The Microbiome-Gut-Brain Axis and Posttraumatic Stress Disorder

Robin Michelle Voigt ^1,2* Christopher A Lowry ³

• ¹ Rush University, Chicago, United States
• ² Rush University Medical Center, Chicago, Illinois, United States
• ³ University of Colorado Boulder, Boulder, Colorado, United States

One of the most promising areas of investigation into the role of the microbiome-gut-brain axis in responses to, and recovery from, trauma and stressors, is the role of short-chain fatty acids (SCFAs), which are metabolic byproducts of gut microbial fermentation. These compounds, including acetate, propionate, and butyrate, act as crucial signaling molecules, influencing neuroinflammation and brain function. Studies within this issue suggest that imbalances in SCFA production, particularly reduced propionate levels, may contribute to PTSD pathophysiology. This is supported by findings in Beyond specific metabolites, the research in this special topic underscores the importance of a holistic approach to PTSD treatment. Traditional therapies, while effective for some, often fail to address the intricate interplay between physiological and psychological factors. This special topic illuminates the need to consider the impact of chronic stress, neuroinflammation, and lifestyle factors on the microbiomegut-brain axis. "Using Lifestyle Interventions and the Gut Microbiota to Improve PTSD Symptoms" (Sugden & Merlo) advocates for lifestyle changes as a vital part of a holistic treatment approach. Lifestyle interventions, including dietary modifications and the use of prebiotics, emerge as potential adjunct therapies for current treatment approaches, offering a more comprehensive strategy for symptom management.Furthermore, the exploration of novel therapeutic targets extends beyond conventional probiotics and prebiotics. A preclinical study investigates the effects of Mycobacterium aurum and demonstrates the potential of mycobacteria to modulate the gut microbiome and mitigate the negative effects of chronic stress. This is demonstrated in "Effects of repeated intragastric administrations with heat-inactivated Mycobacterium aurum DSM 33539 on the stress-induced aggravation of dextran sulfate sodium (DSS) colitis in C57BL/6N mice" (Langgartner et al.), opening up exciting possibilities for the development of new psychobiotic interventions, harnessing the immunomodulatory properties of diverse microbial species.The use of advanced methodologies, such as Mendelian randomization, provides valuable insights into the causal relationships between gut microbiota, psychiatric disorders, and related comorbidities like irritable bowel syndrome (IBS). These studies reveal that genetic predispositions to PTSD and other psychiatric conditions can influence gut microbial composition and increase the risk of IBS, highlighting the shared pathophysiological pathways. This is shown in "Genetic Associations and Potential Mediators Between Psychiatric Disorders and Irritable Bowel Syndrome: A Mendelian Randomization Study with Mediation Analysis" (Zhang et al.).Finally, "The importance of the gut microbiome and its signals for a healthy nervous system and the multifaceted mechanisms of neuropsychiatric disorders" (Riehl et al.) provides a comprehensive overview of the communication between the gut microbiota and the brain, emphasizing the need for a multidisciplinary approach to understand and treat PTSD. By integrating research from microbiology, neuroscience, psychiatry, and genetics, we can unravel the complex interplay between the gut microbiome and the brain.In essence, this special topic illuminates the pivotal role of the microbiome-gut-brain axis in the pathophysiology and potential treatment of PTSD. From identifying distinct microbial signatures in persons with PTSD to exploring the therapeutic potential of SCFAs, prebiotics, and novel psychobiotics, the research presented here underscores the dynamic interplay between the gut and the brain. By integrating diverse methodologies, including systematic reviews, clinical trials, preclinical studies, and Mendelian randomization, we gain insights into the complex mechanisms underlying PTSD. Ultimately, this collection of studies advocates for a paradigm shift in PTSD management, emphasizing a holistic approach that considers the gut microbiome as a key player in mental health and paves the way for innovative, personalized interventions that may transform the lives of those suffering from the enduring effects of trauma.