Effects of prebiotics and probiotics against autoimmune lupus disease

Autoimmune diseases such as systemic lupus erymathosus (SLE), multiple sclerosis and psoriasis affect 7% of the population in developed countries. Recent studies suggest that the gut microbiota is involved in the development of autoimmune diseases but the underlying mechanism remains unclear. Our previous studies showed that polysaccharides derived from medicinal fungi such as Ganoderma lucidum and Ophiocordyceps sinensis produce various health benefits in mice. For instance, high-molecular weight polysaccharides isolated from Hirsutella sinensis reduced obesity, fat accumulation, inflammation, insulin resistance and fatty liver disease in mice fed a high-fat diet. These effects were mediated by the gut microbiota as fecal microbiota transplantation from high-fat diet-fed mice treated with H. sinensis polysaccharides reduced signs of obesity, inflammation, diabetes and liver disease in high-fat diet-fed mice. Treatment with H. sinensis polysaccharides modulated the composition of the gut microbiota, especially by increasing the level of the commensal bacterium Parabacteroides goldsteinii. The fungal polysaccharides reduced inflammation by inducing the expression of intestinal tight junction proteins and the expansion of regulatory T cells in the intestinal mucosa of mice. Moreover, P. goldsteinii produced anti-obesity, anti-inflammatory and anti-diabetic effects when given orally to high-fat-diet-fed mice, suggesting that this bacterium may represent novel probiotics. In this project, we plan to continue our previous work supported by grants MOST105-2320-B-182-032-MY3, MOST105-2320-B-030-004, MOST103-2321-B-182-014-MY3 and MOST107-3017-F-182-001 to examine in detail the role of the gut microbiota in the pathogenesis of autoimmune diseases. The questions that we will address include: (1) whether polysaccharides derived from the medicinal fungus H. sinensis can reduce the severity of SLE symptoms in a murine model of imiquimod-induced lupus; (2) whether the probiotic P. goldsteinii can alleviate the symptoms of SLE in the imiquimod-induced lupus mouse model; and (3) whether the effects produced by H. sinensis polysaccharides are mediated by the gut microbiota, which can be confirmed by using fecal microbiota transplantation. Moreover, we will examine the mechanisms of action of H. sinensis polysaccharides, P. goldsteinii and fecal microbiota transplantation against SLE.The specific aims of the project are as follows:Aim 1: Determine the effects of H. sinensis polysaccharides used as prebiotics in a mouse model of imiquimod-induced SLE.Aim 2: Determine the effects of P. goldsteinii used as probiotics against SLE in the mouse model of imiquimod-induced SLE.Aim 3: Determine whether H. sinensis polysaccharides produce anti-lupus activities by modulating the gut microbiota in SLE based on the use of fecal microbiota transplantation from polysaccharide-treated mice.Our study will examine the involvement of the gut microbiota in the development of lupus autoimmune disease. Notably, our project has clear clinical implications for the treatment of autoimmune diseases since H. sinensis polysaccharides, P. goldsteinii probiotics and fecal transplantation are readily available and may reduce disease symptoms and improve quality of life in human patients affected by these conditions.

Project ID:PA10903-0005
External Project ID:MOST109-2311-B182-001-MY2