Blog Post November 18, 2014

Microbiomes behavior and the intriguing link between gut and brain

As I wrote previously, the microbiome is emerging as a research area to be reckoned with. It has captured the public’s attention to significant degree as well, and the popular “overselling the microbiome” award, a watchdog effort of sorts that identifies hype beyond what the research actually shows, is still going strong, with a dozen more entries over the past year.

That there is a complicated and nuanced interplay between our microbes and ourselves is beyond doubt. Figuring out how it works and what it actually means for wellness and disease, however, is still in its very early stages. And recent reports of contamination problems introduced during sequencing indicate that the sequencing and analysis protocols still need refinement as well.

So it was without surprise that I saw the following headline online: Gut-brain link grabs neuroscientists. There have been many correlations made between gut microbiota and our mental states, some obviously spurious, others intriguing, albeit counterintuitive. It was a little surprising to see the headline in Nature News, however, generally one of the better places on the net to find accessible but unhyped science coverage. It’s a little depressing too. Our brains are already ridiculously complicated, and if they’re affected by our trillions of gut dwellers and all their genes and signaling chemicals, mechanistic understanding of behavior and psychiatric disorders will be that much more difficult to achieve.

But there it is in Nature News, saying the microbiome likely has an effect on mammalian brains, particularly early in life. Note the use of “mammalian,” as this work is being done in mice. Measurable behavioral effects have been measured in mice with different bacterial species in their guts and/or the presence of bacterial metabolites in their blood, with autism-like behaviors among those researchers are able to stimulate and reverse. It’s quite amazing, really, that just the presence or lack of Bacteroides fragilis, a bacterium usually common in the gut, will change a mouse’s behavior in significant ways.

Yet even the researchers seeking to demonstrate the validity of the effects admit that the “mechanism for these effects is still unclear.” And prospects for human mental health therapies are still quite remote. (Pro tip: At this point, microbiome “superfoods” and “supersupplements”—yes, some products are being marketed as such—have much more to do with making someone else money than improving your health.) So while the science is exciting in itself, the health implications for us are at best unclear when not oversold.

The implications for behavioral research using model organisms are profound, however. For the past century, inbred strains of mice have provided researchers the ability to reproduce experiments without genetic variables. But what if the genomes of model organisms such as mice are just the starting point, with the microbiome genes also playing a prominent role? Researchers at the University of Missouri noted a significant difference in the gut bacteria of mice from two different suppliers, one of them JAX. And the two mouse cohorts showed different behaviors as well, with the JAX mice showing more anxiety and stress markers in their blood. When they received bacteria from the non-JAX mice, the behavior differences ceased.

What does this mean? It’s certainly an important issue to address. Finding the biological mechanisms underlying complex behavior is a daunting task, but the prospects for success have never been better. The use of model organisms to investigate behavioral and psychiatric disease mechanisms has seen huge advances in recent years—advanced mouse populations, improved behavioral phenotyping capability, accurate genome sequencing and analysis, etc. The recent findings indicate that researchers need to be sophisticated not just in their choice and use of the mouse models themselves, however. They need to account for the whole world of microbiology in their guts as well.