Low Dietary Fiber Intake Links Development of Obesity and Lupus Pathogenesis

Abstract

Changed dietary habits in Western countries such as reduced fiber intake represent an important lifestyle factor contributing to the increase in inflammatory immune-mediated diseases. The mode of action of beneficial fiber effects is not fully elucidated, but short-chain fatty acids (SCFA) and gut microbiota have been implicated. The aim of this study was to explore the impact of dietary fiber on lupus pathology and to understand underlying mechanisms. Here, we show that in lupus-prone NZB/WF1 mice low fiber intake deteriorates disease progression reflected in accelerated mortality, autoantibody production and immune dysregulation. In contrast to our original assumption, microbiota suppression by antibiotics or direct SCFA feeding did not influence the course of lupus-like disease. Mechanistically, our data rather indicate that in low fiber-fed mice, an increase in white adipose tissue mass, fat-inflammation and a disrupted intestinal homeostasis go along with systemic, low-grade inflammation driving autoimmunity. The links between obesity, intestinal leakage and low-grade inflammation were confirmed in human samples, while adaptive immune activation predominantly correlated with lupus activity. We further propose that an accelerated gastro-intestinal passage along with energy dilution underlies fiber-mediated weight regulation. Thus, our data highlight the often-overlooked effects of dietary fiber on energy homeostasis and obesity prevention. Further, they provide insight into how intricately the pathologies of inflammatory immune-mediated conditions, such as obesity and autoimmunity, might be interlinked, possibly sharing common pathways.