Researchers have identified how lactobacilli, members of our gut microbiome, influence a key immune system protein, thereby affecting stress levels and mental health. These findings could lead to new ways to prevent and treat depression and anxiety using specially formulated probiotic supplements.
The connection between the gut microbiome and the brain has become a key area of research into mental illness. Studies have shown that disruption of the gut microbiome is associated with stress and mood disorders, and Lactobacillus is one of the bacterial families primarily reduced in such disorders. Lactobacilli are found in fermented foods such as yogurt, fermented vegetables (olives, kimchi, sauerkraut), salami and sourdough bread.
Early attempts to harness beneficial bacteria called probiotics to control gut microbes had mixed results, largely due to the overwhelming complexity of the microbiome, which is estimated to include 39 trillion microorganisms. Researchers at the University of Virginia (UVA) used an uncommon technique to study the mechanisms of how lactobacilli affect mental health.
Alban Gaultier, one of the corresponding authors of the study, said: "We know from previous studies that lactobacilli are beneficial in improving mood disorders and disappear after psychological stress, but the underlying reasons remain unclear, mainly due to the technical challenges of studying the microbiome."
To circumvent these technical difficulties, the researchers used a consortium of eight bacterial strains, including two strains of Lactobacilli, called Altered Schaedler Flora (ASF). Microbiology is the study of organisms in which each species of bacteria is tightly controlled.
They exposed mice to two random mild stressors every day for three weeks, disrupting their microbiota and reducing levels of lactobacilli. To determine whether a disrupted microbiome is a marker or trigger of anxiety- and depression-like behaviors, the researchers transferred the microbiota of stressed mice to germ-free mice, or mice without microbes in their bodies. They found that these behaviors were transferred along with the microbiota, suggesting that bacterial transfer is sufficient to drive behaviors associated with mood disorders and exposure to environmental stress.
To understand how this happens, the researchers conducted a metabolomic study of the serum of mice exposed to stressed microbiota. The only cytokine (a protein secreted by immune system cells) that changed significantly was interferon-gamma, which was reduced in these mice. Gamma interferon is essential for innate and adaptive immunity to protect against viral and certain bacterial infections.
Using either unchanged ASF or ASF removed from both Lactobacillus strains, the researchers created mice with and without the bacteria to explore whether it was responsible for altered interferon-gamma production. Both groups of mice were exposed to the stressor, and their brains were subsequently analyzed. Overall, Lactobacillus -negative mice had increased neuronal activation in brain regions associated with fear and anxiety compared to Lactobacillus -positive mice.
Fresh groups of Lactobacillus -positive and -negative mice underwent stress training for two hours per day for seven days. It was found that only mice without Lactobacilli were more susceptible to the effects of stress. Measurements before and after stress showed that lactobacilli-negative mice had lower concentrations of gamma interferon than positive mice, suggesting that in the absence of this protein, the mice are more susceptible to environmental stress. Mice injected with interferon-gamma neutralizing antibodies appeared to have a stronger response to acute stress.
The researchers say their findings provide a new framework for understanding the role of the gut microbiome and immune system in mood disorders.
"With these results, we have new tools to optimize probiotic development, which will accelerate the discovery of novel treatments," said Andrea Mercchak, first and corresponding author of the study. "Most importantly, we can now explore how to maintain healthy levels of lactobacilli and/or interferon-gamma to prevent and treat anxiety and depression."
The research was published in the journal Brain, Behavior, and Immunity.