Prolonged therapeutic fasting induces a gut microbiome fasting signature in patients with autoimmune disorders

The gut microbiome has been linked to the etiology of autoimmune diseases. As such it presents a new target for this set of difficult-to-treat disorders. One way to modulate the gut microbiome is through dietary modifications. Among these, prolonged therapeutic fasting and ketogenic diets are quickly gaining popularity as they have been shown to ameliorate symptoms of several autoimmune diseases as well as affect the gut microbiome of control populations. However, it is unknown if and how the gut microbiome in patients with autoimmune disease is responding to these interventions.Here we compare the effect of prolonged fasting on the gut microbiome in the context of two different autoimmune diseases (multiple sclerosis and type 1 diabetes mellitus) as well as against a ketogenic and a control diet.Our study suggests that prolonged fasting leads to signature modulations in the gut microbiome. We report several fasting-induced differentially abundant taxa that are shared across diseases as well as between two subsequent therapeutic fasts within individuals, with most modifications occurring directly after the fast and some remaining until the follow-up period. Furthermore, a correlation analysis of the conjointly changed genera with fasting-mediated changes of clinical parameters revealed several significant associations.The identified fasting-mediated microbiome signature can serve as a starting point to investigate whether the changes in these taxa are causally linked to the reported clinical benefits of therapeutic fasting in autoimmune diseases.