A number of physiological and psychological changes occur as we age, and many studies have shown that our gut microbiome also changes as we grow older. A fascinating new study is suggesting that a shift in gut bacteria in our middle-age could trigger a process that plays a role in cognitive decline in our later years. And diet may be the key to encouraging the growth of beneficial bacteria that benefit healthy brain aging.

The new study, led by scientists from University College Cork, set out to explore how microbiome changes in middle-age can influence brain immune cell function, and how dietary alterations can moderate those age-related changes. The researchers hypothesized that by disrupting those gut bacteria changes that may ultimately lead to cognitive decline they could prevent, or at least slow, age-related neuroinflammation and cognitive decline.

"The community of microbes in the gut changes with aging," says John Cryan, from APC Microbiome Ireland and lead researcher on the project. "Many studies in aging focus on very old animals and this may be too late to reverse the age-associated changes. We chose middle age in the hope that we could promote healthy aging."

Instead of directly modulating gut bacteria with probiotics, the study focused on prebiotics – non-digestible compounds in food that stimulate the growth of good bacteria. The prebiotic in this study is called inulin, a fibrous carbohydrate found in thousands of different plants including garlic, wheat, chicory and bananas. Because inulin is not broken down in the stomach through normal digestion, it becomes highly available to bacteria in the large intestine and is known to stimulate the growth of intestinal bifidobacteria.

"We wanted to see whether an inulin enriched diet that can modulate the composition of the microbes in the gut could also improve brain health and wellbeing," explains Cryan.

The study compared a cohort of young mice (8 weeks old) with a group of middle-aged mice (10 months old). For 14 weeks the animals' diets were supplemented with oligofructose-enriched inulin. The results revealed significant prebiotic-driven changes in the microbiome of both the middle-aged and young mice. Increases in Bifidobacterium across both cohorts of mice were predictably identified, but interestingly the diet seemed to drive an increase in Akkermansia bacteria in the middle-aged mice, to a level similar to that of younger mice.

Most interesting were the neurological changes in the inulin-fed middle aged mice, compared to a similarly aged control group eating a normal diet. Alongside a reduction in several age-related neuroinflammatory pathological characteristics, the middle-aged mice displayed improvements in cognitive tests and reductions in anxiety-like behavior. Curiously, the researchers note other studies using mixes of probiotics have not found similar anxiety-like behavioral improvements. This suggests prebiotics, or dietary intervention, could be more effective at altering the microbiome to improve behavior.

"Our research shows that a diet supplemented with prebiotics reversed microglia activation in the middle- aged mouse brain towards young adult levels," says Marcus Boheme, first author on the study. "Moreover, this reversing effect was observed in a key region of the brain which regulates learning and memory, the hippocampus. Microglia are the major immune cells in the brain and have shown to be a key player in neuropsychological and neurodegenerative conditions. Moreover, microglia play a crucial role in brain plasticity and cognition."

This interesting new study certainly adds weight to the hypothesis that the microbiome can causally influence many physiological and psychological changes often associated with aging. However, there still is cause for some skepticism as this study is only proven in mice. A number of compelling studies linking the microbiome to aging have only been shown in animals, and while they are incredibly promising, there is still a huge amount of work to be done before they can be translated into specific human clinical therapies.

One of the intriguing takeaways from this particular study is the implication that dietary patterns in middle age may be significantly important in laying a foundation for good brain health in later years. It seems our gut microbiome may go through its own mid-life crisis needing particular foods to help maintain gut health and positive brain aging.

The study was published in the journal Molecular Psychiatry.