BY: Stephanie Thomas, PhD
DATE: September 1, 2016
The big buzz in research these days is “Microbiome”. It has even caught the attention of the White House. On May 13th of this year, President Obama and the White House Office of Science and Technology Policy announced the National Microbiome Initiative to support microbiome research in various ecosystems, from human microbial populations to soil and aquatic environments. This $121 million Federal investment highlights the interest in this important field and the magnitude of research questions yet to be answered.
First, we need to clarify terminology. A microbiota is a consortium of microorganisms consisting of bacteria, viruses, archaea, and fungi that have evolved to live cooperatively in a particular ecosystem. The microbiome is all the genes associated with a given microbiota. In animals, including humans, the intestinal microbiota has evolved to live symbiotically with its host—the microbial population is able to capitalize on the nutrient rich environment supplied in the gut while offering its host (you!) an array of benefits. The bacteria in your gut have their own metabolism and products of that metabolism include vitamin production, fermentation of foods that you can’t digest, as well as healthy development of your intestinal tract, absorption of nutrients from the food you eat, fat distribution, and much more. The gut microbiome of an individual is influenced by diet, geography, genetics, age, and other factors. Although each individual harbors a unique microbial signature (like a fingerprint, only in this case a “bug-print”), a common “core” gut microbiome exists across individuals consisting of similar populations of certain microbial families (Qin et al., 2010). Given the numerous benefits of the intestinal microbiome, it is believed that disruptions in the microbial population (also referred to as dysbiosis) could alter the host’s physiology and lead to or contribute to disease. The opposite is also true, host diseases could disrupt the microbiome which in turn further contributes to the diseased state.
We are constantly discovering more about the gut microbiome. One new discovery is the influence of gut microbes on mood and behavior. The bi-directional communication between the gut and the brain (coined the “gut-brain axis”) is of particular interest. Although the tight-knit association between the gut and the brain has been surmised for centuries (e.g., “trust your gut” and “gut instincts”), research is now revealing that the microbiome does indeed influence behavior via the gut-brain axis. For example, establishment of an intestinal microbiota is important in the development of the hypothalamic-pituitary-adrenal axis, which regulates processes such as the stress response, digestion, mood, and energy expenditure (Sudo et al., 2004). Other studies have shown that individuals with gastrointestinal diseases, such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), harbor a disrupted gut microbiota and individuals with these illnesses report higher levels of anxiety, stress, and depression (Moloney et al., 2016; Neuendorf, Harding, Stello, Hanes, & Wahbeh, 2016; Ott & Schreiber, 2006). Currently it is not well understood how the microbiome gains access to this communication system. Research is now focusing on this question, as well as which alterations in the microbiome can influence mood and behavior. For reviews on this topic see the following publications, (Bauer, Hamr, & Duca, 2016; Cryan & Dinan, 2012; Luna & Foster, 2015).
Communication within the gut-brain axis can also play a role in eating disorders. A recent investigation by Kleiman and colleagues at UNC (Kleiman et al., 2015) found that reduced gut microbial diversity in individuals with anorexia nervosa was significantly associated with self-reported depression, anxiety, and eating disorder symptoms. This research suggests that disturbances in the gut microbiota is enhancing and reinforcing the psychological symptoms associated with this disease. Ongoing research in the labs of Ian Carroll and Lisa Tarantino at UNC will further investigate these observations in germ-free rodent models. Germ-free rodents are born and reared in a sterile “bubble” and are free of microorganisms. The germ-free rodents are essentially a blank slate with which to study the effects of different microbiotas. The investigations by Carroll and Tarantino will transplant fecal microbiota from individuals diagnosed with anorexia nervosa or healthy controls into the intestines of germ-free rodents. After transplant, the rodents will be tested for differences in behavior and other physiological symptoms typically associated with the disease to better understand whether they are linked to changes in the gut microbiota.
