Ingestion of Mycobacterium vaccae decreases anxiety-related behavior and improves learning in mice

Coevolution of microbes and their hosts has resulted in the formation of symbiotic relationships that enable animals to adapt to their environments and protect themselves against pathogens. Recent studies show that contact with tolerogenic microbes is important for the proper functioning of immunoregulatory circuits affecting behavior, emotionality and health. Few studies have examined the potential influence of ambient bacteria, such as Mycobacterium vaccae on the gut–brain–microbiota axis. In this preliminary research, we show that mice fed live M. vaccae prior to and during a maze learning task demonstrated a reduction in anxiety-related behaviors and maze completion time, when tested at three maze difficulty levels over 12 trials for four weeks. Treated mice given M. vaccae in their reward completed the maze twice as fast as controls, and with reduced anxiety-related behaviors. In a consecutive set of 12 maze trials without M. vaccae exposure, treated mice continued to run the maze faster for the first three trials, and with fewer errors overall, suggesting a treatment persistence of about one week. Following a three-week hiatus, a final maze run revealed no differences between the experimentals and controls. Additionally, M. vaccae-treated mice showed more exploratory head-dip behavior in a zero maze, and M. vaccae treatment did not appear to affect overall activity levels as measured by activity wheel usage. Collectively, our results suggest a beneficial effect of naturally delivered, live M. vaccae on anxiety-related behaviors and maze performance, supporting a positive role for ambient microbes in the immunomodulation of animal behavior.

► Mycobacterium vaccae-fed mice express fewer anxiety behaviors and faster complex maze run time.
► The effects of M. vaccae treatment in the complex maze lasted 8 weeks.
► M. vaccae treated mice showed more exploratory head dip behaviors in elevated zero maze.
► M. vaccae did not affect running wheel activity.
► Transient commensal bacteria may affect animal behavior via immunomodulatory mechanisms.