Protein turnover at synapses via autophagy: implications for Parkinson's disease

Research on the human gut microbiota has bloomed in the past 2 decades as evidence of its impact on human health is accumulating. While surveys of the gut microbiota of Western/industrialized populations have generated thousands of publications, populations in developing countries have received considerably less attention. Yet, the tens of publications exploring the microbiome of these less represented populations have given a first idea of the extensive biodiversity still to be discovered and the numerous divergences compared to Western populations. Remarkably, remote populations in developing countries possess bacteria that are completely absent or rare in the gut microbiota of industrialized populations, coined as VANISH (Volatile and/or Associated Negatively with Industrialized Societies of Humans) taxa: species of the family Prevotellaceae (Prevotella) and Paraprevotellaceae (Paraprevotella), as well as bacteria from the Succinivibrionaceae family (notably Succinivibrio and Ruminobacter genera) and Spirochaetaceae (Treponema) families. We used next-generation sequencing (16S rRNA gene marker and shotgun) of the gut microbiome of a large transitioning rural Congolese population with a suspected greater homogeneity of life style to test association of these VANISH species with host health. We did not find meaningful association between VANISH taxa and health or disease parameters. We did observe a tendency for them to occur within normal moisture ranges rather than high or low moisture extremes. These conserved bacteria across populations of rural developing countries do not seem harmful from this perspective but a beneficial role is not apparent either. They were present in diseased and healthy individuals.

Despite the speculations on the benefit of the VANISH taxa, no isolate had been made available for research to test this hypothesis. Based on comparisons of different non-western cohorts, we decided to isolate a bacterium from the genus Treponema, present in the Congolese cohort presented in this thesis, as well as a Peruvian cohort for which we had viable samples in our laboratory and authorization to culture. We sequenced the genome of this new species and described the strain extensively. The isolation of this bacterium from feces shows that it can survive the passage through the gastro-intestinal tract and could therefore be involved in active interactions with host cells and other bacteria.

The newly isolated Treponema strain was tested for pathogenicity and colonization in a mice model before testing its ability to interact within this mammalian host. No sign of pathogenicity in SPF and Germ-free mice was observed in the conditions tested. Colonization potential proved much more challenging to evaluate as we could not obtain a single colonization. More research is needed to know if these bacteria can effectively interact with the intestinal immune system of their host and/or provide specific benefits.