Ted Schettler, MD, MPH
An article in ScienceDaily titled “Mind-Altering Microbes: Probiotic Bacteria May Lessen Anxiety and Depression” begins with this lead:
Probiotic bacteria have the potential to alter brain neurochemistry and treat anxiety and depression-related disorders according to research published in the Proceedings of the National Academy of Sciences.
The journal reference is Javier A. Bravo, Paul Forsythe, Marianne V. Chew, Emily Escaravage, Hélène M. Savignac, Timothy G. Dinan, John Bienenstock, John F. Cryan. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proceedings of the National Academy of Sciences, 2011; DOI: 10.1073/pnas.1102999108. (visit the abstract)
This study in adult male mice shows alteration of GABA mRNA levels in the brain, reduced corticosterone levels, and behavioral changes associated with Lactobacillus treatment, mediated via the vagus nerve. The direction of changes in GABA levels varied in different brain regions. The authors are mainly concerned with measures of anxiety- and depression-related behavior.
But it strikes me that these findings may have broader implications. The gut-brain connection has been discussed among CHE partners in the past. Here is further evidence of changes in brain chemistry associated with altering the gut microbiome. But what might these findings imply for the developing brain? How might changes in GABA levels/receptors in response to gut flora influence brain development/function and autism risk, for example?
Here’s are several observations that I continue to wonder about:
The mode of delivery strongly influences microbial colonization of infants….including the gut (Dominquez-Bello, PNAS, 2010). Vaginally delivered infants acquire bacterial communities resembling mother’s vaginal microbiota dominated by Lactobacillus, Prevotella, or Sneathia spp, while C-section infants harbor bacterial communities similar to those found on skin, dominated by Staph, Corynebacteria, and Proprionibacterium spp.
Furthermore, studies of perinatal variables and autism risk identify C-section as a significant risk factor. Often, C-section is assumed to be a marker for some other pregnancy complication, but at least one study has identified ELECTIVE C-section as doubling the risk of autism (Glasson, Arch Gen Psych, 2004).
Why should elective C-section increase the risk of autism? Is it not plausible that the increased risk is related to altered gut flora and associated changes in brain chemistry?
It’s also worth noting that a recent review in the journal Science discusses the influence of the gut microbiome on development of the adaptive immune system. This is another mechanism by which altering the microbiome could influence autism risk. (Lee Y. Has the microbiota played a critical role in the evolution of the adaptive immune system? Science. 2010; 330(6012):1768-1773.)
Of course other factors, such as diet and antibiotic use, can also alter the gut microbiome. We’re learning more about the consequences as research in this area develops.
Earlier this summer, it was reported that S Korea has the highest autism incidence ever reported in a population (see http://articles.latimes.com/2011/jun/08/world/la-fg-korea-autism-20110608). Subsequently, I discovered that nearly 40% of children are born in S Korea by C-section…one of the highest percentages in the world (see http://www.who.int/healthsystems/topics/financing/healthreport/30C-sectioncosts.pdf). Yes, this is an ecological observation…and there may be no causal relationship between the two… Moreover, Korea may just be doing a better job of identifying children with autism than other countries. Still, I wonder when we will take a much closer look at the wisdom of increasing elective C-sections, as well as undertaking other interventions that can modify the gut microbiome, without better understanding the potential consequences.