Influence of dietary fiber and short-chain fatty acids on the pathogenesis of murine lupus

Abstract: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by production of autoantibodies against nuclear self-antigens and a broadly dysregulated immune system with severe clinical manifestations including nephritis. Generally, SLE pathogenesis results from a complex interplay between genetic and environmental factors such as infections, ‘Western lifestyle’ and nutrition. Among nutritional factors, dietary fiber and their bacterial fermentation products, short-chain fatty acids (SCFAs), have been associated with multiple, mostly beneficial effects, including amelioration of inflammatory and autoimmune diseases. Advantageous fiber- and SCFA-effects comprise reduction of adiposity, enhancement of the intestinal barrier function, shifts in the composition of intestinal microbiota as well as decreased intestinal and systemic inflammation. In this study we establish that a diet containing high concentrations of fermentable fiber (HF) ameliorates lupus pathogenesis and promotes an overall less inflamed immune phenotype in two murine models of systemic lupus. This was accompanied by an improved intestinal barrier function and decreased visceral adiposity. In turn, decreased intestinal homeostasis and increased adiposity have not only been demonstrated to be interlinked but were also shown to drive systemic inflammation and promote autoimmunity, suggesting that the HF-associated disease amelioration in lupus-prone mice may be mediated by modulation of intestinal homeostasis and reduction of adiposity. Several studies report advantageous effects in F1 offspring from mice fed dietary fiber or SCFAs during pregnancy and suckling period. In contrast to these findings, we report that neither maternal treatment with a HF-diet nor SCFAs exerts consistent effects on lupus pathogenesis or the immune status in the lupus-prone F1 offspring. Surprisingly, we observed no consistent effects of long-term oral treatment with SCFAs on lupus pathogenesis or the immune status in lupus-prone mice. Moreover, we even report deteriorating effects of SCFAs on the course of induced immune-complex nephritis and observed some inflammatory immunologic changes. In concert with a growing number of recent studies our results point out, that SCFAs may have ambivalent and even adverse effects. Most importantly, however, the findings reported in this study support the ameliorative effects of dietary fiber in autoimmunity and establish their relevance in SLE

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Universität Freiburg, Dissertation, 2022

Classification and Topics

• Keyword: Fiber in human nutrition

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2022
• Creator: Eichhorst, Alexandra
• Contributor: Chevalier, Nina ; Chevalier, Nina ; Böttler, Tobias ; Albert-Ludwigs-Universität Freiburg. Medizinische Fakultät

Further information

• DOI: 10.6094/UNIFR/225847
• URN: urn:nbn:de:bsz:25-freidok-2258478
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 25.03.2025, 1:48 PM CET