Abstract
Recent studies have shown a critical role for the gastrointestinal microbiome in brain and behavior via a 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 functions on specific brain circuits is still very limited. In this pilot work, we leverage next generation microbial sequencing with functional MRI techniques to enable the delineation of microbiome-brain network links as well as their relations 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 taxonomy and abundance of the constituents within the oral microbial community, brain functional network connectivity, and associations between microbial shifts and the brain signaling network. Among smokers, we found significant decrease in beta diversity (p = 6×10−3) and identified several classes (Betaproteobacteria, Spirochaetia, Synergistia, and Mollicutes) as having significant alterations in microbial abundance. Metagenomic 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 with marginal difference between smokers and nonsmokers (p = 0.033) consists of connectivity between default network and other task-positive networks (i.e., executive control network). This brain functional component was also significantly associated with some smoking- and immune- related oral microbiota, suggesting potential influence of smoking-induced oral microbiome dysbiosis in regulating brain functional connectivity, possibly through immunological or neurotransmitter signaling pathways. This work is the first attempt to link oral microbiome and brain functional networks, and provides the support for future work in characterizing the role of oral microbiome in mediating smoking effects on brain activity.