Bacteria and the anxious brain

Micah Manary has written a good summary of the recent Heijtz et al paper linking these two. The authors compared germ-free mice, which are raised in a completely sterile environment, and specific pathogen free mice, which are free of mice pathogens but otherwise have a normal gut microbiota, on a number of measures. First, the germ-free mice run more in an open field test, which is considered a sign of increased anxiety:

SPF = specific pathogen free = has bacteria in gut but no known mice pathogens; GF = germ free micel; top = distance traveled in the box per zone and in total over the 60 mins; bottom = representative tracings of movements in each group

Note the trend in the representative tracings, as the specific pathogen free mice tend to move less as time progresses, which is a sign that they are becoming “used to” the novel environment more quickly than the all germ free mice. Next, the authors conduct a number of gene and protein expression assays to show that there are statistically significant differences in various regions of the brain. For example, the germ-free mice have significantly reduced expression of the “early responder” gene nerve growth factor-inducible clone A:

open bars = normal gut microbiota but pathogen free mice; closed bars = germ free mice; OFC = orbital frontal cortex; AO = anterior olfactory region; left = representative autoradiograms

The authors used four mice in each condition, and some of the brain regions seemed to have significant expression trends for certain factors but not others. So we should take these results with the standard amount of caution. But the interaction between bacteria and the brain, especially during development, and especially related to anxiety, is certainly a trend to watch for in the coming years.


Heijtz RD, Wang S, Anuar F, Qian Y, Björkholm B, Samuelsson A, Hibberd ML, Forssberg H, & Pettersson S (2011). Normal gut microbiota modulates brain development and behavior. Proceedings of the National Academy of Sciences of the United States of America, 108 (7), 3047-52 PMID: 21282636