Mouth Brain Axis

This post is taking a “devil’s advocate” look the Sansores-España review [1]and using the ideas put forth as a strategy for further review of the literature. These authors proposed three ways of the oral microbiome connecting with the CNS.

Blood Brain Barrier Breakdown

Sansores-España et al make a case for P gingivalis entering the blood streaqm and establishing itself in a atheroma. Gingipains, intima degrading proteases, were also mentioned. Inflammatory processes soon follow. [1]

A related review focused insterad on Porphyromonas gingivalis outer membrane vesicles. [2] Cardiovascular disease, diabetes mellitis, and rheumatoid arthritis were listed as the major systemic diseases. A very brief mention was given of NAFLD. This review also mentioned small-molecule inhibitors against gingipains, blocking Ab1–42 production, reduced neuroinflammation in the hippocampus.

Oral Cavity Innervation

These are some images from an Internet search

The Sansores-España review focuses a lot on the microorganisms growing on the surface of the teeth near the gum line. These images that other cranial nerve innervate the oral cavity. [1]

Bacteria migration through trigeminal nerve endings

Sansores-España argue that since the Lyme Disease bacterium Borrelia burgdorferican enter the brain via peripheral nerves in an experimental animal and because T. denticola has been detected trigeminal ganglion, the pontine nucleus of the trigeminal nerve, and hippocampus in Alzheimer’s Disease patient and in mice with endodontic lesions, trigeminal nerve entry into the brain is plausible. [1]

There are other cranial nerves that innervate the oral cavity.

Listeria monocytogenes can be associated with rhombencephalitis. “Three females (41, 64 and 70 years) with culture proven L. monocytogenes bacteremia and rhombencephalitis were investigated in the period of 2014-16. T2-weighted and contrast-enhanced T1-weighted MRI revealed a cerebellopontine abscess in all three patients, including the involvement of the trigeminal nerve root. In two patients, MRI also revealed selective contrast enhancement of the sensory trigeminal tract in the pons and medulla oblongata. Prior to any other neurological symptoms, two patients complained of hypoesthesia and a tingling sensation in the ipsilateral half of the face, consistent with sensory trigeminal nerve dysfunction on that side. In addition, we identified another 120 cases of Listeria rhombencephalitis following a systematic review. Cranial nerves VII, V, IX, and X, respectively, medulla oblongata, cerebellum and pons, were the most frequently involved brain structures. The present clinical and radiological findings corroborate earlier data from animal experiments, indicating that L. monocytogenes may be capable of retrograde intra-axonal migration along the cranial nerves. We suggest that in a subset of patients with rhombencephalitis L. monocytogenes enters the cerebellopontine angle through the trigeminal nerve, invading the brainstem via the sensory trigeminal nuclei.”

Does Listeria monocytogenes even proliferate in the oral cavity? If the trigeminal nerve is a route of entry, what determines the course of travel? What about other cranial nerves and other bacteria?

Bacteria migration through the lymphatic system

This image is being presented because it shows the lymph nodes of the oral cavity. arrows indicate the direction of flow.

Sansores-España et al don’t seem to be much stock in the lymphatic system being a route of oral bacteria to the brain. It is worth noting that this route is much shorter than the gut to the brain route.

This image describes lymph drainage from the CSF and how bacteria may migrate from the oral cavitgy.


  1. Sansores-España LD, Melgar-Rodríguez S, Olivares-Sagredo K, Cafferata EA, Martínez-Aguilar VM, Vernal R, Paula-Lima AC, Díaz-Zúñiga J. Oral-Gut-Brain Axis in Experimental Models of Periodontitis: Associating Gut Dysbiosis With Neurodegenerative Diseases ng. 2021 Dec 10;2:781582 PMC free article
  2. Zhang Z, Liu D, Liu S, Zhang S, Pan Y. The Role of Porphyromonas gingivalis Outer Membrane Vesicles in Periodontal Disease and Related Systemic Diseases. Front Cell Infect Microbiol. 2021 Jan 28;10:585917. PMC free article
  3. Karlsson WK, Harboe ZB, Roed C, Monrad JB, Lindelof M, Larsen VA, Kondziella D. Early trigeminal nerve involvement in Listeria monocytogenes rhombencephalitis: case series and systematic review. J Neurol. 2017 Sep;264(9):1875-1884.

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