Another microbiome perspective: The host holds the leash

Abstract depiction of the microbiome

Most scientists and clinicians accept that the human microbiome impacts a person’s nutrition, immune system function, physical health and perhaps even mental illness, but exactly how or why is not well understood. Now, taking an evolutionary approach, a Boston Children’s Hospital infectious disease researcher suggests the host may play a more active role in controlling the microbiome than previously appreciated.

“I think we need to re-evaluate the way in which we think about the microbiome,” says Seth Rakoff-Nahoum, MD, PhD, a physician-scientist at Boston Children’s in the Divisions of Infectious Diseases and Gastroenterology, whose perspective was published today in Nature.

“A host has quite a lot to gain by amplifying the beneficial traits of the microbiome while suppressing any exploitative or parasitic behaviors,” says Rakoff-Nahoum. “But how our body senses microbes as harmful or beneficial and how it selectively purges or encourages growth of certain strains is almost completely unknown.”

According to Rakoff-Nahoum, there are several strategies that humans might employ to control their individual microbiomes. These strategies could be as simple as the cognitive decision to avoid eating spoiled foods that may contain harmful microbes. Or, they may be as complex as the body having the remarkable ability to selectively target and kill harmful microbial strains or selectively encourage the growth of beneficial ones. One way to keep good microbes around might potentially be to “feed” them via the intestinal lining, allowing them to bloom and push out less helpful species.

The essential effect of these strategies, Rakoff-Nahoum says, would equate the microbiome to an ecosystem that the host keeps on a tight leash on.

Applying evolutionary theory to microbiome research

By looking at the microbiome as an ecosystem on a leash, Rakoff-Nahoum suggests that there may currently be too much emphasis on the importance of microbe-to-host effects rather than on host-to-microbe effects or even those of microbes to each other.

“Much the microbiota’s effects on the host may actually be the by-products of competition amongst the microbes themselves,” Rakoff-Nahoum says.

As a result, emerging therapeutics like fecal microbial transplant — which are meant to leverage the microbiome to improve the host’s health — have great potential to treat certain diseases, but Rakoff-Nahoum suggests that possible off-target effects should be carefully considered before interventions are made in such a complex ecosystem.

“If you need a real-life example of this, just look at the use of antibiotics and the subsequent rise of antibiotic-resistant bacteria,” says Rakoff-Nahoum.

Rakoff-Nahoum has long been interested in early life and the microbiome. In recent years, he took a comprehensive look at the innate immune system and gene expression of microbes in the intestines of mice at birth, after weaning and into adulthood. Read full story.

To better understand the relationship between microbiomes and their hosts, Rakoff-Nahoum and his team are developing experimental models for testing out their evolutionary theories about what gives rise to a microbiome’s form and function. One of the scenarios that Rakoff-Nahoum is investigating is early life and whether or not microbiomes are passed down through generations.

“Could there be a core, beneficial microbiome that transcends generations?” Rakoff-Nahoum wonders. “If so, how would the host to ensure not losing it?

“There’s something so dynamic about early life ­– analyzing this aspect of the host-microbiome relationship could help us understand not only the health of babies, but also potential later-life effects like diabetes, obesity and other types of disease,” Rakoff-Nahoum concludes.

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