Previous rodent studies have, in fact, reported differences in behavioral tests based on the presence or absence of a microbiome (Cryan & Dinan, 2012). A recent study by Kelly and colleagues (Kelly et al., 2016) investigated whether depression could be acquired through fecal microbial transplants. Similar to the approach used by the Carroll and Tarantino labs, fecal samples from clinically depressed individuals or healthy controls were transplanted into the intestines of rodents depleted of its normal microbiota by long term exposure to antibiotics. The rodents were then tested for various changes in behavior and physiological symptoms. The results showed a significant increase in depressive-like behavior in the rodents receiving the fecal samples from the clinically depressed individuals. These findings are important in that they confirm that the gut microbiome can transfer depressive-like behaviors to a recipient.
So, how does this study relate to eating disorders research? If the observations underlying the study are generalizable, it suggests that an anorexia nervosa adapted microbiome can potentially perpetuate the psychopathology of the disease. Research underway in the Carroll and Tarantino labs is examining this possibility and will determine if the gut microbiome from individuals with anorexia nervosa can transfer psychological symptoms such as anxiety and depression to germ-free mice. Of course, this is the first step, the next phase is to pinpoint the mechanisms by which the gut microbiome can alter mood and behavior, which could guide the development of adjunct therapies to assist with recovery from anorexia nervosa.
Bauer, P. V., Hamr, S. C., & Duca, F. A. (2016). Regulation of energy balance by a gut–brain axis and involvement of the gut microbiota. Cellular and Molecular Life Sciences, 73(4), 737-755. doi:10.1007/s00018-015-2083-z
Cryan, J. F., & Dinan, T. G. (2012). Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci, 13(10), 701-712. doi:10.1038/nrn3346
Kelly, J. R., Borre, Y., C, O. B., Patterson, E., El Aidy, S., Deane, J., . . . Dinan, T. G. (2016). Transferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the rat. J Psychiatr Res, 82, 109-118. doi:10.1016/j.jpsychires.2016.07.019
Kleiman, S. C., Watson, H. J., Bulik-Sullivan, E. C., Huh, E. Y., Tarantino, L. M., Bulik, C. M., & Carroll, I. M. (2015). The Intestinal Microbiota in Acute Anorexia Nervosa and During Renourishment: Relationship to Depression, Anxiety, and Eating Disorder Psychopathology. Psychosom Med, 77(9), 969-981. doi:10.1097/psy.0000000000000247
Luna, R. A., & Foster, J. A. (2015). Gut brain axis: diet microbiota interactions and implications for modulation of anxiety and depression. Curr Opin Biotechnol, 32, 35-41. doi:10.1016/j.copbio.2014.10.007
Moloney, R. D., Johnson, A. C., O’Mahony, S. M., Dinan, T. G., Greenwood-Van Meerveld, B., & Cryan, J. F. (2016). Stress and the Microbiota-Gut-Brain Axis in Visceral Pain: Relevance to Irritable Bowel Syndrome. CNS Neurosci Ther, 22(2), 102-117. doi:10.1111/cns.12490
Neuendorf, R., Harding, A., Stello, N., Hanes, D., & Wahbeh, H. (2016). Depression and anxiety in patients with Inflammatory Bowel Disease: A systematic review. J Psychosom Res, 87, 70-80. doi:10.1016/j.jpsychores.2016.06.001
Ott, S. J., & Schreiber, S. (2006). Reduced microbial diversity in inflammatory bowel diseases. Gut, 55(8), 1207.
Qin, J., Li, R., Raes, J., Arumugam, M., Burgdorf, K. S., Manichanh, C., . . . Yamada, T. (2010). A human gut microbial gene catalogue established by metagenomic sequencing. Nature, 464. doi:10.1038/nature08821
Sudo, N., Chida, Y., Aiba, Y., Sonoda, J., Oyama, N., Yu, X. N., . . . Koga, Y. (2004). Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J Physiol, 558(Pt 1), 263-275. doi:10.1113/jphysiol.2004.063388
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