In the previous article, we discussed limitations of current drug treatment approaches for Alzheimer’s disease (AD) and the growing understanding about the importance of lifestyle and health behaviours. This is where the gut microbiome comes in. How could the microbiome be involved? The bidirectional communication that takes place between the gut microbiota and the central nervous system has been coined the now popular term “gut-brain axis” that we write about here often. Our knowledge of this phenomenon has increased rapidly over recent years with the gut now associated with mental health and neurological conditions including depression, Parkinson’s disease, Huntington’s disease, and autism spectrum disorders. A small but convincing body of research also suggests a critical role of the microbiome in AD. Animal studies have shown that the microbiome and its metabolites play a causal role in AD by modulating blood-brain barrier permeability and amyloid levels. Additionally, preliminary data also show microbiome differences in people with early AD. Animal studies in the mouse and fruit fly have shown links between the microbiome and aging. One 2017 study found aged mice to exhibit a greater number of anxiety-like behaviours coupled with reduced overall locomotor activity, behaviours also noted in human AD. Interestingly, the relative abundance of Porphyromonadaceae – a family of bacteria associated with cognitive decline – was found to be directly correlated with these anxiety-like behaviours in the aged mice, and microbiota diversity differed significantly between the young and aged mice. Additionally, Wu et al.,used a fruit fly AD model to investigate the possible link between intestinal infection and neurodegeneration. Adult flies with Alzheimer’s pathology in their brains were obtained and their gut microbiome was changed by giving them an infection with a non-pathogenic enterobacteria, known to colonize the gastrointestinal tract. This infection was found to exacerbate the progression of AD disease. Results from human studies produce similar results. A case-control observational study found that gut microbiomes of those with AD were less diverse than those of healthy controls. More specifically, AD microbiomes had less Firmicutes and Actinobacteria, and more Bacteroidetes than microbiomes of those without AD. Where to from here? Research in humans is very much in its infancy and has a way to go until we can translate these to clinical practice. The main limitation with the few human studies conducted thus far is that they are limited to people who already have an AD diagnosis. This is problematic because the brain pathology of AD begins many years before symptoms begin and, because medications prescribed to patients may also affect the gut microbiome. By studying healthy participants and tracking subtle brain changes that are indicative of AD risk, a new project we are conducting will address these limitations and enable new insights about prevention of AD. The Healthy Brain Project is aiming to recruit 10,000 healthy Australians and follow their brain health over at least 5 years. A smaller number of participants residing in Victoria will be invited to participate in a biomarker sub-study which includes sampling of the gut and oral microbiomes. Other measures in this sub-study include a blood test, MRI scan, cerebrospinal fluid sample and a neuropsychological assessment. Do you live in Australia and want to participate in the Healthy Brain Project? We are seeking adults aged 40-70 years old. Visit the Healthy Brain Project websitefor more information and to sign up as a participant! Madeline West is an Associate Nutritionist and research assistant currently working at the Food & Mood Centre on the Healthy Brain Project (Microbiome substudy). Dr Amy Loughman is a post-doctoral research fellow at the Food & Mood Centre specialising in gut microbiome research and leading the Healthy Brain Project (Microbiome substudy). She is an avid science writer and author of the blog MindBodyMicrobiome.