Longitudinal Microbiome Samples from Alcohol Mice with EAE

Alcohol is a widely consumed dietary component by patients with autoimmune neuroinflammatory diseases, but current evidence on the effects of alcohol in these conditions is confounding. Epidemiological studies suggest moderate consumption of alcohol may be protective in some autoimmune diseases; however, this correlation has not been carefully investigated. Here, we report the first controlled investigation to characterize the effects of moderate-dose alcohol in a model system of autoimmune neuroinflammation, experimental autoimmune encephalomyelitis (EAE). Male and female C57BL/6J mice were fed a 2.6% alcohol or isocaloric diet for three weeks prior to MOG35-55 EAE induction. Surprisingly, alcohol-fed males experienced significantly greater disease remission compared to alcohol-fed females and control-fed counterparts. We observed a male-specific decrease in microglial density in cervical and thoracic spinal cord in late stage disease. In the gut, alcohol diet resulted in several sex-specific alterations in key microbiota known for their regulatory immune roles, including Turicibacter, Akkermansia, Prevotella, and Clostridium. Using a correlation network modeling approach, we identified unique bacterial modules that are significantly enriched in response to treatment and sex, comprised of Clostridial taxa and several Firmicutes known to be protective in EAE. Together, these data demonstrate the potential of alcohol to significantly affect the course of autoimmunity differentially in males and females via effects on gut bacterial networks and supports further need to evaluate dose and sex-specific alcohol effects in MS and other autoimmune neuroinflammatory conditions.