alzheimer’s and the gut

What is Alzheimer’s?

In the western world, Alzheimer’s disease (“AD”) is the most frequent cause of dementia [1] and affects more than 520,000 people in the UK [5]. There is currently no cure for those suffering from AD. AD results in progressive cognitive decline due to the formation of beta-amyloid plaques at the nerve fibres in the brain. Causing nerve cells to die and the loss of brain tissue [2].

 

What has it got to do with the gut?

Our gut microbiota plays a fundamental role in how well the immune system works. It has recently gained a lot of traction from researchers looking at the association between the microbes in our guts and the development of AD. We know that imbalances in the gut microbiota may contribute to the disruption of the gut-brain axis and central nervous system [2]. Resulting in an increased risk of neurodegenerative disorders.

Research in mice showed that mice suffering from Alzheimer’s had a different composition of their gut microbiota (Allobaculum and Akkermansia were decreased) to those mice who didn’t. In this particular study, the researchers transferred bacteria from the AD mice to those without. And they developed more of the beta-amyloid plaques in the brain [1]. Interestingly, reduced levels of Akkermansia are associated with an increased risk of obesity and type two diabetes [4], which are risk factors for dementia [3]. Further research in humans has suggested that the composition of the gut microbiota changes as AD progresses. Which may give further information as to the species of bacteria involved in this neurodegenerative condition [6].

As we get older, the composition of the gut microbiota may become dysbiotic due to the altered diversity and stability of the microbes living in the gut. Pathogenic microbes can promote dysbiosis and produce lipopolysaccharides. This stimulate immune activity and the increasing permeability of the gut barrier resulting in systemic inflammation around the body. A persistent state of systemic inflammation can contribute to neurodegeneration. Increased inflammatory markers have been observed in those with AD [2].

 

What’s next?

The research on the gut microbiota and neurodegenerative disorders is still very much in its infancy and ethics plays an important role as to why there are limited studies on humans. However, from the research we do have, it is clear that there is an association between gut microbiota and neurodegenerative disorders, such as AD but we still don’t really understand how the microbes and their by-products interreact and increase or decrease the risk of AD. With more research, the future may see interventions at a gut microbiota level to reduce risk or even treat AD but we are a long way off yet.

For more information on AD, visit www.alzheimers.org.uk.

 

References

1. Harach, T. et al. Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota.  Rep.7, 41802; doi: 10.1038/srep41802 (2017).
2. Kowalski K, Mulak A. Brain-Gut-Microbiota Axis in Alzheimer’s Disease. J Neurogastroenterol Motil. 2019;25(1):48–60. doi:10.5056/jnm18087
3. Walker JM, Harrison FE. Shared neuropathological characteristics of obesity, type 2 diabetes and Alzheimer’s disease: impacts on cognitive decline. Nutrients. 2015;7:7332–7357. doi: 10.3390/nu7095341.
4. Everard A, Belzer C, Geurts L, et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Nati Acad Sci USA. 2013;110:9066–9071. doi: 10.1073/pnas.1219451110.
5. alzheimers.org.uk
6. Saji, N., Niida, S., MSaji, N., Niida, S., Murotani, K. et al. Analysis of the relationship between the gut microbiome and dementia: a cross-sectional study conducted in Japan. Sci Rep 9, 1008 (2019) doi:10.1038/s41598-018-38218-7