Behavioral Transplants

Twelve Canadian scientists accomplished something we've only heard about in science fiction: They transplanted a set of behaviors from one set of animals to another set of animals! And you'll never guess what part of these animals they physically transplanted to achieve this feat: It was not their brains; It was not their hearts; It was their gut-contents! We have all heard the phrase "you are what you eat", but scientists have discovered the real truth: You are what you poop.

Science is rapidly discovering that the intestinal tract is a vast ecosystem of microbes and the proportion of each microbe species present doesn't just influence digestion, but also brain development, cognition and even behavior. This connection has been termed the microbiota-gut-brain axis and is a new and quickly growing area of research. Different strains of lab mice are known to have different personalities: Some are more anxious and skittish, while others are more easy-going and friendly. When scientists looked at the microbes in their guts, they found that anxious mice and easy-going mice had different proportions of these microbial species. Different microbe species seem to have different effects on their hosts. While some gut microbes can cause illness, mice that have been raised so that they have never had any gut microbes have all kinds of problems, including symptoms of irritable bowel syndrome (IBS), obsessive compulsive disorder (OCD), depression, and autism, suggesting that some microbe species are important for healthy brain functioning.

Stephen Collins of McMaster University and his research collaborators tested the effects of gut microbes on behavior by giving BALB/c mice either 7 days of oral antibiotics or water. BALB/c mice are a very timid and anxious mouse strain. Normally, BALB/c mice that are placed in a box that is half dark and half bright will prefer to spend more time hiding in the dark side. BALB/c mice placed on an elevated platform will hesitate and take a long time to step down to explore. After a week of antibiotic treatment, mice given the antibiotic had a different proportion of microbe species in their guts, spent more time in the bright side of the light-dark box and were quick to step down from the elevated platform to explore! The scientists also found brain changes in these mice that correspond to decreased anxiety. But when the mice were tested a second time two weeks after treatment, all effects were gone, likely because the gut microbes were able to repopulate and rebalance their ecosystems.

The scientists then compared two specific strains of mice that are known to exhibit very different behaviors: BALB/c mice are more anxious, whereas NIH Swiss mice are more friendly and exploratory. As you would expect then, NIH Swiss mice typically spend more time in the light side of the light-dark box and step down from the elevated platform quickly, whereas BALB/c mice typically spend more time in the dark side of the light-dark box and take a long time to step down. The scientists transferred the microbial gut contents of the BALB/c mice to the NIH Swiss mice and vice versa. A week later, the normally outgoing and exploratory NIH Swiss mice were much more hesitant and anxious, whereas the normally anxious BALB/c mice were now very exploratory! They also found brain changes that correspond to increased anxiety in the NIH Swiss mice and with decreased anxiety in the BALB/c mice. Two weeks after that, the behavioral differences were still there, but the brain differences were not.

The fact that these differences may be long- or short-lived shows that there is likely an interaction between our genes and the ecologies of the microbial communities living within us. The behavioral effects of the microbial communities within us can be thought of as an "extended phenotype". They are heritable: Babies born by cesarean section have different microbes than those that are born vaginally and twins have more similar microbes than other pairs of siblings. However, they are also changeable: Simply eating yogurt, for example, seems to influence our gut microbes and behavior. For some illnesses, we are finding a dramatic positive effect of fecal transplants in people. As gross as it may sound, fecal transplants have had a clinical cure rate as high as 92% for recurrent CDI (an intestinal infection), compared to cure rates less than 31% by other methods. Although data is still scarce, fecal transplants have also shown promise for treatment of obesity, diabetes, multiple sclerosis (MS), Parkinson's disease, chronic fatigue syndrome, and autism. This field is still in its infancy and there is much we have yet to learn before this becomes a more widespread practice. Hopefully, the next question they answer is How do we make this less gross?

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Further reading:

Bercik, P., Denou, E., Collins, J., Jackson, W., Lu, J., Jury, J., Deng, Y., Blennerhassett, P., Macri, J., McCoy, K.D., Verdu, E.F., Collins, S. The Intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice, Gastroenterology, 141:599-609 (2011). DOI: 10.1053/j.gastro.2011.04.052.

Collins, S., Kassam, Z., and Bercik, P. The Adoptive transfer of behavioral phenotype via the intestinal microbiota: experimental evidence and clinical implications, Current Opinion in Microbiology, 16: 240-245 (2013). DOI: 10.1016/j.mib.2013.06.004.

Image Credits:

Lightmatter_lab_mice.jpg by Aaron Logan at Wikimedia Commons.