Using the Microbiome to Tackle Neuropsychiatric Disorders and Sleep Deprivation

    When thinking of the human body and its functions, one does not often imagine the stomach playing much of a role with the brain, let alone with neuropsychiatric disorders such as autism and schizophrenia. Contrary to popular belief, the gut uses a direct “axis” of communication to influence the brain called the gut-brain axis (GBA). According to current research, the GBA bidirectionally communicates through “multiple connections, including the vagus nerve, the immune system, and bacterial metabolites and products” (Rutsch et al., 2020). While the gut has previously been known to influence many aspects of the human body with these same pathways of communication, its influence on the brain had been ruled out due to the brain’s strong defensive wall of blood vessels, or the blood-brain barrier (BBB). The BBB protects the brain from many pathogens and molecules circulating in the blood, including those from the gut. Recently, researchers have discovered that while the BBB is highly selective, bacteria and microbiota from the gut can still pass through. This gives a basis for how unhealthy gut bacteria may causally influence behavior and other neuropsychiatric disorders. In fact, poor gut health has been linked to major depressive disorder, autism, and schizophrenia, with certain probiotics designed to help with gut health managing to also alleviate symptoms of these disorders. In one study, fecal samples from patients with schizophrenia were transferred into mice, resulting in mice presenting schizophrenic behaviors as well as having elevated levels of Glutamine and GABA in their hippocampus (Rutsch et al., 2020) compared to mice transplanted with healthy patient fecal matter. This one study provides excellent evidence as to how gut bacteria, those in schizophrenics, directly influenced the chemistry in the brain compared to a control.

    Moreover, in 2019, Kang et al. published the results of his 2 year-long study regarding whether microbial transfer therapy (MTT) could alleviate the symptoms of autism. In MTT, the subject’s bowel was cleansed followed by a fecal microbiota transplant (FMT) from a healthy donor. FMTs are designed to transfer healthy gut bacteria into an unhealthy gastrointestinal (GI) tract to aid in fostering the growth of healthy bacterial colonies. 2 years after the subjects received this treatment, subjects showed not only great improvement in GI function but also in symptoms of autism spectrum disorder (ASD). According to a professional evaluator based on the Childhood Autism Rating Scale (CARS), “At the beginning of the open-lab trial 83% of participants rated in the severe ASD diagnosis…At the two-year follow-up, only 17% were rated as severe…” (Kang et al., 2019). These results demonstrate how gut bacteria may play a causal role in psychiatric disorders previously thought to be completely isolated from the gut. This opens doors for new therapies for those struggling with these disorders.

    What’s more, gut bacteria have also been identified to play a causal role in sleep deprivation. In a recent study from 2022, Bowers et al. study the role of the gut-brain axis in sleep deprivation, using rats as an experimental model. In this study, rats were subjected to 5 days of little sleep, with one group fed a normal diet and the other group fed a GOS/PDX diet. The GOS/PDX diet is thought to support gut bacteria. In the recovery period that followed the 5 days of interrupted sleep, rats that were not being fed this diet ended up having an increase in REM sleep, state shifts, and NREM beta periods, which are all associated with sleep fragmentation and hyper-arousal (Bowers et al., 2022). Interestingly, rats that were fed this diet had longer and continuous bouts of sleep in this recovery period. Furthermore, after their fecal matter was investigated, rats fed the GOS/PDX diet were seen to have an increase in P. distasonis, a bacteria thought to aid the body during physiological stress and circadian rhythm dysfunction. This lends evidence as to how diets or even probiotics may lend much needed support to those struggling with sleep deprivation due to their influence on the brain.

    A collaborator on the previous research study, Martha H. Vitaterna, is currently working on investigating the gut microbiome in space, specifically looking at sleep-deprivation reports of astronauts and discerning if gut health could play a role in it. She is currently working with mice, modeling what it is like to be in space and monitoring changes in gut bacterial diversity in certain bacterial species that may impact sleep. Evidence resulting from this study could greatly aid astronauts who struggle to sleep, ultimately resulting in not only better states of health for these pioneers of research in space but also in a better understanding of gut health in general.

    
    With the many new promising directions regarding the GBA, researchers and patients alike can look forward to new novel therapies for neurological issues that range from schizophrenia to sleep loss. 

Bowers, Samuel J., Keith C. Summa, Robert S. Thompson, Antonio González, Fernando Vargas, Christopher Olker, Peng Jiang, et al. “A Prebiotic Diet Alters the Fecal Microbiome and Improves Sleep in Response to Sleep Disruption in Rats.” Frontiers in Neuroscience 16 (2022). https://www.frontiersin.org/articles/10.3389/fnins.2022.889211.

Kang, Dae-Wook, James B. Adams, Devon M. Coleman, Elena L. Pollard, Juan Maldonado, Sharon McDonough-Means, J. Gregory Caporaso, and Rosa Krajmalnik-Brown. “Long-Term Benefit of Microbiota Transfer Therapy on Autism Symptoms and Gut Microbiota.” Scientific Reports 9, no. 1 (April 9, 2019): 5821. https://doi.org/10.1038/s41598-019-42183-0.

Rutsch, Andrina, Johan B. Kantsjö, and Francesca Ronchi. “The Gut-Brain Axis: How Microbiota and Host Inflammasome Influence Brain Physiology and Pathology.” Frontiers in Immunology 11 (2020). https://www.frontiersin.org/articles/10.3389/fimmu.2020.604179.