Early life stress implications on the gut microbiome

A growing body of evidence supports the significance of the gut microbiome with respect to behavioral disorders, as mediated by disruption to the gut-brain axis.  Importantly, there is a lack of understanding regarding associations between gut microbiome dysbiosis and behavioral phenotypic outcome.  Traumatic childhood events early-in-life can result in later-in-life behavioral consequences.  Maternal separation (MS) is an example of such an event that is represented with a well-established preclinical (i.e., animals) experimental model for early life stress.  In a recent study, researcher’s sought to investigate the precise role of MS in the induction of changes to the gut microbiomes of mice, and the potential behavior phenotypic consequences brought on by these changes. 

C57 mice were subject to three unique experimental groups: germ-free (GF) mice, specific pathogen-free mice (SPF, i.e. mice with microbiome compositions), and germ-free mice that were eventually subject to recolonization.  Mice were either left alone after birth or exposed to MS 3 days after birth.  Behavior was examined after 8 weeks, and the germ-free group was sacrificed after 9-10 weeks and the SPF group after 16-20 weeks.  The recolonization group was recolonized with microbiota at 12-13 weeks, followed by more behavioral tests and subsequent sacrificed. 

Corticosterone - a major stress hormone - was significantly elevated in both GF and SPF mice that were subjected to MS.  The researchers next wanted to define a relationship between the host microbiome and anxiety-like behaviors weeks after being separated from the mothers.  It was fist observed that MS did indeed alter microbiota composition in SPF mice.  Interestingly, MS-induced anxiety like behavior was observed in SPF mice, but not in GF mice, suggesting that the microbiome played a significant role in the development of these types of behaviors.  The experimenters then recolonized the guts of a subgroup of GF mice.  Indeed, behavior was altered in MS mice whose guts were colonized as compared to the MS mice that remained germ free.  Other physiological indicators demonstrated significant interactions between MS and the presence of gut microbiota, as gut microbiota presence had a significant impact on noradrenaline and serotonin levels. 

All told, the findings in this study suggest microbiome dysbiosis is a critical physiological driving force behind the behavioral phenotypes associated with early life stress events.  It will next be important to begin thinking about translate these preclinical findings in a clinical setting, in hopes of exploring ways to help those in need.

The microbiome may affect a child’s temperament

A new study was recently published that highlights the gut-brain axis once again.  The study, out of Ohio State University and published in Brain, Behavior, and Immunity, compares the microbiomes of toddlers and compares it to their overall behaviors.  The results show an association between temperament and the microbiome may exist.

In the study 77 toddlers were recruited to take food questionnaires, behavioral tests, and have their stools sampled.  They discovered that certain microbiome differences, which were not attributable to differences in diet, were directly associated with behavioral traits.  Chief among them was the discovery that higher microbiome diversity was correlated to more extraversion in children.  Whether or not this microbiome difference is the cause, or an effect, of these children being more active and engaged with their environments is still unknown.  Another connection was that Rickenellaceae was associated with fearful female toddlers and high intensity male toddlers.   This was interesting because bacteria from this genus have been associated with depression.

We note that the researchers’ testing methods were hardly rigorous due to the lack of controls, but the gut-brain axis has been well established, so this work still fits into an existing framework.  In addition, some may be skeptical that the microbiome could be influencing children’s behavior, but remember that the bacteria within us have been evolving along with us for so long that nothing should surprise us.  The next time the parents out there are dealing with their unruly children, you can kill two birds with one stone by punishing them by making them eat sauerkraut or kimchi!

The microbiome and autism

I want to discuss a really important paper from December 2013 published in Cell by the Mazmanian lab at Cal Tech that links the microbiome to autism spectrum disorders (ASD).  We already know that there is link that is becoming well-established between the gut and behavior.  It has also been shown by other researchers that humans with autism also have high levels of IBD and other intestinal disorders.  This suggests microbiome dysbiosis may be linked to autism, and was the motivation for this research.

In the paper the researchers induced ASD symptoms in mice by using a known method in which  a mother is infected with a virus-like molecule, and the offspring of that mouse have a high likelihood of having ASD symptoms.  After doing this procedure they directly demonstrated that those mice with ASD symptoms had reduced GI tract integrity, and had elevated levels of some metabolites in their blood when compared to offspring mice from the same mothers without ASD symptoms.  Furthermore, some of the metabolites that were elevated are thought to be biomarkers for autism in humans (they are also elevated in humans with autism).  Finally, when the offspring mice with ASD symptoms were given a probiotic, their symptoms were reduced, and those same metabolites were also reduced.  

This research is especially exciting given that the probiotics were therapeutic for mice already displaying ASD symptoms, suggesting a possible cure for autism, but obviously let's not get ahead of ourselves. 

A nice round-up of the article, which was co-authored by our friend Rob Knight, has a great summary of research, and I suggest anyone with further interest to read it.

The gut-brain axis - microbiome and depression

Today I will be discussing a review from a little more than a year ago that discusses research that links the microbiome with stress, anxiety, and depression.

First, it should be noted that a 2-way communication between the gut and brain has already been established.  The review goes on to mention studies in mice where not only are germ free mice associated with higher stress responses, but stress and anxiety early in life are associated with long-term changes in the microbiome.  There was efficacy in reducing stress by treating stressed mice with probiotics.  Other studies however have shown germ-free mice to have reduced stress when compared to their counterparts.  In addition, multiple studies showed that inflammation of the gut caused by dysbiosis or a pathogenic gut bacteria increased stress and anxiety levels in mice.

There are many mechanisms by which the microbiome communicates with the brain and may affect the stress levels.  I encourage anyone interested to read the paper to learn more.  In the end, more research is needed to discover just how important the microbiome is to our mental health.