Anxiety and depression caused by stress can be affected by whether or not gut bacteria is living in the intestines, scientists have found.
A study on laboratory mice has shown that anxious and depressive behaviour brought on by exposure to stress in early life appears to depend on microbes being present in the gut.
The researchers found that both stressed mice and stressed mice with no gut bacteria showed similar hormonal changes brought on by stress, but only the mice with gut microbes demonstrated the behaviour changes associated with anxiety and depression.
The study, published in the journal Nature Communications, demonstrated a clear link between gut microbiota – the microbes living naturally in the intestines – and the triggering of the behavioural signs of stress, they said.
“We have shown for the first time in an established mouse model of anxiety and depression that bacteria play a crucial role in inducing this abnormal behaviour,” said Premysl Bercik of McMaster University in Hamilton, Canada, the lead author of the study.
“But it’s not only bacteria, it’s the altered bi-directional communication between the stressed host – mice subjected to early-life stress – and its microbiota, that leads to anxiety and depression,” Dr Bercik said.
Previous research on mice has indicated that gut microbes play an important role in behaviour. For instance, mice with no gut bacteria – called “germ-free” mice – are less likely to show anxiety-like behaviour than normal mice.
The latest study looked at mice that had been exposed to a stressful experience in early life, such as newborn mice being separated from their mothers for a few hours each day over a period of three weeks.
When these mice grow up they display anxiety and depression-like behaviour and have abnormal levels of the stress hormone corticosterone in their blood, as well as suffering from gut dysfunction based on the release of the neurotransmitter acetylcholine.
But when germ-free mice with no gut bacteria are exposed to a similar stressful experience as newborns, they do not show any signs of anxiety or depression in later life even though they have similar levels of stress hormones in their blood and markers of dysfunction in their gut.
The scientists then transferred gut bacteria from the normal mice that had also been separated from their mothers to the “germ-free” mice so that their intestines became colonised with the same microbiota. Within a few weeks, the germ-free mice that had previously shown no signs of anxiety or depression started to display the same depressive, anxious behaviour as the ordinary mice that had been stressed during early life.
“However, if we transfer the bacteria from stressed mice into non-stressed, germ-free mice, no abnormalities are observed,” Dr Bercik said.
“This suggests that in this model, both host and microbial factors are required for the development of anxiety and depression-like behaviour. Neonatal stress leads to increased stress reactivity and gut dysfunction that changes the gut microbiota which, in turn, alters brain functions,” he said.
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The scientists believe that further research is needed before extrapolating the conclusions to humans to see whether potential therapies that target intestinal microbes can benefit patients with psychiatric or bowel disorders.
“It would be important to determine whether this also applies to humans. For instance, whether we can detect abnormal microbiota profiles or different microbial metabolic activity in patients with primary psychiatric disorders, like anxiety or depression,” Dr Bercik said.
“We are starting to explain the complex mechanisms of interaction and dynamics between the gut microbiota and its host. Our data show that relatively minor changes in microbiota profiles or its metabolic activity induced by neonatal stress can have profound effects on host behaviour in adulthood,” he said