The Gut–Brain connection: What the gut microbiome could teach us about Alzheimer’s Disease

The information presented in this article is based on a recent scientific review by Dong-oh Seo and David M. Holtzman, “Current understanding of the Alzheimer’s disease–associated microbiome and therapeutic strategies,” published in Experimental & Molecular Medicine (2024). 

A second brain in your gut 
Our intestines are home to trillions of bacteria, viruses, and fungi. Together they form an ecosystem so large and complex that scientists sometimes call it our “second brain”. These tiny organisms help us digest food and make vitamins, but they also communicate with the brain through nerves, hormones, and the immune system — a communication network known as the gut–brain axis. 

When this ecosystem is in balance, it supports healthy metabolism and a strong immune system. But when it becomes disturbed, a state called dysbiosis, the gut can start sending “stress signals” throughout the body, including the brain. These signals can trigger inflammation and metabolic changes that may contribute to neurological diseases, including Alzheimer’s. Think of it like a neighborhood where the balance between helpful and disruptive residents has shifted, and the noise and tension affect the entire city. In fact, the very word dysbiosis comes from the Greek roots δυσ- (“bad” or “difficult”) and βίος (“life”), reflecting this imbalance and highlighting how a disrupted community can create stress and disorder. 

What science shows 
In people with Alzheimer’s and even in those with mild cognitive impairment, the composition of gut bacteria often looks different from that of healthy individuals. Some studies have found fewer bacteria that help reduce inflammation and more that may promote it. But the results are not always consistent across studies, possibly because of differences in diet, lifestyle, or genetics. This suggests that it may not be single “bad” or “good” types of bacteria that matter most, but the overall balance and functional diversity of the microbial ecosystem. 

How might this happen? 
Scientists describe two main ways the gut might affect the brain: 

1. Direct effects of microbes or their products on the brain:  
   Some bacteria or viruses can travel through the body and may reach the brain. For example, herpes viruses or the gum-disease bacterium Porphyromonas gingivalis have been found in some brains of people with Alzheimer’s. Some researchers even think that amyloid proteins, a key protein in Alzheimer’s disease, might form as the brain’s ancient defense mechanism fights against such infections, acting like a sticky net that traps invaders. 
2. Indirect effects through the immune and metabolic systems:  
   This is likely the bigger story. The gut ecosystem constantly “talks” to our immune system, shaping how immune cells develop and how strongly they respond. When the ecosystem is out of balance, immune cells can become overactive, sending inflammatory signals through the body that may activate the brain’s own immune cells called microglia.  
   
   Imagine the gut as an early warning center: If it sends too many alarms, the brain’s immune system can stay on high alert, which over time may harm brain cells instead of protecting them. 

Gut bacteria also produce tiny molecules called short-chain fatty acids (SCFAs) when they break down dietary fiber. Under healthy conditions, SCFAs are beneficial: they nourish gut cells and help calm inflammation. But in Alzheimer’s, their effects can be more complicated. Depending on the type and amount, SCFAs might reduce or worsen inflammation. This is one reason why even “healthy” habits like very high-fiber diets might not have the same benefits for everyone. 

Genes, sex, and individuality  
Genetics can influence how the gut microbiome interacts with the brain. For example, the APOE gene, the strongest known genetic risk factor for late-onset Alzheimer’s, also appears to influence gut bacterial composition. People with the APOE4 gene tend to have fewer bacteria that produce helpful SCFAs, while those with the APOE2 gene tend to have more. Sex differences have also been observed: research suggests that changes to gut bacteria may affect males and females differently, possibly due to hormones and immune system differences. These findings show that there is no single “one-size-fits-all” microbiome for Alzheimer’s disease. 

Can we change the gut to help the brain? 
If the gut affects the brain, could adjusting its ecosystem help prevent or slow Alzheimer’s? Researchers are exploring several approaches: 

• Fecal microbiota transplantation (FMT): moving gut microbes from a healthy donor into a patient’s gut. Early animal studies and a few case reports in humans suggest that FMT can reduce plaques and improve cognition, but much more research is needed. 
• Probiotics and prebiotics: introducing beneficial bacteria, or nutrients that help them grow. Some small studies using bacteria such as Bifidobacterium or Akkermansia muciniphila have shown improvements in inflammation and cognitive function. 
• Dietary strategies: eating more fiber, following a Mediterranean-style diet, and reducing processed foods may support a healthier microbiome, though the best balance for brain health is still unclear. 
• Emerging strategies: scientists are also exploring “postbiotics,” which are helpful by-products produced by bacteria, or viruses that target harmful bacteria. 

It is important to highlight that it is too early to make clinical recommendations. Current evidence suggests it is not a single “bad” or “good” type of bacteria that matters most, but the overall balance and diversity of the gut ecosystem. First, we need standardized protocols, long-term trials, and a clearer understanding of which microbial functions (rather than specific species) most affect the brain. 

What we can take from this today 
The discovery that gut microbes may shape brain aging adds a new perspective to Alzheimer’s research. It connects lifestyle, genetics, and biology in a more integrated way. This does not mean Alzheimer’s starts in the gut, but it does show that brain health depends on the whole body. 

For now, no microbiome-based therapy or specific diet can be recommended for Alzheimer’s. As Drs. Seo and Holtzman conclude in their recent review, the microbiome represents “a promising new avenue to slow Alzheimer’s progression,” but turning that promise into practice will require much more research, and time. 

That said, this area of research reminds us that the brain is not isolated from the rest of the body. How we eat, move, and care for our overall health can affect many biological systems, including the gut. Everyone is different, so understanding what supports your wellbeing should always be discussed with healthcare professionals who know you.