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Molecules Produced by Gut Bacteria Extend “Healthspan”

Researchers have discovered that a class of molecules produced by friendly gut bacteria could extend the time that worms, flies, and mice remain healthy during their lives—with potential implications for human health. Advances in research and health care have contributed to people living longer, particularly those in developed countries. However, associated with this longer lifespan is a decrease in “healthspan,” which is the length of time that a person is healthy and free of age-related illnesses. Finding ways to increase healthspan could reduce frailty and health care costs, while improving people’s quality of life. Thus, researchers were interested in identifying biological pathways that regulate healthspan independently of lifespan.

Gut microbiome composition changes with aging, but it is not known if the microbiome plays a role in regulating healthspan. To examine a potential link, researchers focused on a class of molecules, called indoles, produced by Escherichia coli (E. coli) and other bacteria found in the gut. (These bacteria include harmless types of E. coli.) They built on their previous research showing that indoles secreted by E. coli protected the roundworm Caenorhabditis elegans (C. elegans) from damage induced by stress, which is one component of healthspan. In new research, scientists examined the effect of indoles on other aspects of healthspan in the same animal model. To do this, they fed C. elegans strains of E. coli that either did or did not make indoles and measured markers of healthspan, such as motility, reproduction, and how well the worms swallow. They found that the presence of indoles did not have a significant effect on maximal lifespan, but did extend the healthspan of C. elegans. The scientists also studied whether indoles had a similar role in other animal models. Adult fruit flies lacking their own gut bacteria had greater ability to climb and were more resistant to heat stress when colonized with an E. coli strain that produced indoles compared to a strain that did not. Additionally, both young and old mice that had indole-producing E. coli in their guts showed improved measures of healthspan over a 3-month period. Together, these results suggest that indoles play a similar role in promoting healthy aging across different animal models. Further experiments showed that indoles exert these effects via cellular components called aryl hydrocarbon receptors, which are on the cell surface and bind to indoles and other small molecules to activate certain genes. The scientists showed that indoles regulated the activity of genes in C. elegans that were associated with healthspan but not lifespan, and exposure to indoles also shifted gene activity profiles in aged worms to reflect those of younger worms.

This research has identified a new role for gut bacteria: promoting healthy aging via the production of indoles. If the same results are observed in people, indoles or similar molecules represent possible therapeutics to increase healthspan. The researchers note that plants, such as kale and broccoli, also produce indoles. However, additional research would be needed to determine whether these sources of indoles would be potent enough for inducing the effects seen in this research study before the results can be translated into human therapy.

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