A team of scientists led by Premysl Bercik, Associate Professor of Medicine at McMaster’s Michael G. DeGroote School of Medicine, carried out two sets of experiments with mice with the goal of studying the effect of gut microbiota on behaviour in an established model of anxiety and depression.
Previous studies had shown that conventional mice subjected to maternal separation as pups developed altered stress responses, anxiety and depression-like behaviour in adulthood, as well as gut dysfunction.
First, researchers subjected mice to early life stress by separating the newborn pups from their mothers from days 3 to 21 for three hours every day and confirmed that the conventional mice with complex microbiota displayed anxiety and depression-like behaviour, as well as high levels of the stress hormone corticosterone. The animals also suffered from gut dysfunction (increased faecal pellet output), which scientists measured indirectly by assessing the release of the major neurotransmitter acetylcholine from colonic tissue, responsible for regulating motility and permeability, in vitro.
Then, they repeated the same experiment but this time with germ-free mice, lacking any gut microbiota. Those rodents also presented altered stress hormone levels and gut dysfunction, but, in contrast, did not show any signs of anxiety or depression. “Our results suggest that the bacteria are required for the induction of anxiety and depression in this mouse model,” Bercik, co-author of the study with postdoctoral fellow Giada de Palma, told Gutmicrobiotawatch.org.
In the second set of experiments, they colonised germ-free control and germ-free maternally separated mice with normal healthy microbiota. Then they observed that the colonised control mice maintained the same microbiota, but the germ-free maternally separated mice developed distinct microbial profiles with different metabolic activity, which was associated with the development of anxiety and depression-like behaviour.
“Gut dysfunction and altered stress hormones in maternally separated mice shape the gut microbiota towards a specific phenotype that promotes anxiety and depression-like behaviour,” explains Bercik. “This shows that both the host – the mouse – and microbial factors are required for the induction of the altered behaviour in this model.”
The results of this new study throw light on the understanding of how gut microbiota can shape host behaviour. It would be important to determine whether this also applies to humans. “Many studies in humans showed that early life stress, in the form of neglect or abuse, can lead to psychiatric disorders later in life. This is likely through the impact on the neural system, which is very plastic in early life,” says Bercik.
If these results were confirmed in humans, treatment with probiotics or specific diets could be useful in preventing or improving the consequences of early life stress.
Bercik and his team had previously shown in 2011 that bacteria can change exploratory behaviour in a study with healthy mice that were administered non-absorbable antibiotics and which became more daring and active. Also, they demonstrated in a 2010 study that a specific probiotic B. longum improves inflammation-induced anxiety (also in rodents).