Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota

Abstract

Multiple sclerosis (MS) is more common in western countries with diet being a potential contributing factor. Here we show that intermittent fasting (IF) ameliorated clinical course and pathology of the MS model, experimental autoimmune encephalomyelitis (EAE). IF led to increased gut bacteria richness, enrichment of the Lactobacillaceae, Bacteroidaceae, and Prevotellaceae families and enhanced antioxidative microbial metabolic pathways. IF altered T cells in the gut with a reduction of IL-17 producing T cells and an increase in regulatory T cells. Fecal microbiome transplantation from mice on IF ameliorated EAE in immunized recipient mice on a normal diet, suggesting that IF effects are at least partially mediated by the gut flora. In a pilot clinical trial in MS patients, intermittent energy restriction altered blood adipokines and the gut flora resembling protective changes observed in mice. In conclusion, IF has potent immunomodulatory effects that are at least partially mediated by the gut microbiome.

Inhibitory milieu at the multiple sclerosis lesion site and the challenges for remyelination

“…People with MS have a relatively low abundance of the Bacteroides, Parabacteroides, Prevotella, and Lactobacillus genera and an increased abundance of Akkermansia, Blautia, Ruminococcus, and Bifidobacterium (Jangi et al, ; Opazo et al, ; Zhu et al, ). In fact, many studies have linked such dysbiosis of the gut microbiome with both adult and pediatric MS disease incidence and prognosis (Camara‐Lemarroy, Metz, & Yong, ; Castillo‐Alvarez & Marzo‐Sola, ; Cekanaviciute et al, ; Cignarella et al, ; Kirby & Ochoa‐Reparaz, ; Libbey et al, ; Mangalam & Murray, ; Nourbakhsh et al, ; Ochoa‐Reparaz, Kirby, & Kasper, ; Tankou et al, ; Tremlett, Fadrosh, Faruqi, Hart, et al, ; Tremlett, Fadrosh, Faruqi, Zhu, et al, ; Tremlett & Waubant, ). Due to the presence of organized lymphoid structures, termed Peyer's patches, within the small intestine, a great deal of focus has been put on the influence of the gut microbiome on the immune pathology in MS. For instance, a pilot study including 20 patients with RRMS in Milan examined whether high vegetable, low protein (HV/LP) diet exhibited positive effects on MS disease course compared to a classical western diet through alterations in the gut microbiota (Saresella et al, ).…”

Factors that affect the translation of dietary restriction into a longer life

“…Furthermore, in a mouse model of experimental autoimmune encephalomyelitis, intermittent fasting leads to lower demyelination and disease incidence. The transfer of the intestinal microbiome from mice that are fed intermittently to GF mice ameliorates the encephalomyelitis of mice fed a normal diet …”

“…Specifically, at the phylum level, intermittent fasting leads to a shift in the bacterial community from the phylum Bacteroidetes to the phylum Firmicutes. The intestinal microbiome of intermittently fasted mice shows an increase in bacterial diversity and an enrichment of Bacteroidaceae, Lactobacillaceae, and Prevotellaceae . These effects on the microbiome are also associated with increases in the number of goblet cells and intestinal mucus production …”

“…The transfer of the intestinal microbiome from mice that are fed intermittently to GF mice ameliorates the encephalomyelitis of mice fed a normal diet. 108 Specifically, at the phylum level, intermittent fasting leads to a shift in the bacterial community from the phylum Bacteroidetes to the phylum Firmicutes. The intestinal microbiome of intermittently fasted mice shows an increase in bacterial diversity and an enrichment of Bacteroidaceae, Lactobacillaceae, and Prevotellaceae.…”

“…The intestinal microbiome of intermittently fasted mice shows an increase in bacterial diversity and an enrichment of Bacteroidaceae, Lactobacillaceae, and Prevotellaceae. 108 These effects on the microbiome are also associated with increases in the number of goblet cells and intestinal mucus production. 109 Taken together, these findings show that DR and CR exert their positive effects on health and lifespan through various ways, through interaction with specific signaling systems of the host, and through modification of the microbiome.…”