Researchers harness compounds in food to improve gut microbiome

Common foods may be able to control harmful microbes in the gut while balancing microbial diversity by fostering the growth of beneficial bacteria, according to new research by San Diego State University in California and published in the journal Gut Microbes.

Foods we eat commonly affect our gut microbiota. Research shows they do so by triggering the production of bacteriophage, viruses that infect and replicate inside bacteria. Compounds in these foods have an antimicrobial effect which causes the phage to replicate, researchers said.

For the study, the researchers began by identifying which foods were antimicrobial, then analyzed them before narrowing it down to a shortlist. When examining growth curves of bacteria, they observed that while bacteria multiply over time, eventually their numbers plateau. However, if phages are activated, then bacterial growth stops altogether, and their numbers drop dramatically until they're depleted.

Foods they tested that had antimicrobial effects include honey, licorice, stevia, aspartame, hot sauce, herbs such as oregano, spices such as cinnamon and clove, rhubarbs, uva ursi or bear berry, and neem extract. They also tested toothpaste, since it's known to contain antimicrobial compounds. Of these, honey, stevia, aspartame, neem, and uva ursi had the most impact in triggering phage production.

When phage replicate, they kill the host cell and exit into the environment, which can lead to a cascade effect where they infect bacterial cells around them. Each bacterial cell that bursts, when the phage grows inside them, can have hundreds of new phages that emerge. When they release in the microbiome, if there are more bacteria present, they will continue to infect the bacteria.

Once the researchers chose foods with known and perceived antimicrobial effects, they then selected bacteria representative of the two major gut phyla, Bacteroidetes and Firmicutes, including strains of pathogenic as well as beneficial bacteria. They narrowed the food compounds down to 28 from 117 candidates on which they conducted the prophage induction assay. Bacterial growth was observed with and without food compounds, for comparison. The samples were processed using flow cytometry, a sensitive method for detecting particles as tiny as viruses.

The gut microbiome can affect cognitive ability, metabolism, weight gain or loss, and mood, researchers said. It can also cause inflammation that could lead to cancer, diabetes, Crohn's disease, and irritable bowel syndrome. With careful analysis and planning, food could be used as medicine to correct imbalances, according to the study.

While other studies have focused on increasing the abundance of therapeutic phages, this research goes further to explore the reductive effect of 117 commonly consumed foods, chemical additives, and plant extracts on the growth and phage production capacity of common gut bacteria.

Conversely, over-consumption of broad-spectrum antimicrobial foods could contribute to the same metabolic states correlated with low gut diversity that may be produced by the administration of antibiotic medicines. Proper understanding and utilization of these food compounds could aid in the treatment or prevention of conditions associated with gut imbalances and promote overall health.

The researchers recommend that foods found to be prophage inducers should be studied further to elucidate their molecular mechanisms. While the importance of phages and the fact that they are the most prolific biological entity in the biosphere is well-established, little is understood about the triggers that cause bacteria to produce phage and release them into the environment. Elucidating these mechanisms will further our understanding of how bacteria and phage shape the ecosystems that they populate, the researchers said.

"We are excited about finding more prophage inducers and determining the molecular mechanisms by which they work,” said Forest Rohwer, one of the study’s authors and microbial ecologist at the university. "There are probably thousands of compounds that would be useful for eliminating unwanted bacteria."