Dietary Protection Against the Visual and Motor Deficits Induced by Experimental Autoimmune Encephalomyelitis

Abstract

5-8% of the world population currently suffers from at least one autoimmune disorder. Despite multiple immune modulatory therapies for autoimmune demyelinating diseases of the CNS, these treatments are restricted to subsets of patients. To overcome these barriers, we investigated a nutritional intervention in mice undergoing experimental autoimmune encephalomyelitis (EAE). This model of autoimmune-mediated demyelination induces visual and motor pathologies similar to those experienced by patients with multiple sclerosis. Here, we report that limiting dietary carbohydrates by feeding mice a well-formulated ketogenic diet (WFKD) enriched in medium chain triglycerides, alpha-linolenic acid, and fiber protects from EAE-induced optic neuritis and motor deficits. The WFKD increased circulating ketones but did not cause weight gain while preserving visual acuity and motor function in both female and male EAE mice. Immunohistochemistry of optic nerves revealed that the WFKD preserved oligodendrocytes and reduced infiltrating T cells and macrophages. The WFKD also increased anti-inflammatory-associated omega-3 fatty acids in the plasma and reduced select cytokines in the circulation associated with inflammation and EAE pathologies. In support of ongoing clinical trials using dietary strategies to treat MS patients, these findings support that a WFKD promotes a systemic anti-inflammatory milieu that mitigates autoimmune-induced demyelinating visual and motor deficits.

Overview of diet and autoimmune demyelinating optic neuritis: a narrative review

“…The commensal microbiota and their collective metabolites are primary regulators of immune cell function, health, and autoimmunity, particularly in the context of T cell-driven autoimmunity in tissues distant from the gut, including the eye [187,188] . Dietary fiber is essential for maintaining a healthy commensal microbiota [189][190][191] and low consumption of sufficient fiber has been associated with increased FDE incidence [127] , whereas higher dietary fiber correlates with reduced motor deficits, optic neuritis, and visual acuity loss in EAE mice [117,192,193] and overall better health outcomes [128] . (4) Dietary patterns that reduce biomarkers of MS disease severity.…”

“…A recent study [171] showed that 6 months of an adapted ketogenic diet (ie, average daily intake of >160 g fat [ω6 vs ω3 ratio 2:1], <50 g carbohydrates, and average protein intake ≤100 g/day) reduced sNFL, a recognized biomarker of MS severity [194][195][196][197] . Additional clinical and animal evidence support the efficacy of ketogenic diets and other approaches (eg, fast-mimicking diets and intermittent fasting) that induce starvation responses as a common mechanism to ameliorate ADON (eg, [117] and other diseases [reviewed in [198] ]). Recent work has shown that a ketogenic diet can decrease pro-inflammatory T H 17 cells in the lamina propria, a mucosal layer of the small intestine, and modulate the gut microbiome [199] .…”

“…We have shown that a weight-stabilizing ketogenic diet enriched in medium chain triglycerides, flaxseed oil, and insoluble fiber prevents the onset of optic neuritis and motor deficits in MOG 35–55 -EAE mice. When initiated after symptom onset, this diet improved visual and motor function in both male and female mice within 4 days and effectively resolved functional deficits tested within 2 weeks [117] .…”