gms | German Medical Science

Background: In Westernized nations, the incidence of autoimmune diseases such as systemic lupus erythematosus (SLE) has dramatically risen over the past few decades. Environmental influences and their interplay with genetic risk factors have been suggested as important contributors to the rapid epidemic progress. Among environmental influences, Western diet – classically high in fat and low in fibre – has been postulated as important risk. In inflammatory diseases like asthma, colitis or diabetes, beneficial effects were suggested for dietary fibre.

Methods: In SLE, the impact of dietary fibres and short-chain fatty acids remains largely unexplored and was addressed in this study using the well-established NZB/WF1 model of murine lupus.

Generally, mice were fed a low–fibre versus high-fibre diet from the age of 3 weeks and over the course of the whole experiment. Examined were disease development and underlying immunologic changes.

Results: Animals fed a low fibre diet showed increased autoantibody titres. This went along with reduced overall survival, lymphoproliferation and a tendentiously higher infiltration of the kidney by leukocytes. Interestingly, these results were also reflected in systemic immunologic changes. The distribution of the main immune cell subsets in animals fed a high fibre diet more closely resembled that of yet healthy animals. Particularly striking were reduced levels of CD4 and CD8 T cell activation in high fibre-treated animals. Interestingly, and further supporting decreased autoantibody levels was, that part of the high fibre-treated animals also displayed a reduction of CXCR5hiPD1hi follicular B-helper T cells and IFNγ production. In addition, dietary fibres are known to influence energy homeostasis and gut homeostasis. Accordingly, we observed a significant decrease in white adipose tissue and overall body weight as well as decreased intestinal leakage in high fibre-fed animals.

Conclusion: To understand the underlying molecular mechanism, we are currently examining if the observed beneficial effects are attributed to an increased fermentation of dietary fibre to short chain fatty acids (SCFA) by colonic commensal bacteria. SCFA intersect in various ways and at different sites with the immune system and mostly have anti-inflammatory effects. Apart from SCFA effects, we are exploring in how far decreased white adipose tissue and intestinal leakage in high fibre fed animals affect autoimmune pathogenesis.