The Gut Microbiome and Mental Health: Implications for Anxiety- and Trauma-Related Disorders

Abstract

Biological psychiatry research has long focused on the brain in elucidating the neurobiological mechanisms of anxiety- and trauma-related disorders. This review challenges this assumption and suggests that the gut microbiome and its interactome also deserve attention to understand brain disorders and develop innovative treatments and diagnostics in the 21st century. The recent, in-depth characterization of the human microbiome spurred a paradigm shift in human health and disease. Animal models strongly suggest a role for the gut microbiome in anxiety- and trauma-related disorders. The microbiota-gut-brain (MGB) axis sits at the epicenter of this new approach to mental health. The microbiome plays an important role in the programming of the hypothalamic-pituitary-adrenal (HPA) axis early in life, and stress reactivity over the life span. In this review, we highlight emerging findings of microbiome research in psychiatric disorders, focusing on anxiety- and trauma-related disorders specifically, and discuss the gut microbiome as a potential therapeutic target. 16S rRNA sequencing has enabled researchers to investigate and compare microbial composition between individuals. The functional microbiome can be studied using methods involving metagenomics, metatranscriptomics, metaproteomics, and metabolomics, as discussed in the present review. Other factors that shape the gut microbiome should be considered to obtain a holistic view of the factors at play in the complex interactome linked to the MGB. In all, we underscore the importance of microbiome science, and gut microbiota in particular, as emerging critical players in mental illness and maintenance of mental health. This new frontier of biological psychiatry and postgenomic medicine should be embraced by the mental health community as it plays an ever-increasing transformative role in integrative and holistic health research in the next decade.

Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation

“…During the last decade, the human microbiome and the microbiota-gut-brain (MGB)-axis have become a novel epicenter in mental health and specifically stress-related research and have been already acknowledged as a potentially vital new determinant in the field of neuroimmunoregulation, brain development and behavior (219)(220)(221)(222)(223). The MGB-axis represents a bidirectional, key communication pathway between the immune system and the CNS, thus partly mediating the regulation of stress response and early life programming of the neuroimmune system (221,224).…”

“…Stress-related disruption of the dynamic host-microbe interaction at these critical periods can lead to alterations of the bacterial colonization of the gut in early life and vice versa (242,243). As the microbiome plays an important role in the programming of the HPA axis and stress reactivity (244), ELS/CT may affect the signaling of the MGB axis in a major fashion and alter not only immune, but also CNS and stress system functioning with lifelong emotional and behavioral consequences (i.e., higher risk of neurodevelopmental disorders) (223,239,241,245,246).…”

Global research trends in microbiome-gut-brain axis during 2009–2018: a bibliometric and visualized study

“…Functional imaging, functional magnetic resonance imaging and magneto encephalography, have enabled us to identify real time changes in neurological activity and correlate these with changes in behavior or perception [12][13][14]. Advances in computational biology are beginning to explain how these multifaceted and complex systems interact with each other [15,16].…”

Outer membrane vesicles enhance tau phosphorylation and contribute to cognitive impairment

“…Recent research techniques and results focused on the interaction of the gut microbiota (GM) with the central nervous system ("microbe-gut-brain axis") (Kowalski & Mulak, 2019;Roubalova et al, 2019), and AD has been associated with an abnormal GM composition (Bostanciklioğlu, 2019;Doulberis et al, 2019). GM affects the nervous system including vagal nerve and adrenergic nerve activation, as well as the production of neurotransmitters or by evoking the enteroendocrine cells, enterochromaffin cells and the mucosal immune system to relay gut-brain signalling (Collins, Surette, & Bercik, 2012;Li et al, 2018); GM also regulates the release of cortisol to govern the activation state of brain microglia and effect cytokine release, as well as influence the levels of pro-inflammatory cytokines and anti-inflammatory cytokines in the blood to affect the central nervous system (Malan-Muller et al, 2018;Osadchiy, Martin, & Mayer, 2019). However, the specific substances, mechanisms and signalling pathways acting on the brain still need to be further explored.…”