One specific species of bacteria may help reverse autism-like symptoms in mice

A new study links autism-like social behaviors in mice to the absence of a single species of bacteria [1]. What’s even more interesting is that the study authors were able to reverse some of the mice’s behavioral deficits by restoring those bacteria in the guts of the affected mice.

What’s the link between the gut and the brain?

Although this may sound like a new concept, the idea that our gut’s health influences our mental health dates back more than 100 years ago. It is now known that the gut and the brain communicate with each other via the gut-brain axis in a bidirectional manner: the brain influences gastrointestinal and immune functions involved in shaping the gut’s microbiome while bacteria in the gut produce neuroactive compounds such as neurotransmitters that act on the brain. For instance, research indicates that gut microbes stimulate the host’s intestinal cells to produce the neurotransmitter serotonin [2].

Since an imbalance in serotonin can influence mood and cause depression, it comes as no surprise that an unhealthy gut can cause behavioral issues and symptoms of depression. In fact, research indicates that probiotics can help ward off depression [3].

The study details

To better understand the relationship between ASD, maternal obesity and the microbiome, the researchers kept female mice either on a high fat diet or on a regular one (the control group, RD) for eight weeks. The high-fat diet consisted of 60% calories from fat whereas the regular one contained 57% calories from carbohydrates and 13.4% calories from fat. The researchers then allowed the mice to mate and produce offspring which were fed a regular diet after weaning.

Assessing the link between social interaction and the maternal diet

Numerous recent studies indicate that maternal obesity and an unhealthy maternal diet during pregnancy increase the risk of neurodevelopmental disorders such as autism spectrum disorders (ASD) in children. Since deficient social interactions are common behavioral issues in ASD, the researchers investigated the relationship between the prenatal diet and social behavior by assessing the following:

1. Reciprocal social interactions – the amount of time a pair of mice unfamiliar with each other spent interacting.
2. Sociability – the time mice spent interacting with an empty cage versus one containing a mouse.
3. Preference for social novelty – the time mice spent interacting with a familiar mouse versus an unfamiliar one.

Compared to the RD mice, the maternal high-fat diet (MHFD) offspring displayed social deficits including (i) fewer reciprocal social interactions, (ii) impaired sociability and (iii) no preference for social novelty.

Assessing the link between the prenatal diet, gut dysbiosis and autism

Gastrointestinal disorders are much more common in children with ASD than neurotypical children. This could be due to the less diverse gut microbiome in ASD children [4]. To determine whether maternal obesity during pregnancy and a high-fat prenatal diet can induce adverse changes in the offspring’s gut microbiome, the researchers analyzed the feces of the RD mice and MHFD offspring using rRNA gene sequencing. Compared to the control group, the MHFD offspring had less diverse bacterial communities indicating that an unhealthy diet can indeed affect the offspring’s microbiome.

Assessing the link between social impairment and the microbiome

Since mice eat each other’s feces, the researchers housed the socially impaired MHFD mice with the RD ones so that they would acquire microbiota from their cage-mates. Within four weeks, the behavior of the MHFD mice improved, indicating that the gut microbiome was restored.

To determine whether the effect observed was due to a beneficial bacteria species (and not simply co-housing), the researchers transplanted feces from RD mice and from MHFD offspring into germ-free mice. They found that the social behavior of the germ-free mice:

1. Improved when they received the transplant from the RD mice at 4 weeks but not at 8 weeks.
2. Remained impaired when the transplant came from the MHFD offspring irrespective of the time at which the transplant was carried out.

Assessing which bacterial species was affecting the mice’s social behavior

Using whole-genome shotgun sequencing, the researchers found that the MHFD mice had levels of Lactobacillus Reuteri that were nine times lower than those in RD mice. Levels of Lactobacillus Johnsonii were also reduced in the MHFD mice.

When the MHFD mice were given Lactobacillus Reuteri at 4 weeks, their sociability and preference for social novelty improved – similar treatment with Lactobacillus Johnsonii failed to improve the mice’s social behavior.

Why Lactobacillus Reuteri and where can you find it?

Lactobacillus Reuteri can help improve oxytocin levels, the ‘bonding’ hormone that plays a crucial role in social behavior [1]. In fact, senior author Mauro Costa-Mattioli says that “in response to social interaction, there was a lack of synaptic potentiation in a key reward area of the brain [of MHFD mice] that could be seen in the normal control mice. When we put the bacteria back in the maternal-high-fat-diet offspring, we could also restore the changes in synaptic function in the reward circuitry.“

Lactobacillus reuteri is found in many fermented foods including fermented dairy products, fermented meat products, and lactic acid fermented vegetables. You can also get it from supplements.

Does this mean pregnant women should avoid high fat diets?

Is this study suggesting a high fat diet is the problem? I don’t believe so. The study is showing how an important beneficial bacteria affect social behavior. Most beneficial bacteria require carbohydrates/fiber for colonization and proliferation. By having a diet high in fat and low in carbohydrates, the bacteria balance can shift negatively, causing low levels of important bacteria such as Lactobacillus reuteri.

The study did not indicate the types of fats used. Choose healthy fats such as grass-fed butter or clarified butter, virgin coconut oil, extra virgin olive oil, avocado and meats from grass-fed or pastured animals.

While an imbalanced diet can cause changes as seen in this study, I believe the important information to take away from this research is that beneficial bacteria, as well as dysbiosis play a powerful role in our health as well as our behavior and mood.  If you do well with a high fat diet but not starchy carbohydrates and grains, consider balancing the fat in the diet with other sources of fiber such as vegetables to meet your need to support bacterial species and levels.

References

1. Buffington, S. A., Di Prisco, G. V., Auchtung, T. A., Ajami, N. J., Petrosino, J. F., & Costa-Mattioli, M. (2016). Microbial reconstitution reverses maternal diet-induced social and synaptic deficits in offspring. Cell, 165(7), 1762-1775.

2. Yano, Jessica M. and Yu, Kristie and Donaldson, Gregory P. and Shastri, Gauri G. and Ann, Phoebe and Ma, Liang and Nagler, Cathryn R. and Ismagilov, Rustem F. and Mazmanian, Sarkis K. and Hsiao, Elaine Y. (2015) Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin Biosynthesis. Cell, 161 (2). pp. 264-276.

3. Dinan, T. G., & Quigley, E. M. (2011). Probiotics in the treatment of depression: science or science fiction?. Australian and New Zealand Journal of Psychiatry, 45(12), 1023-1025.

4. Kang, D. W., Park, J. G., Ilhan, Z. E., Wallstrom, G., LaBaer, J., Adams, J. B., & Krajmalnik-Brown, R. (2013). Reduced incidence of Prevotella and other fermenters in intestinal microflora of autistic children.PloS one, 8 (7), e68322.