The Oral-Microbiome-Brain Axis and Neuropsychiatric Disorders: An Anthropological Perspective

Abstract

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.

Mental health and periodontal and peri‐implant diseases

“…Direct causal mechanisms have been proposed to explain the connection between oral microbiota, the brain, and how this relationship may influence the development of mental health disorders. The four direct causal mechanisms proposed are microbial and metabolite escape, neuroinflammation, central nervous system signaling, and response to neurohormones 200 . A common theme of these mechanisms is inflammation through a host reaction.…”

“…201 Microbial and metabolite escape Microbial species are commensal and usually have a resident niche where they are not pathogenic. However, as Bowland and Weyrich 200 suggest, owing to dysfunction, if a microbial species is able to disseminate via a bacteremia, then it or its products have the potential to cause disease. One of the possible mechanisms whereby the microbiota could contribute to neuroinflammation is via circulating endotoxins-that is, lipopolysaccharides, which are part of the outer membrane of Gram-negative bacteria-or other microbe-or pathogen-associated molecular patterns.…”

“…The four direct causal mechanisms proposed are microbial and metabolite escape, neuroinflammation, central nervous system signaling, and response to neurohormones. 200 A common theme of these mechanisms is inflammation through a host reaction. In addition, exposure to physical or psychosocial stressors at a young age or continually may result in systemic and neuro‐inflammation.…”

“… 209 Caspani et al 210 suggested three mechanisms of action: (a) direct stimulation of central nervous system receptors; (b) peripheral stimulation of neural, endocrine, and immune mediators; and (c) epigenetic regulation of histone acetylation and deoxyribonucleic acid methylation. Bowland and Weyrich, 200 in their review, presented another potential mechanism of afferent signaling via the vagus nerve, which relays signals from the gut to the central nervous system and may be able to sense gut microbial metabolites.…”

Studying ancient human oral microbiomes could yield insights into the evolutionary history of noncommunicable diseases

“…Despite these associations, there are also direct mechanisms by which the oral microbiome can contribute to systemic diseases independently of oral diseases. Three main mechanisms have been proposed for how the oral microbiome is able to impact the rest of the body: (1) the translocation of oral microbes into other regions, (2) the translocation of oral microbiome metabolites, and (3) the instigation of immunological and inflammatory modulations that have systemic effects (Hajishengallis 2015;Thomas et al 2021;Kleinstein, Nelson, and Freire 2020;Park et al 2022;Bowland and Weyrich 2022). Via these mechanisms, various NCDs have been shown to be directly caused by the oral microbiome; these interactions are described in greater detail in the following sections.…”