Gut microbiome signature of Viliuisk encephalomyelitis in Yakuts includes an increase in microbes linked to lean body mass and eating behaviour

Abstract

Background: Viliuisk encephalomyelitis (VE) is a rare endemic neurodegenerative disease occurring in the Yakut population of Northeastern Siberia. The main clinical features of VE are spasticity, dysarthria, dementia, central paresis and paralysis, and cortical atrophy observed via MRI. Many hypotheses have been proposed regarding its etiology, including infectious agents, genetics, environmental factors, and immunopathology. Each of these hypotheses has been supported to some extent by epidemiological and experimental data. Nevertheless, none of them has been decisively proven. Gut microbiome is one of the factors that might be involved in VE pathogenesis.

Results: Here we performed a pilot survey of the stool microbiomes of Yakut subjects with VE (n = 6) and without VE (n = 11). 16S rRNA sequencing showed that in comparison with the control group, the Yakuts with VE had increased proportions of Methanobrevibacter and Christensenella, which are reported to be linked to body mass index, metabolism, dietary habits and potentially to neurodegenerative disorders. The identified associations suggest that the microbiome may be involved in VE. Overall, the Yakut microbiome was quite specific in comparison with other populations, such as metropolitan Russians and native inhabitants of the Canadian Arctic.

Conclusions: Describing the gut microbiome of indigenous human populations will help to elucidate the impact of dietary and environmental factors on microbial community structure and identify risks linked to the lifestyles of such groups as well as endemic diseases.

Keywords: 16S rRNA sequencing; Gut microbiome; Methanobrevibacter; Microbiome-gut-brain axis; Viliuisk encephalomyelitis; Yakuts.

Fig. 1

Gut community structure of Yakuts. Heatmap of the relative abundance of major microbial genera in the Yakut gut microbiome (snapshot of an interactive visualisation in the Knomics-Biota online system). The two subplots correspond to control subjects (n = 11) and Viliuisk encephalomyelitis patients (n = 6). The bar plots on the top right show the levels of the ten most-abundant taxa averaged across all subjects

Fig. 2

Cladogram highlighting differences in the abundance of microbial taxa in Yakuts without Viliuisk encephalomyelitis (n = 11) and metropolitan Russians (n = 101; external data comparison). The analysis was performed using a generalised linear model (GLM); significance threshold: FDR-adjusted p < 0.05. Notation “g__u(f__Coriobacteriaceae)” refers to “one or more unclassified genera from Coriobacteriaceae family” and so on

Fig. 3

Major microbial phyla compared in abundance between VE-free Yakuts (n = 11) and Inuits (n = 22). The phyla significantly differentially abundant in Yakuts were: increased—Firmicutes and Actinobacteria; decreased—Proteobacteria and Bacteroidetes (GLM, FDR-adjusted p < 0.05)

Fig. 4

Microbes significantly linked to Viliuisk encephalomyelitis according to the selbal method. a The taxa that were included in three most frequent balances during cross-validation procedure. For each taxon, the percent of times it was included in balances during cross-validation is shown. b The relationship between the balance selected for the full dataset and the outcome (VE status)