The gastrointestinal tract is one of the most densely populated microbial habitats on earth, containing more cells than those that make up the human body and 150 times the number of genes than exist within the human genome. An unhealthy gut environment is characterized by a reduction in the diversity of bacteria and increased gut barrier permeability, leading to the release of toxic metabolites into the blood stream that negatively impact the brain. Lifestyle factors such as healthy diet and exercise improve the diversity and function of the gut microbiome, which may represent a therapeutic target for lowering dementia risk.
How are exercise and diet thought to impact the brain via the gut microbiome?
Diets high in saturated fats and simple sugars are associated with reduced microbiome diversity and increased intestinal permeability and inflammation. By contrast, diets high in fruits and vegetables, legumes, nuts, and fish are associated with improved gut microbiome diversity, intestinal health, and a reduction in inflammation. Potential mechanisms include metabolites such as short chain fatty acids (SCFAs) and omega-3 polyunsaturated fatty acids (PUFAs), which help to maintain the integrity of the gut barrier and exhibit neuroprotective properties.
Aerobic exercise has been shown to improve microbial diversity and intestinal barrier integrity, leading to a reduction in systemic and neural inflammation. Potential mechanisms include increases in SCFAS and brain-derived neurotrophic factor (BDNF). The effects of diet and exercise on brain health may be mediated by changes to the gut microbiome, however, very few studies have examined these relationships in a clinical setting.
What evidence is out there?
We conducted a literature review of diet and exercise interventions, which included both microbiome and cognitive outcomes. We found 22 completed trials, almost all which were rodent studies, mostly utilizing detrimental-type diets. Of the studies that investigated beneficial diets, most used single nutrient interventions such as fiber, PUFAs, and polyphenolic compounds. One diet intervention included older adults and studied the effects of a “Mediterranean” diet on gut microbiota and cognition. Very few exercise interventions were identified (n=3).
Review of the findings
Diet and exercise interventions consistently altered the gut microbiome. Detrimental diets led to impaired memory performance, which was associated with decreases in neurotrophic factors and increased local, systemic, and neural inflammation. On the contrary, beneficial diets and aerobic exercise resulted in improved memory and reductions in age- and AD-related impairments, and were associated with increased SCFAs, neurotrophic factors, and reductions in local, systemic, and neural inflammation.
Following high adherence to a “Mediterranean” diet in older adults, altered microbiota were associated with changes in overall cognition. In rodents, microbiota changes were found to precede cognitive improvements resulting from a high-fiber diet intervention and diet-associated cognitive improvements were reversed when rodents were administered antibiotics intended to disrupt gut microbiota. In a novel microbiota transplant design, mice who had their microbiome depleted with antibiotics were transplanted with fecal matter from mice fed a high fat diet or normal chow diet. The high-fat diet fecal transplant altered microbiome diversity and composition, increased permeability and inflammation, and lowered memory performance. These studies provide evidence for the mediating role of the microbiome, but are limited by heterogeneous rodent strains, mostly male rodents, narrow selection of cognitive tests, and lack of proper mediation analyses.
Areas requiring further investigation
Our review of the trials and findings indicates three key research areas requiring further investigation:
1. Human trials
The role of the microbiome in the effects of diet and exercise on cognition is emerging from pre-clinical trials, but the relevance to humans, especially in the context of dementia prevention is uncertain. There is a need for more human trials, in particular those that include at-risk older adults. Due to the frequent use of maze testing and fear conditioning paradigms to assess memory in rodents, little is known about other cognitive domains that can be differentially impaired in humans experiencing dementia.
2. Whole diets
The effects of beneficial whole diets on microbiota and cognition are also underexplored. The general consensus is that the combined attributes of a diet are more important than individual components for brain health. Thus the effects of whole diets high in fruits vegetables, legumes, nuts, and fish on gut microbiota and cognition are recommended for future studies in this area.
3. Exercise type and intensity
The number of exercise trials in this area is limited and little is known about how exercise type and intensity influence gut-brain communication. For instance, the effects of resistance exercise, or high intensity aerobic exercise such as HIIT training. As multicomponent interventions including diet and exercise in older adults are increasingly common, it is of interest whether synergistic effects on the microbiome are present. Factorial designs comparing diet, exercise, and both combined are required.
In conclusion, the intervention literature supports the notion that the gut microbiome mediates diet and exercise effects on cognition. The evidence is mainly derived from rodent studies and there are several gaps in the research that require further investigation. There are numerous studies investigating the effects of diet and exercise on cognition in older adults, but lacking investigation into the microbiome. We encourage researchers working on these studies to attempt to include simple, cost-effective measures of microbiota composition, diversity, and function, and measure potential mediating factors such as SCFAs, BDNF, and local and systemic inflammation. This effort would help to elucidate the mechanisms by which lifestyle modification affects cognition and possibly help to better tailor interventions for dementia prevention in older adults.