Chris Christiansen

Gut-Brain Axis

As the Old Adage Goes

With recent progress made in research the old adage of “trust your gut” has taken on new meaning. The link between our microbiota and brain is irrefutable. This connection from the microbiota of our gut to our brain is responsible for a myriad of mental illnesses, structural changes, and physiological changes in our body. The exploration of these studies shows that gastrointestinal health effects the nervous system and the nervous system has direct effects on the gastrointestinal system, and that the two combined form a sort of symbiosis that can have negative and positive effects on one another.

     Cesarean sections make up 32.3 percent of all deliveries in the US according to the CDC. The US performs more C-sections than any other developed nation. With this comes certain risks and downsides which contribute to the high infant mortality rate. This mortality rate however is not the risk I will be focusing on. A normal delivery takes the fetus from the womb through the vaginal canal. The infant is then coated in a plethora of new microbiota from the mother's vaginal canal.

This unpleasant sounding process however contributes greatly to the microbiota found developing in the child hours later. Much of the child immune system come from the exposure to these maternal bacterial cells. Children who are delivered via C-section are not exposed to the same amount and type of bacteria as are the children who are birthed vaginally. However maybe the most interesting new finding comes out of Yale. A study performed at Yale University found that mice delivered via C-section had significantly less mitochondrial uncoupling protein 2 or (UCP2). This protein allows for the proper development of the hippocampal regions of the brain and the behaviors that are associated with that region. The researchers of this study hypothesized that the microbiota inherited from the vaginal delivery process aides in the formation and proper function of the UCP2 protein. Without this protein the research found that impairments developed in the rats due to the decreased amount and lack of functionality of the UCP2 proteins. This shows a direct correlation to the microbiota of the gut and the formation of proteins in the brain. This link would suggest that the “convenience” of C-sections might not outweigh the neural consequences it may invoke upon the infant.

     Another old adage, “you are what you eat” may also take on more meaning thanks to a study that took a look at the effects that “germ free” food had on the neural patterns of rodents. In this study there were three sets of rodents involved in the study. A control, a germ free population, and a specific pathogen free population. It was found that the germ free and specific pathogen free populations of rodents had an exaggerated stress response. This involved increased plasma corticosterone and adrenocorticotropic hormone levels in response to restraint stress, Simon (2012). This continued on from about six weeks of age well into adulthood. The control which was fed regular food containing microbes showed no increased stress levels. The elevated chemical stress levels are the same chemicals that often lead to anxiety disorders in humans. Obviously this suggests that the microbiota of our intestines have some sort of effect on the structural formation and thereby the function of our CNS.

This study is quite pertinent in a day and age when the modern family has the ability to keep a home virtually dirt and germ free. The so called “clean” theory is gaining more and more momentum as brain-gut axis studies such as these are published. The more we protect children and adults for that matter from bacteria and harmful pathogens the more we could be depriving them of not only a healthy immune system but a healthy nervous system as well. Obviously throughout history it has been an uphill battle to fight against these mysterious pathogens, many of which has decimated entire populations. Now that we have the science and technology to prevent so many diseases we are seeing that there may be some sort of weird symbiosis between humans and infectious pathogens. So maybe that callous father or coach was right after all when they told you to “rub some dirt on it.”

The mapping of the human genome was a monumental project that had so many promising outcomes. This project has helped the human race to further their understanding of many genetic diseases. Unfortunately, this project did little to help us understand Schizophrenia. This mental illness which has been shown by a large genetics wide association study to have very strong ties to genetics has escaped the very best proclaiming solving scientists of our day. After the hundreds of millions of dollars invested into the discovery and research of the genetics of schizophrenia maybe it is time to look into the power of the microbiota of these mental ill individuals.

In reference to my first paragraph concerning C-sections a study performed in 2014 by T.G. Dinan et al. references the correlation between premature births and the significant occurrence of schizophrenia. They state that the increasing prevalence of C-sections in countries such as Brazil and China may contribute to the increasing numbers of schizophrenics in these countries. With C-sections occurring 2-3 weeks before full term and comprising more than 50% of all deliveries in these countries this should be an area in which researchers choose to delve.  There have been several studies published on C-difficile infections and the prevalence of Schizophrenia in premature neonates. These studies suggest there is a correlation between the lack of intestinal microbiota and the devastating mental illness schizophrenia. It is suggested that the microbiota structure is very much genetic and therefore tends to be more similar within families when compared with other families that do not exhibit such mental maladies.

With these facts in mind it has been suggested by the researchers that we keep in mind the studies performed on patients with peptic ulcer disease. It was thought initially that stress was the primary cause of these diseases. However, when monozygotic and dizygotic twins were studied it was found that due to the similarities in gut microbiota and family genes monozygotic twins which shared very similar microbiota structure tended to have increased occurrence of these ulcers. The same reasoning and argument could be used for those with schizophrenia. Obviously, schizophrenia is a much more complex disease than peptic ulcers and the analogy does not work straight across. This discussion and research do ask some very poignant questions about whether or not we are barking up the right tree.

The brain is the final frontier of medicine. It is largely unexplored and unknown. As we have seen from the studies referenced above the brain is not an isolated organ system that controls all the other functions of our body. The nervous system is directly affected by the type and quantity of the microbiota in the gastrointestinal system. Despite advances in nutrition and pathogen killing medicines we seem to be creating new types of illnesses in the human race. This symbiotic relationship that we have with bacteria seem to be an ever changing balancing act. As we come to understand the effects that the gastrointestinal system has on our neural functioning we can hopefully understand more about this final frontier and the many illnesses that are caused therein. As the old adage goes, “an apple a day keeps the doctor away” may still ring true, just make sure that apple has a little bacterium on it first. 

Citations

1.      Simon, Gabriel M. "Quantitative Assessment of the Impact of the Gut Microbiota on Lysine ε-acetylation of Host Proteins Using Gnotobiotic Mice." Proceedings of the National Academy of Sciences of the United States of America 109.28 (2012): 11133-1138. JSTOR. Web. 27 Oct. 2016

2.      Neu, Josef, and Jona Rushing. "Cesarean Versus Vaginal Delivery: Long-term Infant Outcomes and the Hygiene Hypothesis." Clinics in Perinatology 38.2 (2011): 321-31. Web.

3.      "Gut–brain Axis." Wikipedia. Wikimedia Foundation, n.d. Web. 27 Oct. 2016. <https://en.wikipedia.org/wiki/Gut%E2%80%93brain_axis>.

4.      Makin, Simon. "Massive Study Reveals Schizophrenia's Genetic Roots." Scientific American. N.p., 10 Oct. 2014. Web. 27 Oct. 2016. <https://www.scientificamerican.com/article/massive-study-reveals-schizophrenia-s-genetic-roots/>.

5.      Dinan, T. G., Y. E. Borre, and J. F. Cryan. "Genomics of Schizophrenia: Time to Consider the Gut Microbiome?" Molecular Psychiatry 19.12 (2014): 1252-257. Web.

6.      Ferraris L, Butel MJ, Campeotto F, Vodovar M, Roze JC, Aires J. Clostridia in premature neonates' gut: incidence, antibiotic susceptibility, and perinatal determinants influencing colonization. PLoS ONE 2012; 7: e30594.