TMC PULSE

t m c » p u l s e | a p r i l 2 0 1 5 27 James Versalovic, M.D., Ph.D., the Milton J. Finegold Professor of Pathology at Baylor, pathologist-in-chief at Texas Children's Hospital and director of the Texas Children's Microbiome Center and Ruth Ann Luna, Ph.D., assistant professor of pathology at Baylor and director of medical metagenomics within the Texas Children's Microbiome Center. "Through trial and error, I began making some changes to his diet, which turned out to be very signif- icant and explained a lot of the behavioral challenges. We're hoping this study will help shed a light on connections like this so that we can tailor treatment options to kids depending on their bacterial chemis- try. Ideally we can help treat their GI problems and in doing so, alleviate some behavioral issues that may be directly related." Luna is quick to note that despite there only being one clinical classification for autism, it is truly a spectrum disorder with varying degrees of severity. As such, treatment options for GI issues must be tailored depending on the child's clinical and behavioral symp- toms as well as their bacterial profile. "There is no such thing as one autism," said Luna. "There are several autisms and they are all different, so treatment is going to be different, too. A one-size-fits- all approach is not going to work." The first-of-its kind study will compare wide-rang- ing data related to gut bacteria, GI symptoms and behavioral issues to look for potential connections. It will analyze individual microbiomes—all of the bacteria and microorganisms present in the gut specimen—as well as the small biological molecules that can be isolated from that specimen, known as the metabolome, and use that data to evaluate metabolic disturbances in children with autism, identify any biomarkers of abdominal pain, and gain further under- standing of the gut-brain-microbiome axis. The gut-brain-microbiome axis refers to the biochemical signaling that occurs between the gas- trointestinal tract and the nervous system. Luna and Versalovic are working to identify the specific impact of the microbiome on the brain and how harnessing bacteria in the gut could not only alleviate GI symp- toms but potentially influence brain chemistry as well. "The enteric nervous system, which governs the gastrointestinal system, is a huge part of the nervous system. We have a very extensive network in the abdo- men and we have some evidence that the microbiome is signaling to the enteric nervous system and then also signaling to the brain and the central nervous sys- tem," Versalovic explained. "So as we fill in the gaps, because there are many gaps at this point, we are hop- ing to understand the specific links: microbes making neurotransmitters or signals that affect neurons, neurons firing in the peripheral nervous system, and that activity ultimately affecting the central nervous system of the brain." Luna added that because of the intrinsic intercon- nectivity between the enteric nervous system and the central nervous system, shifting the balance of one would have an impact on the other. "We think that by restoring gut health, we can perhaps repair some of the brain functions that may be damaged. The pathway goes in both directions. Certain bacteria are known to impact neurotransmitters, so it stands to reason that the right community can cause the brain to function more effec- tively, while the wrong community could definitely tax the system by causing too much inflammation or by blocking pathways that provide energy to fuel neurons. We're not saying we're going to cure autism, but we may be able to reduce behavioral symptoms as we're treating these gastrointestinal imbalances." Ultimately, Versalovic and Luna hope that studies like this will not only help researchers gain a more complete understanding of how the gut and the brain are connected, but also bolster new therapies based on microbiome science. "We're looking at medicine holistically, thinking about our microbial cells and human cells in tandem and using that knowledge to treat the whole human being," said Versalovic. "We need to do a better job of recognizing these microbes as a part of us and then enabling them to work for us, either by maintaining the microbiome if it's functioning well, replenishing the microbiome if it's depleted, or supplementing the microbiome in a way that improves health." If successful, these therapies could have applica- tions far beyond their initial objectives. "In the future we could be using information about the microbiome to help maximize brain development in infancy and early childhood, or maybe even influence human behavior in a positive way," said Versalovic. "This research project will enable us to establish a foundation so that we can continue to pursue these connections between the microbiome and the brain." To gather the most comprehensive research on this topic to date, Luna and Versalovic are currently recruiting children ages four through 12 with autism, with or without GI symptoms; unaffected siblings of children with autism; and children without autism, also with or without GI symptoms. The enrollment of healthy children with no symptoms is critical for the success of studies such as this for data comparison and analysis. The study is currently enrolling at three differ- ent sites including Baylor College of Medicine/ Texas Children's Hospital, The University of Texas Southwestern Medical Center in Dallas, and Nationwide Children's Hospital in Columbus, Ohio. It involves a commitment of about two weeks, a stool specimen collected at home for testing, and a series of surveys and diaries to be completed by the parents. For more information or to enroll in the study, please contact Dr. Luna at raluna@bcm.edu. LUNA AND VERSALOVIC ARE WORKING TO IDENTIFY THE SPECIFIC IMPACT OF THE MICROBIOME ON THE BRAIN AND HOW HARNESSING BACTERIA IN THE GUT COULD NOT ONLY ALLEVIATE GI SYMPTOMS BUT POTENTIALLY INFLUENCE BRAIN CHEMISTRY AS WELL.

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