There is a strong link between Alzheimer’s disease and chronic inflammation1. In fact, patients with Alzheimer’s often suffer from concomitant inflammatory diseases such as depression and rheumatoid arthritis, and the underlying inflammation seems to accelerate brain aging.
The explosion of research on the microbiota has highlighted its role in chronic low-grade inflammation. An immune system that is immature or disturbed by stress, infections, or diet could be a common source of all these pathologies. in particular, disturbances during development (in utero and then in childhood) leave a lasting imprint that promotes chronic inflammation and disease. The microbiota itself can bear this imprint, in particular through changes in its composition. Numerous studies have reported alterations in the composition of the gut microbiota in patients with Alzheimer’s disease. Certain gut bacteria are even being studied as potential treatments for dementia2. The gut microbiota is by far the most abundant, but our body also hosts an entire microbial ecosystem in the mouth and lungs and on the skin and more generally on all mucous membranes. The gut microbiota is by far the most abundant, but our body also hosts an entire microbial ecosystem in the mouth and lungs and on the skin and more generally on all mucous membranes.3,4 (as well as in other diseases with an inflammatory component such as rheumatoid arthritis5). Indeed, a certain proportion of patients with Alzheimer’s also suffer from periodontitis, and vice versa. Moreover, a correlation between the severity of gum disease and the severity of dementia has been observed4,6.
Among the specific pathogenic bacteria found in periodontitis, certain species such asP. gingivalis could play a particular role in this association. P. gingivalis seems to have the ability to infiltrate the brain, as its DNA has been detected in both Alzheimer’s patients and animal models of experimentally induced gingivitis.7. However, even in the absence of P. gingivalis, animal studies have shown an increase in neurodegeneration (the phenomenon responsible for dementia) when the gums are inflamed, suggesting that mechanisms related to the inflammation itself, such as the migration of immune cells activated in the gums to the brain, may contribute to the association between periodontitis and Alzheimer’s disease.8,9.
It remains to be determined to what extent the oral microbiota can affect these diseases independently of the intestinal microbiota. Indeed, these different microbiota interact constantly. For example, the presence of certain oral bacteria has been observed in the gut of patients with chronic digestive diseases.10–12.
In conclusion, there is considerable evidence implicating the gut microbiota, as well as the oral microbiota, in Alzheimer’s disease, though further studies are required to demonstrate a causal role.
References
1. Heppner, F. L., Ransohoff, R. M. & Becher, B. Immune attack: the role of inflammation in Alzheimer disease. Nat. Rev. Neurosci. 16, 358–372 (2015).
2. Kesika, P., Suganthy, N., Sivamaruthi, B. S. & Chaiyasut, C. Role of gut-brain axis, gut microbial composition, and probiotic intervention in Alzheimer’s disease. Life Sci. 264, 118627 (2021).
3. Dioguardi, M. et al. The Role of Periodontitis and Periodontal Bacteria in the Onset and Progression of Alzheimer’s Disease: A Systematic Review. J. Clin. Med. 9, (2020).
4. Beydoun, M. A. et al. Clinical and Bacterial Markers of Periodontitis and Their Association with Incident All-Cause and Alzheimer’s Disease Dementia in a Large National Survey. J. Alzheimers Dis. JAD 75, 157–172 (2020).
5. Hajishengallis, G. & Chavakis, T. Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities. Nat. Rev. Immunol. 1–15 (2021) doi:10.1038/s41577-020-00488-6.
6. Noble, J. M. et al. Serum IgG Antibody Levels to Periodontal Microbiota Are Associated with Incident Alzheimer Disease. PLoS ONE 9, (2014).
7. Dominy, S. S. et al. Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. Sci. Adv. 5, eaau3333 (2019).
8. Kantarci, A. et al. Combined administration of resolvin E1 and lipoxin A4 resolves inflammation in a murine model of Alzheimer’s disease. Exp. Neurol. 300, 111–120 (2018).
9. Kantarci, A. et al. Microglial response to experimental periodontitis in a murine model of Alzheimer’s disease. Sci. Rep. 10, 18561 (2020).
10.Gevers, D. et al. The treatment-naive microbiome in new-onset Crohn’s disease. Cell Host Microbe 15, 382–392 (2014).
11.Schirmer, M. et al. Compositional and Temporal Changes in the Gut Microbiome of Pediatric Ulcerative Colitis Patients Are Linked to Disease Course. Cell Host Microbe 24, 600-610.e4 (2018).
12.Atarashi, K. et al. Ectopic colonization of oral bacteria in the intestine drives TH1 cell induction and inflammation. Science 358, 359–365 (2017).
Author
Marion Rincel