Recent studies have shown a critical role of the gastrointestinal microbiome in brain and behavior via the complex gut−microbiome−brain axis, however, the influence of the oral microbiome in neurological processes is much less studied, especially in response to the stimuli in the oral microenvironment such as smoking. Additionally, given the complex structural and functional networks in brain system, our knowledge about the relationship between microbiome and brain function in specific brain circuits is still very limited. In this pilot work, we leveraged next generation microbial sequencing with functional neuroimaging techniques to enable the delineation of microbiome-brain network links as well as their relationship to cigarette smoking. Thirty smokers and 30 age- and sex- matched non-smokers were recruited for measuring both microbial community and brain functional networks. Statistical analyses were performed to demonstrate the influence of smoking on the abundance of the constituents within the oral microbial community and functional network connectivity among brain regions as well as the associations between microbial shifts and the brain functional network connectivity alternations. Compared to non-smokers, we found a significant decrease in beta diversity (p = 6×10-3) in smokers and identified several classes (Betaproteobacteria, Spirochaetia, Synergistia, and Mollicutes) as having significant alterations in microbial abundance. Taxonomic analyses demonstrate that the microbiota with altered abundance are mainly involved in pathways related to cell processes, DNA repair, immune system, and neurotransmitters signaling. One brain functional network connectivity component was identified to have a significant difference between smokers and nonsmokers (p = 0.033), mainly including connectivity between brain default network and other task positive networks. The brain functional component was also significantly associated with some smoking related oral microbiota, suggesting a potential link between smoking-induced oral microbiome dysbiosis and brain functional connectivity, possibly through immunological and neurotransmitter signaling pathways. This work is the first attempt to link oral microbiome and brain functional networks, and provides support for future work in characterizing the role of oral microbiome in mediating smoking effects on brain activity.

Correlation between the oral microbiome and brain resting state connectivity in smokers