Targeted Diet Modification Reduces Multiple Sclerosis–like Disease in Adult Marmoset Monkeys from an Outbred Colony

Abstract

Experimental autoimmune encephalomyelitis (EAE) in common marmosets is a translationally relevant model of the chronic neurologic disease multiple sclerosis. Following the introduction of a new dietary supplement in our purpose-bred marmoset colony, the percentage of marmosets in which clinically evident EAE could be induced by sensitization against recombinant human myelin oligodendrocyte glycoprotein in IFA decreased from 100 to 65%. The reduced EAE susceptibility after the dietary change coincided with reduced Callitrichine herpesvirus 3 expression in the colony, an EBV-related g1-herpesvirus associated with EAE. We then investigated, in a controlled study in marmoset twins, which disease-relevant parameters were affected by the dietary change. The selected twins had been raised on the new diet for at least 12 mo prior to the study. In twin siblings reverted to the original diet 8 wk prior to EAE induction, 100% disease prevalence (eight out of eight) was restored, whereas in siblings remaining on the new diet the EAE prevalence was 75% (six out of eight). Spinal cord demyelination, a classical hallmark of the disease, was significantly lower in new-diet monkeys than in monkeys reverted to the original diet. In new-diet monkeys, the proinflammatory T cell response to recombinant human myelin oligodendrocyte glycoprotein was significantly reduced, and RNA-sequencing revealed reduced apoptosis and enhanced myelination in the brain. Systematic typing of the marmoset gut microbiota using 16S rRNA sequencing demonstrated a unique, Bifidobacteria-dominated composition, which changed after disease induction. In conclusion, targeted dietary intervention exerts positive effects on EAE-related parameters in multiple compartments of the marmoset's gutimmune-CNS axis.

Experimental autoimmune encephalomyelitis in the common marmoset: a translationally relevant model for the cause and course of multiple sclerosis

“…He proposed that health can be enhanced and aging postponed through manipulation of the gut microbiota with host-friendly bacteria present in fermented milk (Mackowiak, 2013). This is exactly what we found in the twin study (Kap et al, 2018a). We observed a positive effect of the YBS on the proportion of bifidobacteria in the marmoset stool.…”

“…For the experiment, one sibling of each twin was reverted to the old water-based supplement (WBS), starting 8 weeks prior to EAE induction, while the other sibling remained on the new yogurt-based supplement (YBS). In brief, the EAE incidence in the old WBS and new YBS groups differed, albeit not significantly (8/8 in the old diet group, 6/8 in the new diet group) (Kap et al, 2018a). In addition, we observed a significant reduction of spinal cord demyelination, markedly altered expression of genes involved in apoptosis and myelination in the brain, a marked reduction of CalHV3 expression and alteration of cellular immune parameters, which in previous studies have been implicated in the EAE pathogenesis.…”

“…The modification was rather modest, namely from a water-based to a yogurt-based formulation, which also contained the double dose of B vitamins. Nevertheless, the effects on the model were rather dramatic (Kap et al, 2018a).…”

“…The fact that nonhuman primates are bred and raised under conventional conditions implies that, similar to the situation in humans, their immune system has been trained from early life onwards by genetic diversity and the exposure to environmental pathogens, gut microbiota as well as to chronic latent infection with herpes-and polyomavirus. Of note is that the gut microbiota of marmosets is highly enriched with bifidobacteria, which most likely is an adaptation to their specific dietary habits (e.g., gum) (Kap et al, 2018b); it most closely resembles the microbiome of human neonates (own unpublished observation). The fact that marmosets are naturally infected with βand γ -herpesviruses is also particularly important; these viruses closely resemble those infecting humans (Nigida et al, 1979;Rivailler et al, 2002).…”

Variation in the Gut Microbiota of Common Marmosets: Differences with Colony of Origin and Integration

“…Recent attention to the variation in husbandry practices has underscored the relevance of such variation in research reproducibility. 8,9 Strikingly, one research group found a 25% reduction in clinically evident recombinant protein-induced experimental autoimmune encephalomyelitis (EAE) in common marmosets fed a yoghurt-based supplemental diet that differed from the standard colony enrichment; the primary diet for both groups was the same.…”