Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) and both environmental factors and genetic background affect its development. Due to the fact that MS is more prevalent in western countries, scientists have started to hypothesize that dietary habits could play an important role in MS risk. However, solid scientific data regarding the relationship between nutrition and MS pathogenesis is lacking.
A new study, led by Dr. Laura Piccio from the Washington University School of Medicine in St. Louis (Missouri, USA), has found that intermittent fasting may ameliorate autoimmune responses in multiple sclerosis through the gut microbiome.
The researchers previously showed that fasting can reduce MS-like symptoms in mice by inducing metabolic and physiological modifications, with an associated modulation of endogenous corticosteroids and systemic adipokines. Based on these previous findings, the researchers wanted to better explore the role of calorie restriction in the clinical course and pathology of the experimental autoimmune encephalomyelitis (EAE) model and in a small pilot trial with patients with relapsing-remitting MS.
Mice fasted every other day (intermittent fasting group; n = 10) or ate freely (control group; n = 10) for 4 weeks before receiving immunization to trigger MS-like symptoms. Both groups of mice then continued on the same diets for seven weeks.
Intermittent fasting ameliorated EAE’s clinical course, as the mice that fasted every other day were less likely to develop signs of neurological damage, including difficulty walking, limb weakness and paralysis. Fasting also led to less inflammatory cell infiltration and fewer demyelinated axons in the spinal cord, together with a reduction of interleukin (IL)-17-producing cells and an increase in regulatory T cells in the gut lamina propria. Parallel to these findings, intermittent fasting was related to decreased serum levels of leptin and increased adiponectin, corticosterone and b-hydroxybutyrate. On the whole, these results show that intermittent fasting not only ameliorated the EAE clinical course, but also its pathology and the immune response.
The researchers also wanted to elucidate whether the gut microbiota—apart from changes in hormone and adipokines levels—might mediate the effects of intermittent fasting on inflammation and the immune response. After 4 weeks, mice in the intervention group sheltered a more diverse gut microbiome when compared with the control group. Specifically, intermittent fasting led to a gut microbiota composition enrichment of the Lactobacillaceae, Bacteroidaceae and Prevotellaceae families and enhanced anti-oxidative microbial metabolic pathways. Lactobacillus species that were over-represented in the intermittent fasting mice’s fecal samples include L. johnsonii, L. reuteri, L. murinus and L. sp. ASF360. In line with these results, some Lactobacillus species have been shown to lessen EAE severity in rats.
The involvement, at least in part, of the gut microbiota in MS-like symptoms development was also supported by the fact that fecal microbiome transplantation from mice on intermittent fasting ameliorated EAE in recipient mice on a normal diet.
Based on the beneficial effects of fasting in murine EAE, the researchers conducted a small randomized controlled pilot trial to examine the effects of intermittent energy restriction in 16 patients with relapsing-remitting MS—which is the most common form of the disease—with a steroid regimen. In this pilot trial, 8 MS patients stayed on their usual Western-style diet for 15 days, while 8 MS patients underwent alternate-day fasting for 6 days (from the whole 15-week study period, patients in the intervention group adhered to the fasting diet only during the first 6 days). Intermittent energy restriction in MS patients induced changes in leptin levels and gut microbiota that were similar to what was observed in mice with EAE. Intermittent fasting led to similar changes in the relative abundance of the four main phyla Bacteroidetes, Firmicutes, Actinobacteria, and Verrucomicrobia in humans undergoing intermittent fasting when compared with mice data. Specifically, fasting led to an increased abundance of Faecalibacterium—which was strongly correlated with blood adiponectin levels—and Blautia (belonging to Clostridium XIV and XIVa) in MS patients, which are involved in butyrate production and have been reported to be reduced in MS patients.
In conclusion, these findings in murine EAE and relapsing-remitting MS patients show that intermittent fasting may have protective effects on MS symptoms that are at least partially mediated by the gut microbiome. The translational potential of intermittent fasting deserves further human studies with larger samples of patients and longer follow-up interventions.
Reference:
Cignarella F, Cantoni C, Ghezzi L, et al. Intermittent fasting confers protection in CNS autoimmunity by altering the gut microbiota. Cell Metab. 2018; 27(6):1222-35. doi: 10.1016/j.cmet.2018.05.006.
