The effect of treatment with the helminth product Tuftsin-phosphorylcholine (TPC) on the microbiome of mice with active lupus

The hygiene hypothesis claims that lack of exposure to microorganisms in developed countries, correlates with increased incidence of autoimmune diseases. It was also found that helminths are able to modulate the immune response in hosts in order to survive. Consequently, several successful trials using helminths as a treatment for autoimmune diseases have been reported. The helminth derivative, phosphorylcholine (PC), was demonstrated to have immunomodulatory properties. We have recently shown in a murine model that when a conjugate of Tuftsin and PC, termed TPC, is prophylactically administered before the onset of glomerulonephritis, it attenuates the development of systemic lupus erythematosus (SLE). The current study aimed to examine the effect of TPC on the gut microbiome in a mouse model of lupus. TPC treatment altered the gut composition in the mice with active lupus, in correlation with a significant decrease in glomerulonephritis, followed by an increased level of anti-inflammatory IL-10, decreased levels of pro-inflammatory mediators, as well as expansion of the T regulatory cell population. Importantly, we found that TPC treatment altered the microbiome composition in the mouse gut, in correlation with a significant decrease in protein secretion and improved disease parameters. The major effect of TPC treatment on the genera in the gut microbiome included increased abundance of Odoribacter and decreased abundance of Akkermansia. Overall, our results suggest involvement of the microbiome in the immunomodulation of glomerulonephritis in lupus mice