Exercise reduces cognitive decline linked to gut microbiota disruption

A new study of rats with disrupted gut flora found that exercise mitigated the negative effects of this disruption on the ability of the hippocampus region of the brain to produce new neurons. This protected them from the cognitive impairments seen in rats with disrupted gut flora who led a sedentary lifestyle. The research was published in Translational psychiatry.

Human brain cells – neurons – generally stop dividing shortly after birth. After this initial period, the brain continues to change by creating new connections between neurons, but there is generally no creation of new neurons. There are some exceptions.

The hippocampus, a brain region involved in memory formation and spatial navigation, retains the ability to generate new neurons. This is called adult hippocampal neurogenesis. Studies suggest that adult hippocampal neurogenesis may play a key role in learning, memory processes, and mood regulation.

Recent studies indicate that this ability of the hippocampus to create new neurons is also influenced by gut microbiota – the trillions of microorganisms that live in the intestines. This influence is achieved via the microbiota-gut-brain axis, a bidirectional pathway that allows gut microbiota to influence processes in the brain and vice versa.

Study author Sarah Nicolas and her colleagues note that previous studies have shown that exercise improves cognitive performance in rats. Previous research has also shown that exercise can increase adult hippocampal neurogenesis in rats, that is, improve the ability of their hippocampal regions to create new neurons. These researchers wanted to see if exercise could also reduce the potential negative effects that disrupting the gut microbiota has on hippocampal neurogenesis.

They conducted a series of experiments on 9-week-old Sprague-Dawley rats, a type of rat often used in scientific research. Rats were kept on a 12-hour-12-hour light-dark cycle, i.e., with lights on for half the day and off for the other half. They had free access to food and water.

The researchers randomly divided the rats into two groups: a sedentary group and an exercise group. Each of these two groups was further divided into two subgroups: a group that would undergo antibiotic treatment (to destroy/disrupt their gut flora) and a group that would not.

The rats receiving the antibiotic treatment were given drinking water containing dissolved antibiotics. The exercise group was housed in cages with free access to a running wheel, while the sedentary group lived in standard cages without running wheels. Researchers monitored the number of revolutions of the running wheel to ensure that the exercise group was performing the intended physical activity.

Three weeks after these treatments began, the rats completed a series of behavioral tests to assess their cognitive abilities. After this, researchers euthanized the rats and analyzed their tissue to assess hippocampal neurogenesis.

The results showed that disruption of the gut flora with antibiotics did not change the rats’ body weight or their running activity. However, it did cause low-grade peripheral inflammation. The metabolism of the hippocampus was not affected by the disruption of the gut flora.

However, rats with disrupted microbiota that also led a sedentary lifestyle performed worse on behavioral tests designed to assess cognitive performance and showed more anxiety-like behavior compared to rats with intact gut microbiota. Exercise attenuated these adverse changes, as they were not present in rats with disrupted microbiota that were exercised.

Disruption of the gut microbiota reduced hippocampal neurogenesis, but this effect was attenuated in the exercised group. By examining specific biochemical compounds associated with these changes, the researchers identified the expression level of ethyl 2-(4-oxo-4,5-dihydro-1,3-thiazol-2-yl) acetate as associated with most of the observed changes.

“We observed that exercise partially reversed the behavioral and neurogenic changes induced by gut microbiota disruption and that these disturbances occurred without significant changes in the hippocampal metabolome. [a set of compounds indicative of the metabolic activity of the hippocampus), despite drastic shifts in the caecal metabolome [the metabolites present in the caecum, a pouch-like structure at the junction of the small and large intestines].”

“Taken together, these data highlight the importance of gut microbiota in AHN-dependent behaviors [behaviors that depend on adult hippocampal neurogenesis] and demonstrate the power of lifestyle factors such as voluntary exercise to mitigate these changes,” the study authors concluded.

The study sheds light on the effects of exercise on the preservation of adult hippocampal neurogenesis. However, this study was conducted on rats. Although rats and humans share many physiological similarities, they are still very different species. The effects on humans may not be identical.

The article, “Exercise minimizes a gut microbiota-mediated reduction in adult hippocampal neurogenesis and associated behaviors in rats,” was authored by Sarah Nicolas, Sebastian Dohm-Hansen, Aonghus Lavelle, Thomaz FS Bastiaanssen, Jane A. English, John F. Cryan, and Yvonne M. Nolan.

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