Researchers Find Link Between Gut Bacteria and Depression

Bacteria in your gut play an important role in inducing anxiety and depression, scientists from the Farncombe Family Digestive Health Research Institute at McMaster University have discovered.

Their study, published today in Nature Communications, is the first to explore the role of intestinal microbiota in altered behaviour that comes from early life stress.

It has been known for some time that intestinal bacteria can affect behaviour, but much of the previous research has used healthy, normal mice, said Premysl Bercik, senior author of the paper and an associate professor of medicine with McMaster’s Michael G. DeGroote School of Medicine.

In this study, researchers subjected mice to early life stress by separating newborn pups from their mothers for three hours a day from the time they were three days old until they were three weeks old.

First, Bercik and his team confirmed that conventional mice with complex microbiota, which had been maternally separated, displayed anxiety and depression-like behaviour, with abnormal levels of the stress hormone corticosterone. These mice also showed gut dysfunction based on the release of a major neurotransmitter, acetylcholine.

Second, they repeated the same experiment in germ-free conditions and found that, in the absence of bacteria, mice which were maternally separated still have altered stress hormone levels and gut dysfunction, but they do not show any signs of anxiety or depression.

Third, they found that when the maternally separated germ-free mice were colonized with bacteria from a control healthy mouse, the bacterial composition and metabolic activity changed within several weeks, and the mice started exhibiting anxiety and depression.

But, if bacteria from stressed mice were transferred into non-stressed, germ-free mice, no abnormalities are observed. This suggests that in this model, both host and microbial factors are required for the development of anxiety and depression-like behavior.

“Neonatal stress leads to increased stress reactivity and gut dysfunction that changes the gut microbiota which, in turn, alters brain function,” said Bercik.

This image shows a man sitting against a wall. He is holding up a card with an unhappy face on it.
Researchers say this is another step in understanding how microbiota can shape behaviour, and that it may impact the field of psychiatric disorders. Image is for illustrative purposes only.

He said that with this new research, “We 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.”

Bercik said this is another step in understanding how microbiota can shape behaviour, and that it may impact the field of psychiatric 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 and depression,” said Bercik.

About this psychology research

Funding: This research was supported by grants from Crohn’s and Colitis Canada and the Canadian Institutes of Health Research.

Source: Suzanne Morrison – McMaster University
Image Credit: The image is in the public domain
Original Research: Abstract for “Microbiota and host determinants of behavioural phenotype in maternally separated mice” by G. De Palma, P. Blennerhassett, J. Lu, Y. Deng, A. J. Park, W. Green, E. Denou, M. A. Silva, A. Santacruz, Y. Sanz, M. G. Surette, E. F. Verdu, S. M. Collins and P. Bercik in Nature Communications. Published online July 28 2015 doi:10.1038/ncomms8735


Abstract

Microbiota and host determinants of behavioural phenotype in maternally separated mice

Early-life stress is a determinant of vulnerability to a variety of disorders that include dysfunction of the brain and gut. Here we exploit a model of early-life stress, maternal separation (MS) in mice, to investigate the role of the intestinal microbiota in the development of impaired gut function and altered behaviour later in life. Using germ-free and specific pathogen-free mice, we demonstrate that MS alters the hypothalamic–pituitary–adrenal axis and colonic cholinergic neural regulation in a microbiota-independent fashion. However, microbiota is required for the induction of anxiety-like behaviour and behavioural despair. Colonization of adult germ-free MS and control mice with the same microbiota produces distinct microbial profiles, which are associated with altered behaviour in MS, but not in control mice. These results indicate that MS-induced changes in host physiology lead to intestinal dysbiosis, which is a critical determinant of the abnormal behaviour that characterizes this model of early-life stress.

“Microbiota and host determinants of behavioural phenotype in maternally separated mice” by G. De Palma, P. Blennerhassett, J. Lu, Y. Deng, A. J. Park, W. Green, E. Denou, M. A. Silva, A. Santacruz, Y. Sanz, M. G. Surette, E. F. Verdu, S. M. Collins and P. Bercik in Nature Communications. Published online July 28 2015 doi:10.1038/ncomms8735

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