The research used a combination of behavioral, molecular and computational techniques to test the role of the microbiota in depressive and ‘despair’ behaviors after noting that the fact that depressive disorders often run in families could – in addition suggesting a genetic component – point to the microbiome as a factor or causative agent.
"When you're stressed, you increase your chance of being depressed, and that's been known for a long, long time," said senior author Dr Alban Gaultier from the University of Virginia School of Medicine. "So the question that we wanted to ask is, does the microbiome participate in depression?"
Gaultier and his team used a mouse model to identify a biological process responsible for an effect on mood. Specifically, they found a reduced level of Lactobacillus and increased circulating kynurenine levels as the prominent changes in stressed mice.
“Surprisingly, therapeutic administration of L. reuteri to stressed mice improves metabolic homeostasis and corrects stress-induced despair behaviors,” said the team, writing in Nature’s Scientific Reports.
Based on this, they believe the findings should hold true in people, said Gaultier.
"The big hope for this kind of research is that we won't need to bother with complex drugs and side effects when we can just play with the microbiome," he commented. "It would be magical just to change your diet, to change the bacteria you take, and fix your health - and your mood."
Gaultier and his colleagues set out to understand whether and how microbiota alterations contribute to depressive symptoms and whether the gut microbiota could be therapeutically targeted to alleviate depression.
“We show that chronic stress significantly alters intestinal microbiota composition, primarily depleting the Lactobacillus compartment. ROS produced by Lactobacilli can inhibit kynurenine metabolism, a pathway that can negatively impact the brain when dysregulated,” said the team – who noted that when mice were exposed to stress they showed depressive symptoms and ‘despair behaviors’ alongside alterations to the makeup of their intestinal ecosyetsm.
“Restoring intestinal Lactobacillus levels was sufficient to improve the metabolic alterations and behavioral abnormalities,” the team said.
"A single strain of Lactobacillus (…) is able to influence mood,” commented Gaultier.
Primary researcher Ioana Marin said the changes seen are the most consistent the group has seen across a variety of experiments that profile the microbiome.
"This is a consistent change,” she commented. “We see Lactobacillus levels correlate directly with the behavior of these mice."
Gaultier was careful to reiterate that the symptoms seen in mice are ‘depressive-like behaviors’ or ‘despair behaviors’ – since mice have no way to communicate that they are feeling depressed.
However, the team noted that such symptoms are widely accepted as the best available model for looking at depression in creatures other than humans.
According to the team, the discovery could open the door to new strategies for treating depression as well as other conditions, such as anxiety.
Based on the new findings, Gaultier and his colleagues plan to begin studying the effect in people as soon as possible by testing the effects of Lactobacillus on depression in patients with multiple sclerosis – a group in which the disorder is common.
Promisingly, he noted that the same biological substances and mechanisms Lactobacillus uses to affect mood in mice are also seen in humans, suggesting the effect may be the same.
In addition to looking at the effects in people, the team also plan to continue exploring the role of kynurenine in depression and anxiety.
"There has been some work in humans and quite a bit in animal models talking about how this metabolite, kynurenine, can influence behavior," said Marin.
"It's something produced with inflammation that we know is connected with depression. But the question still remains: How? How does this molecule affect the brain? What are the processes? This is the road we want to take."
Source: Scientific Reports
Published online, Article number: 43859, doi: 10.1038/srep43859
“Microbiota alteration is associated with the development of stress-induced despair behaviour”
Authors: Ioana A. Marin, et al