How our gut microbiome could help reduce anxiety and its potential effects on the most common antidepressant and anti-anxiety medication.

Interactions between the gut and anxiety

Oftentimes, when we’re nervous or worried we feel it in our belly. We may feel nauseous or need to run for the bathroom. Am I right in thinking you’ve felt something like this before?

There’s a growing body of evidence out there about a bidirectional connection between the gut and the brain, the gut-brain axis. Gastrointestinal disorders and mental illness often occur hand in hand. It has been found that the rate of irritable bowel syndrome (IBS) and other functional gastrointestinal disorders was four times higher in people with anxiety than those who don’t have anxiety. The rate of anxiety was also five times higher in people with IBS than without.

The reason for this bidirectional relationship may lie within the microorganisms populating our gut, an important aspect of the gut-brain axis. Termed the microbiome, our gastrointestinal system houses thousands of bacterial, fungal, and protozoan species, as well as viruses. Currently, the majority of research involving the brain-gut axis is focused on cell lines and animal models. In mice, it’s been found that some bacterial species living in the gut are associated with poor social behaviour and social avoidance. These species include Lachnospiraceae and Ruminnococcaceae, two pro-inflammatory bacteria from the Clostridiales class.

Supplements comprising other bacterial species have been found to reduce these behaviours in both mice and humans. There’s growing evidence that particular gut bacteria including Lactobacillus, Bifidobacterium, andBacteroides may be related to anxiety symptoms.

A common anxiety drug and the gut-brain axis

Fluoxetine, also known as Prozac, is a drug most commonly used as an antidepressant. It can also be used to reduce anxiety symptoms and is one of the first drugs prescribed to treat the condition.

A common side effect – weight gain

Like all medications, fluoxetine may cause unwanted side effects, such as weight-gain. In fact, weight gain is one of the most common reasons for choosing to stop the drug or not taking it properly. Amongst others, one possible mechanism by which fluoxetine causes weight gain may be related to its antimicrobial effect on one particular bacterial strain, Lactobacillus.

Lactobacillus is a group of bacterial species commonly populating our gut that is thought to work in harmony with our digestive system. It has been found to be relevant to many health factors including the regulation of body weight. Numerous studies in both animals and humans have determined a close relationship between abundant Lactobacillus species, including Lactobacillus casei, Lactobacillus fermentum, and Lactobacillus johnsonii, and healthy weight maintenance.

Can Lactobacillus control fluoxetine’s common side effect?

In one study the body weights of two groups of mice were monitored over a 29-day period. One group was given fluoxetine dissolved in a saline solution, and the other given an equal volume of the saline solution alone. As well as gaining more weight on average than the control mice, the mice given fluoxetine were also found to have lower populations of Lactobacillus in their gut microbiome. Could there be a connection here? Could the depletion of Lactobacillus have something to do with the weight gain of fluoxetine-treated mice?

The proposed ability of Lactobacillus species to help modulate body weight might be useful to control the unwanted side effects experienced by people taking fluoxetine.

The data from a meta-analysis of intervention studies in humans and animals, as well as two observational human studies, suggests that taking Lactobacillus probiotics may help moderate weight. In the meta-analysis, particular species of Lactobacillus, including casei, plantarum, and gasseri, were found to reduce obesity.

Although these studies suggest a connection between particular Lactobacillus populations and weight regulation, clinical trials re required to establish effects in the context of treatment for anxiety with Fluoxetine. Clinical trials are so important because they could help confirm the therapeutic effects of Lactobacilli in humans that have so far predominantly been observed in mice.

Lactobacillus and serotonin

There is another tantalizing reason to be interested in Lactobacillus: it may actually improve the effectiveness of fluoxetine. Fluoxetine works primarily by increasing the availability of serotonin in the brain, which you might know as the “happiness hormone”. Serotonin has other important functions, including regulating circadian rhythms and helping with sleep, improving memory, and influencing digestion.

At least one in-vitro study has examined the possibility that the species Lactobacillus salivarius possesses the same transporter found in neuronal cells associated with serotonin uptake. This investigation focused on the uptake of serotonin-like fluorescent molecules into Lactobacilli salivarius cell cultures. The results indicated that such transporters do exist, but more research using real serotonin in animals and humans is needed. Studies show that fluoxetine and other SSRIs have antimicrobial effects, demonstrating that there are interactions between the gut microbiome and antidepressants in both directions.

Anxiety-modulating properties of Lactobacillus

There are also studies suggesting that Lactobacillus could have its own anxiety-reducing properties. A common theme amongst stressed, anxiety-ridden mice is that they were found to have low Lactobacilluspopulations, and that their symptoms improved with administration of the bacterium.

So at least we know how to deal with mouse anxiety! What about humans? The administration of a Lactobacillus helveticus and Bacteroides longum combination probiotic saw improved psychological symptoms in humans and a decrease in the stress-related hormone, cortisol.

A recent meta-analysis cusing on human studies between 2017 and 2019 examined the potential anxiety-modulating effects of multiple probiotics. Of 24 trials examining Lactobacillus’ effect on anxiety, 22 saw reduced anxiety symptoms at the end of treatment compared to placebo controls.

A randomised, placebo-controlled human trial saw a reduction in stress-related symptoms after the daily consumption of Lactobacillus plantarum for 8 weeks. Another study determined that Lactobacillus rhamnosus significantly reduced depression and anxiety symptoms in women who had recently given birth. In a similar study, anxiety symptoms were alleviated in 39 chronic fatigue patients receiving Lactobacillus casei.

The body of knowledge surrounding anxiety, fluoxetine, and Lactobacillus suggests that a close connection exists and that Lactobacillus could help people taking fluoxetine in more ways than one. The bacteria could help reduce anxiety symptoms, reduce the weight-gain side effect, and maybe even increase the absorption of serotonin! More research is still needed to properly understand the bacterium’s potential, as many of the studies thus far have focused on mice.

While we obviously need more human clinical trials of lactobacillus and SSRIs combined, it’s possible that probiotics will one day be recommended alongside medications to better treat disease and to decrease potential side effects. 


Image by: Bob Blaylock / CC BY-SA

Dr Amy Loughman is a Postdoctoral Research Fellow at The Food & Mood Centre and leads the microbiome research stream. Her research aims to uncover the role of the human microbiome in brain function and mental health across the lifespan.

Mary Neylan is on an internship with The Food & Mood Centre whilst completing a degree in biomedical science at Deakin University. Mary’s research interests include neurology and found working on this article to be fascinating and worthwhile.