The Gut Microbiome: Implications for Brain Health and Ageing

“We are getting a much better idea, for instance, about what gut residents are beneficial and which are pathogenic. One thing has become clear: diversity is key. The greater the variety of gut microbes, the healthier you tend to be.”

Helen Thompson, journalist and editor New Scientist

“Even though Alzheimer’s is a brain disease, we need to think about the whole body when we think about how it begins.”

Donna Wilcock, PhD, Professor of Neurology, Indiana University

For decades, scientists have known about connections between the gut microbiome and the brain (the gut-brain axis). But as Dr. Eric Topol stated: “[T]here has recently been an unprecedented jump in our knowledge base that has transformed our expectations for its [gut-brain axis] preeminence.” (Topol, E., “The Gut-Brain Axis Takes Center Stage,” Ground Truths, June 25, 2025). In this week’s Germ Gems, I share some recent discoveries shaping the field.

The gut microbiome: a recap. Microbiome refers to the microbes that share our body surfaces. We all harbor four microbiomes—skin, gut, oral cavity, and lungs—and females are endowed with a fifth microbiome—vaginal. The composition of the microbiome in our bodies is different in each of us but the function is the same: to keep our body running smoothly.

Scientists have intensively studied each of these microbiomes for its role in health and disease. By far, the gut microbiome has captured the most scientific attention.

The gut contains approximately 10 to100 trillion microbial cells. Most studies of the gut microbiome have focused on its bacterial residents (from over 1,000 different bacterial species). But the gut is also home to an even greater number of viruses (the virome) that outnumber bacteria 10:1. To add to the complexity, fungi (a fungiome) and parasites are additional microbial constituents of the gut.

Many scientists have contributed to our understanding of the gut microbiome. To me, Nobel laureates Ilyich Metchnikoff and Joshua Lederberg stand out in terms of providing critical insights into its nature. (Peterson, P., “Microbiome Matters,” Germ Gems, May 21, 2025).

In the late 19^th century, Metchnikoff recognized that an imbalance of harmful versus beneficial bacteria in the human gut could result in a condition he called dysbiosis. He promoted the idea that certain kinds of bacteria found in yogurt could restore the gut to a state of eubiosis. And, at the turn of this century, Lederberg coined the term microbiome to describe “an ecological system of commensal symbiotic, and perhaps pathogenic microorganisms that reside in the human body.” (Reichel, J., “Microbiome—It Takes a Village,” https://www.lindau-nobel.org, October 16, 2019).

Part of the “hidden microbiome” revealed and another surprise finding. Researchers who study the gut microbiome deserve incredible respect for their work and for their ability to keep all of the trillions of constituents straight. And, they continue to find new bacteria in the gut.

Recently, a team of scientists at Cambridge University looked at gut microbiome samples from over 11,000 people across 39 countries and found a previously unstudied group of bacteria—called CAG-170—was consistently higher in healthy people than in those with diseases including inflammatory bowel disease, obesity and multiple sclerosis. (de Silva, A.C., et al., “Meta-analysis of the uncultured gut microbiome across 1115 global metagenomes revels a candidate signature of health,” Cell Host & Microbe, March 11, 2026).(CAG-170 is a group of gut bacteria known only from their genetic fingerprints; scientists have never been able to grow most of them in the lab.) These findings mean that CAG-170 could be used in the future as an indicator of our gut microbiome health.

As Dr. Alexandre Almeida, the researcher who led the work, said: “Our work has revealed that CAG-170 bacteria—part of the ‘hidden microbiome’—appear to be key players in human health likely by helping us to digest the main components of our food and keeping the whole microbiome running smoothly.” (Harley, S., “Overlooked group of gut bacteria appears key to good health, global study finds,” Medical Xpress, February 9, 2026).

