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Feed Your Microbes: How Diet Influences the Gut Microbiome and Health

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On June 27, people across the globe recognize World Microbiome Day. Each year, this event celebrates achievements in microbiome research and recognizes the importance of the microbiome in the health of humans, animals, plants and the planet.

The theme for World Microbiome Day 2024 – “Feed your microbes – How diet shapes your gut microbiome” – reflects the current interest in understanding how diet can impact the gut microbiome and consequently influence human health.

Various bacteria, viruses, fungi and other microbes live inside our gut, collectively known as the gut microbiome. Though relatively stable throughout an organism’s life, diet can play an important role in maintaining this microbiome.

Changes in gut microbiome composition have been linked to fluctuations in our immune and metabolic health, and even our behavior. In this article, we highlight some of the latest scientific findings detailing how diet can affect the gut microbiome and the impact the gut microbiome can have on our behavior.

The ever-evolving gut microbiome

The eating habits of industrialized societies differ greatly from those of our hunter-gatherer ancestors. This change has altered our gut microbiome, according to a study published in Science.

In the study, researchers identified previously unknown species of Ruminococcus bacteria. This bacterium produces cellulosomes, a key component of fiber metabolism that forms part of a healthy gut microbiome.

The study showed that the cellulosome-producing bacteria of modern humans appear to have been acquired from livestock domesticated earlier on in human evolution. These strains of Ruminococcus were shown to be highly prevalent and abundant in ancient human populations, among hunter-gatherer communities and rural societies. However, the study revealed that these strains are sparse or missing in human samples from modern industrialized societies.

The authors concluded that a shift away from a fiber-rich diet could be an explanation for the loss of these important cellulose-degrading microbes in the microbiome. They suggest that there may be potential for reintroducing or enriching these species with diet choices and specialized probiotics.

Promoting healthy bacteria in the gut

There is growing evidence supporting the therapeutic utility of altering microbial composition through diet to improve overall health. Experiments have shown that dietary alterations can induce large, temporary microbial shifts within just 24 hours.

The high content of (poly)phenols present in cranberries has been associated with multiple health benefits. However, due to the high variability associated with gut microbiota interactions with these molecules, clinical studies attempting to demonstrate positive effects have had mixed results. A study, published in npj Biofilms & Microbiomes, evaluated the effects of cranberry extracts on the gut microbiota to better understand this variability.

A total of 39 healthy participants took cranberry extract supplements twice daily for 4 days, the equivalent of ingesting 60 grams of fresh cranberries per day. Plasma samples were collected from the 39 participants and 28 subjects provided 2 fecal samples, which were provided on the day before and the day after the 4-day study period.

After comparing the samples, the researchers observed that the number of Bifidobacterium substantially increased while the number of Bacteroides significantly decreased over the study period.

As Bifidobacteria have previously been linked with lower levels of inflammation, the researchers suggest that cranberry extracts could help lower the risks of diabetes and cardiometabolic diseases. Not all the effects of the cranberry extract may be beneficial, however, as Bacteroides have been associated with lower cases of obesity.

The research team is now interested in exploring the long-term effects of the extracts and identifying which microbiota signatures respond best to such extracts.  

Meal timing and feeding frequency to improve gut health

It isn’t just what you eat, but how you eat that may impact your gut microbiome.

Intermittent fasting (cycling between periods of fasting and eating) and protein pacing (controlled protein intake at specific meals) have recently gained popularity for their potential health benefits.

To better understand the effects of these dietary changes on the gut microbiome, Arizona State University researchers compared the effects of a heart-healthy, calorie-restricted diet (based on U.S. Department of Agriculture (USDA) dietary recommendations) and a calorie-restricted regimen incorporating intermittent fasting and protein pacing.

The results, published in the journal Nature Communications, showed that participants following the intermittent fasting and protein-pacing regimen experienced increased beneficial gut bacteria and higher levels of circulating cytokines and amino acid metabolites that favored fat oxidation.

“While limited in duration and sample size, this comprehensive investigation — which included the analysis of the gut microbiome, cytokines, fecal short-chain fatty acids and blood metabolites — underscores the intricate interplay between diet, host metabolism and microbial communities,” said Alex Mohr, lead author of the study.

“These findings highlight the importance of personalized approaches in tailoring dietary interventions for optimal weight management and metabolic health outcomes,” the researchers said.

How does the gut microbiome influence behavior?

Increasing evidence of the microbiome's influence on human health and disease has led to a rise in clinical trials investigating the utility of fecal microbiota transplantation (FMT) in treating the symptoms of a range of conditions, including Parkinson's disease.

In addition to its influence on health, research has also suggested that the microbiota living in and on animals may play an important role in social architecture and behavior.

What is fecal microbiota transplantation (FMT)?

FMT is used to administer fecal matter from a donor into the intestinal tract of a recipient to directly change the recipient’s gut microbial composition and confer a health benefit. The microbiota is transferred from a donor into the recipient’s intestines either using a liquid or capsule preparation of FMT. 

Neurological disorders such as autism spectrum disorder (ASD) are often associated with gastrointestinal (GI) symptoms. However, it is unclear whether GI distress itself can modify aspects of behavior.

Now, scientists at the University of Utah Health have shown that frequent GI distress can reduce social behaviors in mice. They also showed its possible to alleviate GI symptoms and the behavioral changes they provoke by introducing specific species of bacteria into the animals’ guts. The findings were published in the journal Nature Communications.

“Collectively, our study suggests that individuals with neuro-developmental diseases might harbor a microbiota that promotes intestinal inflammation, and that this inflammation may also exacerbate specific aspects of their behavioral outcomes,” the researchers said.

The researchers induced mice with colitis, an inflammatory condition that causes pain and diarrhea. After several rounds of colitis, the animals’ symptoms were allowed to subside before behavioral testing. Mice that had experienced colitis showed no signs of anxiety or depression. However, they spent less time interacting with unfamiliar mice than mice that had not experienced the condition. The researchers observed that this reluctance to socialize was reminiscent of the social impairments associated with autism.

To further explore the differences in the microbes of individuals with ASD and those of neurotypical individuals, the scientists collected stool samples from each group and delivered the microbe-filled samples to the GI tracts of mice.

Certain species of Blautia bacteria were found to be better represented in neurotypical individuals. In addition, among mice colonized with microbes from autistic people, Bacteroides uniformis was more abundant in those whose colitis was less severe.

Investigating the effects of oral treatment of the bacteria, the researchers delivered both groups of bacteria to mice before inducing colitis. It was observed that both Blautia and Bacteroides uniformis reduced intestinal problems. Blautia had a corresponding effect on social behavior, with animals that received this bacterium more likely than other mice to engage with unfamiliar mice following colitis.

“This is an example where we are missing microbes, and missing these beneficial microbes is driving disease,” said Dr. June Round, a microbiologist at University of Utah Health who led the research.

Future work plans to explore the use of these bacteria in other animal models of disease to evaluate their potential use in targeted therapies.

Towards targeted microbiota replacement therapy

Scientists continue to untangle the relationship between diet and the microbiome and what influence this may have on health and behavior. Knowledge obtained through this research could be used to inform the choice of specific microbial entities that would be effective for use in targeted FMT.

These therapies could one day be used as a treatment option for many neuro-developmental and cardiometabolic diseases and as an intervention to improve social decision-making in health and disease.