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In the 21st century, neuropsychiatric disorders (NPDs) are on the rise, yet the causal mechanisms behind this global epidemic remain poorly understood. A key to these unknowns may lie within the vast communities of bacteria, fungi, and viruses in the body (microbiota), which are intimately linked with health and disease. NPDs were recently shown to be connected to gut microbiota, which can communicate with and influence the brain through the Gut-Brain-Axis (GBA). Parallel studies examining oral microbiota and their connections to the brain also suggest that microbes in the mouth can similarly influence NPD outcomes. However, the mechanisms and pathways that illuminate how oral microbiota and brain communicate in NPDs remain unknown. Here, we review identified mechanisms and pathways that oral microbiota use to engage the brain, and we lay the theoretical foundation for an oral-microbiota-brain axis (OMBA). Specifically, we examine established neuroinflammatory and immune system activation responses that underpin interactions between the oral microbiota and the central nervous system (CNS), detailing four specific mechanisms: (1) microbial and metabolite escape, (2) neuroinflammation, (3) CNS signaling, and (4) response to neurohormones. We then scrutinize why including the OMBA, in addition to the GBA, is critically needed to elucidate specific causal relationships between microbial dysbiosis and observed NPD development and progression. Furthermore, we argue for comprehensive, interdisciplinary approaches that integrate lab-based microbiome research and population-level studies that examine the OMBA to improve NPDs. We specifically identify key anthropological perspectives that integrate sociocultural, epidemiological, genetic, and environmental factors that shape the oral microbiome and its interactions with NPDs. Together, future studies of the OMBA in conjunction with interdisciplinary approaches can be used to identify NPD risks and improve outcomes, as well as develop novel intervention and treatment strategies.

This study examined the relationships between hair cortisol concentrations (HCC) and sex, age, nutritional status (as determined by body condition scores, or BCS), and body mass (geometric mean calculated from morphometric measurements), as well as the potential influence of hair pigmentation (light, dark, or agouti/mixed) on HCC in dogs of the Bosawas Biosphere Reserve, Nicaragua. The dogs examined in this study live in a marginal environment where disease, malnutrition, and mortality rates are high. For fur color, HCC was significantly higher in light fur than in than dark and mixed fur (p < 0.001). In addition, BCS scores were found to have a negative effect on HCC (p < 0.001). Measures of sex and body size exhibited inconclusive effects on HCC, and when compared to adult dogs, juvenile dogs did not exhibit significantly different HCC. Repeated measures of dogs over time reveal a moderate intra-class correlation, suggesting that there are unmeasured sources of individual-level heterogeneity. These findings imply a need to account for fur color in studies of HCC in dogs, and the study suggests an overlooked relationship between cortisol and body condition scores in undernourished dogs in diverse settings.