The Oral-Gut-Brain AXIS: The Influence of Microbes in Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is one of the most frequently diagnosed neurodegenerative disorders worldwide and poses a major challenge for both affected individuals and their caregivers. AD is a progressive neurological disorder associated with high rates of brain atrophy. Despite its durable influence on human health, understanding AD has been complicated by its enigmatic and multifactorial nature. Neurofibrillary tangles and the deposition of amyloid-beta (Aβ) protein are typical pathological features and fundamental causes of cognitive impairment in AD patients. Dysbiosis of oral and gut microbiota has been reported to induce and accelerate the formation of Aβ plaques and neurofibrillary tangles. For instance, some oral microbes can spread to the brain through cranial nerves or cellular infections, which has been suggested to increase the risk of developing AD. Importantly, the interaction between intestinal microbiota and brain cells has been recognized as influencing the development of AD as well as other neurodegenerative diseases. In particular, the metabolites produced by certain intestinal microorganisms can affect the activity of microglia and further mediate neuroinflammation, which is a leading cause of neuronal necrosis and AD pathogenesis. Which pathogens and associated pathways are involved in the development and progression of AD remains to be elucidated; however, it is well-known that gut microbiota and their metabolites can affect the brain by both direct and indirect means. Understanding the specific mechanisms involved in the interaction between these pathogens and the nervous system is vital for the early intervention in AD. In this review, we aim to comprehensively discuss the possible mechanistic pathways underlying the oral-brain, the gut-brain and the oral-gut-brain associations.

From Mouth to Brain: Distinct Supragingival Plaque Microbiota Composition in Cerebral Palsy Children With Caries

“…Although the same severity of caries based on DMFT/dmft was shown in NCPCS and CPCS, the enrichment of P. endodontalis and P. micra indicates deeper caries progression in CP children. The SPM of CP children and their toxic metabolite [e.g., short-chain fatty acid (SCFA)] may invade the pulp through dentinal tubules, causing irreversible pulpitis and even invading the bloodstream via the pulp capillaries ( Figure 7 ) ( Narengaowa et al., 2021 ).…”

Deep nasal sinus cavity microbiota dysbiosis in Parkinson’s disease

“…This location is more likely to impact PD pathology, consistent with Braak’s hypotheses and PD subject autopsy data 7 . Prior studies have demonstrated that microbial communities are distinct in different parts of the body including different skin sites 20 , multiple locations along the GI tract 21 , and different locations within the oral cavity 22 . Similarly, we hypothesized that the deep nasal sinus cavity microbiome is unique, and that data from the oro-nasal cavity may not sure as a viable proxy for the deep nasal sinus cavity microbiome.…”

Association Between Oral Microbiota and Human Brain Glioma Grade: A Case-Control Study

“…Previous studies have shown that oral microbiome significantly affected the composition of gut microbiome ( Hou et al, 2021 ; Pandya et al, 2021 ; Park et al, 2021 ). The oral microbiome and gut microbiome can spread to the brain through cranial nerves or cellular infections or produced certain metabolites to affect the brain by both direct and indirect means ( Dominy et al, 2019 ; Jing et al, 2021 ; Narengaowa et al, 2021 ; Vyhnalova et al, 2021 ; Wang et al, 2021 ). Our results showed significant differences in oral microflora between HGG patients and HCs; oral Patescibacteria was significantly decreasing during the progression of glioma malignancy.…”