: In this cohort of SLE patients, there was a low adherence to the Mediterranean diet, a low intake of several macro and micronutrients, low physical activity, high fat mass, and gut dysbiosis. Together, these findings support the hypothesis that rebalancing the gut microbiota could be a promising therapeutic target in SLE.