Our early life microbiome may be more resilient than once believed

“We are inhabited by as many as ten thousand bacterial species… Together, they are referred to as our microbiome — and they play such a crucial role in our lives that scientists like Blaser have begun to reconsider what it means to be human.” ― Michael Specter

A couple weeks ago, I attended the Boston Bacterial Meeting where Martin Blaser gave the keynote address. Dr. Blaser, a physician and a microbiologist, studies the complex and often puzzling interactions between our bodies and our microbiome (the collection of microbes living on or in our bodies).

In his keynote address, Blaser spoke about the “disappearing microbiota” hypothesis where changes in human behaviors have altered the microbiome in such a way that certain diseases (such as obesity, asthma, and allergies) have become more prevalent. For instance, antibiotic use, cesarean sections, and formula feeding alter the microbiome of children early in life (see below).

Antibiotic use and obesity in animals

When antibiotics were used to treat sick animals, farmer had noted that adding low doses of antibiotics to livestock feed would promote their growth, particularly when they were given at a young age. Studies in mice have found that antibiotic exposure early in life resulted in an altered, less diverse microbiome that lead to metabolic perturbations that resulted in weight gain and impaired immunological development. These changes also occurred when the altered microbiome from one mouse was transferred to a germ-free mouse suggesting that these changes are dependent on the bacteria and not the antibiotics themselves.

Monitoring changes in gut microbiome in early life

On June 15, 2016, Science Translational Medicine published two papers on the early life microbiome:

(1) Researchers in Blaser’s lab analyzed the microbiome of 43 children for the first two years of life. Normally, intestinal bacterial communities undergo an age-dependent gradual succession that stabilizes after 3 years. The researchers observed three distinct phases in the early microbiome that is common among diverse human populations. The team also sought to determine how the early life microbiome is altered due to antibiotic use, cesarean section and formula feeding. Though the researchers found that these exposures delayed microbiome development and reduced species diversity, these disruptions were transient rather than permanent. These results differ from studies in mice where transient microbiome disturbances in early life had a lasting effect on the host.

(2) Ramnik Xavier’s research group at the Broad Institute investigated how multiple courses of antibiotics affect the early life microbiome. Like Blaser’s group, they found that antibiotic therapy correlated with a less diverse microbiome. Unlike what was shown in mice, repeated antibiotic exposure in children did not cause any weight gain. More significantly, these researchers found that antibiotic resistance genes were present in the microbiome after antibiotic treatment. Antimicrobial resistance genes present on bacterial chromosomes spiked in abundance shortly after treatment but then declined. Antimicrobial resistance genes present on mobile elements (such as plasmids) persisted much longer after antibiotic treatment. The origin of these genes in the microbiota is unclear, but their presence suggests a possible transfer of antimicrobial resistance genes from our microbiome to transient pathogens that may pass through our bodies.

So why the conflicting results between studies in mice and human? The link between antibiotics, microbiome and obesity may not hold for all animals. So far, it appears that antibiotics do affect the development of the early life microbiome but these changes may not be life-long in humans. Much of the microbiome research out there has taken a more descriptive approach instead of a functional approach (ex: what species are there vs. what the species are doing) and more insight may be gained by considering that different species within our microbiome may be functionally similar. Studies linking how our microbiome affects our development and physiology are just at their inception with many areas for exploration.