The above title is taken from a press release that coincided with the new article from John Cryan’s group at University College Cork, Ireland. In this case, “happiness” refers to the “happy hormone”, serotonin. Presumably this notion comes from the observation that SSRI medications boost serotonin levels and also elevate mood in some depressed people. (SSRI’s also alter immune cells, as do antipsychotic medications, but you’ll have to read my book to find out more about that topic) Getting back to this new paper, what they show is that germ free (GF) mice (born without bacteria and raised in a sterile environment) display less anxiety-like behavior (in a light-dark box test) than conventionally colonized (CC) mice. The latter are GF mice that were raised in a conventional cage setting where the mums and pups are exposed to the bacteria that normally inhabit that particular laboratory mouse colony. These bacteria are found on the skin, in the gut , respiratory tract, and the vagina. The observation that GF mice are less anxious has been made in a number of laboratories around the world (including our own), so this appears to be a robust finding. Since anxiety and stress are linked to serotonin, Cryan et al. measured this neurotransmitter in the brains (hippocampus) of GF and CC mice. It turned out that serotonin levels are higher in the GF males (but not in the GF females). This fits conveniently with the idea of a “happy” molecule alleviating anxiety and stress. It must be said, however, that behaviors related to actual depression (which is what SSRIs are normally used for) were not tested in this paper (those behavioral tests are described in my book). The differences between the sexes is interesting, although we have not seen this in our own studies, using a different strain of mice. In the converse experiment of adding back bacteria, some of the male GF pups were removed from the GF facility at the time of weaning, and placed in the conventional mouse colony and given bedding with fecal matter from CC mice. This results in bacterial colonization of the gut. Interestingly, this post-weaning colonization normalized the anxiety behavior (their movement in the light-dark box was similar to control mice), but it did not normalize the serotonin levels. That is, restoring the microbiota at the post-weaning stage decoupled the correlation between hippocampal serotonin levels and anxiety behavior. This suggests that the elevated serotonin in the GF mice was not driving their lack of anxiety. One might also ask, “What does the GF mouse model correspond to in human terms?” One case might be neonatal care units where preemies are raised, which, while relatively clean, the infants can still can contain bacteria if they came from a vaginal birth. There is also a recent paper providing evidence that fetuses are not totally germ free as was previously thought. Another human condition that might approximate GF status in the gut is repeated use of broad spectrum antibiotics, although this would be temporary. The most realistic mouse experiments, in human terms, involve manipulation of the types and numbers of specific bacteria in the gut, as has been done by my colleague Sarkis Mazmanian, for instance. This is what folks are trying to do when they take probiotic pills or various yogurts, etc. In prior posts, I’ve described mouse experiments in which manipulating the gut microbiome can very effectively prevent or ameliorate inflammatory bowel disease and even sepsis or a mouse model of multiple sclerosis!