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Human gut derived Anaerotruncus colihominis ameliorates experimental autoimmune encephalomyelitis

By Paola Bianchimano, Graham J Britton, david Wallach, Emma Smith, Laura Cox, Shirong Liu, Howard Weiner, Jeremiah J Faith, Jose C. Clemente, Stephanie Tankou

Posted 10 Nov 2021
bioRxiv DOI: 10.1101/2021.11.10.468120

The gut microbiome plays an important role in autoimmunity including multiple sclerosis and its mouse model called experimental autoimmune encephalomyelitis (EAE). The gut-brain axis refers to the complex interactions between the gut microbiota and the nervous and immune systems linking brain and gut functions. Prior studies have demonstrated that the multiple sclerosis gut microbiota can contribute to disease hence making it a potential therapeutic target. Other studies have reported that long-term antibiotic therapy in multiple sclerosis patients reduces relapse rate and gadolinium enhancing lesions as well as improves measures of disability. In addition, antibiotic treatment has been shown to ameliorate disease in the EAE mouse model of multiple sclerosis. Yet, to this date, the mechanisms mediating these antibiotics effects are not understood. Furthermore, there is no consensus on the gut derived bacterial strains that drive neuroinflammation in multiple sclerosis. Hence, it remains unclear how the gut microbiota can be targeted for therapeutic purposes in multiple sclerosis patients. Here we characterized the gut microbiome of untreated and vancomycin treated EAE mice over time to identify bacteria with neuroimmunomodulatory potential. We observed alterations in the gut microbiota composition following EAE induction. We found that vancomycin treatment ameliorates EAE and that this protective effect is mediated via the microbiota. Notably, we observed increase abundance of bacteria known to be strong inducers of regulatory T cells including members of Clostridium clusters XIVa and XVIII in vancomycin-treated mice during the presymptomatic phase of EAE as well as at disease peak. We identified 50 bacterial taxa that correlate with EAE severity. Interestingly, several of these taxa exist in the human gut and some of them have been implicated in multiple sclerosis including Anaerotruncus colihominis which had a positive correlation with disease severity. Unexpectedly, we found that Anaerotruncus colihominis ameliorates EAE and this is associated with induction of ROR{gamma}t+ regulatory T cells in the mesenteric lymph nodes. Together, our results identify vancomycin as a potent modulator of the gut-brain axis by promoting the proliferation of bacterial species that induce regulatory T cells. In addition, our findings reveal 50 gut commensals as regulator of the gut-brain axis that can be used to further characterize pathogenic and beneficial host-microbiota interactions in multiple sclerosis patients. Our findings suggest that elevated Anaerotruncus colihominis in multiple sclerosis patients may represent a protective mechanism associated with recovery from the disease.

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