Other researchers in the UK looked at how the gut microbiome varies among babies in different parts of the world. They found that B. longum longum and B. longum infantis—both of which help to develop the immune system and prevent gut and blood infections—are found in distinct regions. (Shao, Y., et al., “Genomic atlas of bifidobacterium infantis and B. longum informs infant probiotic design,” Cell, March 19, 2026).

The researchers found that approximately “70 percent of infants from African and South Asian countries had B. longum infantis in their guts by 2 months old, compared with fewer than 2 per cent of babies from the UK, US and Sweden.” ( Wong, C., “How baby microbiomes in the West differ from those everywhere else,” New Scientist, February 18, 2026). As Dr. Shao said, “Infantis is basically missing in Western settings.” (The basis for and the implications of this finding are under investigation.)

Dementia: what does the gut microbiome have to do with it? Dementia is a general term for a decline in mental ability, such as memory loss, language difficulties, or poor reasoning. Approximately 57 million people worldwide are currently living with dementia, a number projected to rise to nearly 139 million people by 2050. Alzheimer’s disease accounts for 60-70% of these cases.

Alzheimer’s has been long been viewed as something that starts inside the brain. A recent genomic analysis, however, suggests it may be initially triggered by inflammation in distinct organs like the skin, lungs, or gut. (Cunha, C., et al., “Genomic partitioning of Alzheimer’s disease in human reveals non-CNS etiology,” medRxiv, February 11, 2026). This could occur decades before a person’s memory starts to decline and may “mean we have to totally rethink how we approach preventing and treating the condition.” (Klein, A., “Alzheimer’s may start with inflammation in the skin, lungs or gut,” New Scientist, March 5, 2026).

This radical reframing of the disease may explain why Alzheimer’s drugs have been disappointing to date; they act too late in the disease process. As Cesar Cunha at the Novo Nordisk Foundation Center for Basic Metabolic Research in Denmark said: “If Alzheimer’s disease really is caused by peripheral inflammation, we need to take different approaches to treating it.”

According to Alice Klein, PhD, “One promising lead is that vaccination in midlife seems to be protective against Alzheimer’s disease.” She cited a recent study that found that adults who received both does of the shingles vaccine were about 50% less likely to develop Alzheimer’s disease by age 65 and onwards. She also cited a study that found that “people aged 50 or older who received the Bacillus Calmette-Guerin vaccine as a bladder cancer treatment had a 20 percent lower risk of getting Alzheimer’s.”

Diversity is key. There isn’t a distinct gut microbiome associated with ageing. But those who make it successfully to one hundred years (centenarians) possess a unique, highly diverse gut microbiome.

As we age, our microbiome changes. The number of microbes making short-chain fatty acids reduces while the proinflammatory ones increase. (Thomson, H., “Why caring for your microbiome is crucial if you want to live to 100,” New Scientist, September 16, 2025).

As Jessica Schneider, chief scientific officer at Corundum Systems Biology said, “This imbalance is thought to contribute to chronic, low-grade inflammation, a state known as inflammaging, which is associated with higher risk of conditions such as cardiovascular disease, dementia, and stroke.” The gut microbiomes of people who reach extreme old age seem to be better able to resist this decline. Their gut microbiota signatures show similarities to those of young people. Researchers speculate that this factor contributes to longevity.

The gut microbiome in human health. We have come a long way from the days of Metchnikoff in understanding the role that the microbiome plays in human health. We now know that our microbiome influences everything from digestion to metabolism to brain function.

In this week’s Germ Gems post, I’ve only scratched the surface of research implicating the gut microbiome in brain health and ageing. Some of the hottest topics, like new anti-ageing vaccines and the “off-target” benefits of commonly used vaccines, which may or may not involve the gut microbiome, are left for future discussion. Also, I haven’t even mentioned what is likely to be the most important topic of all, that is, how one’s diet may influence the gut microbiome-brain axis.

There is so much more to learn. Agencies of the Federal Government, such as the National Institutes of Health, US Food and Drug Agency, and Centers for Disease Control and Prevention, should be receiving more support to foster this area of education/research. We all stand to benefit.