Link Between Gut Microbiome and Alzheimer’s Identified

A study has, for the first time, confirmed the role of the gut microbiome in Alzheimer’s disease (AD), showing that symptoms of AD can be transferred to healthy animals through fecal transplants. The research is published in Brain.

Alzheimer’s and the gut microbiome

Dementia, a general term to describe loss of cognitive ability and memory that affects everyday life, is most commonly caused by AD.

AD is strongly associated with aging and cases are expected to increase as our population steadily grows older.

Previous studies have linked AD to the gut microbiome – the population of microorganisms residing in our gut that can heavily influence our health. These show that both animal models and AD patients harbor alterations in the composition of the gut microbiome.

However, it was poorly understood whether these changes were associated with AD, or whether they could have a causal role in the symptoms of the disease.

A research team led by investigators from King’s College London went looking for answers, using fecal transplants to see if AD patients’ microbiomes could induce AD-like memory impairments in rats.

AD symptoms can be transferred

Rat models, whose microbiomes had been depleted with antibiotics, underwent fecal transplants from either AD patients or age-matched, cognitively healthy control participants. A total of 16 animals per group underwent transplantation.

Microbiome transplants from Alzheimer’s patients led to impaired behaviors that rely on a process called adult hippocampal neurogenesis, which is essential for some aspects of memory and mood. Additionally, the degree of the impairments in the rats were linked to the severity of the patient’s AD.

The study also showed that AD patients had higher levels of bacteria that promote inflammation, which was directly associated with their cognitive status.

Overall, the study’s findings confirm for the first time that the microbiome has a causal role, suggesting that AD symptoms can be transferred to young animals through gut microbiome transplants from affected patients.

“The memory tests we investigated rely on the growth of new nerve cells in the hippocampus region of the brain,” said Professor Yvonne Nolan, one of the study’s senior authors and professor of anatomy and neuroscience at University College Cork. “We saw that animals with gut bacteria from people with Alzheimer’s produced fewer new nerve cells and had impaired memory.”

“Alzheimer’s is an insidious condition that there is yet no effective treatment for,” said Professor Sandrine Thuret, one of the study’s senior authors and professor of neuroscience and King’s College London. “This study represents an important step forward in our understanding of the disease, confirming that the make-up of our gut microbiota has a causal role in the development of the disease. This collaborative research has laid the groundwork for future research into this area, and my hope is that it will lead to potential advances in therapeutic interventions.”

The authors suggest that further research should focus on possible sex-associated differences in the microbiome associated with AD, as well as comprehensive future studies assessing the impact of other factors that shape the microbiome such as lifestyle factors and medication history.

Reference: Grabrucker S, Marizzoni M, Silajdžić E, et al. Microbiota from Alzheimer’s patients induce deficits in cognition and hippocampal neurogenesis. Brain. 2023:awad303. doi: 10.1093/brain/awad303

This article is a rework of a press release issued by King's College London. Material has been edited for length and content.