Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders

Abstract

The emerging links between our gut microbiome and the central nervous system (CNS) are regarded as a paradigm shift in neuroscience with possible implications for not only understanding the pathophysiology of stress-related psychiatric disorders, but also their treatment. Thus the gut microbiome and its influence on host barrier function is positioned to be a critical node within the brain-gut axis. Mounting preclinical evidence broadly suggests that the gut microbiota can modulate brain development, function and behavior by immune, endocrine and neural pathways of the brain-gut-microbiota axis. Detailed mechanistic insights explaining these specific interactions are currently underdeveloped. However, the concept that a “leaky gut” may facilitate communication between the microbiota and these key signaling pathways has gained traction. Deficits in intestinal permeability may underpin the chronic low-grade inflammation observed in disorders such as depression and the gut microbiome plays a critical role in regulating intestinal permeability. In this review we will discuss the possible role played by the gut microbiota in maintaining intestinal barrier function and the CNS consequences when it becomes disrupted. We will draw on both clinical and preclinical evidence to support this concept as well as the key features of the gut microbiota which are necessary for normal intestinal barrier function.

Microbes, Immunity, and Behavior: Psychoneuroimmunology Meets the Microbiome

“…These transmembrane proteins connect with the opposing plasma membrane, thereby forming a mechanical link between epithelial cells and establishing a barrier to paracellular. It has been shown that the structure of the intestinal barrier is formed by the end of the first trimester of pregnancy (Kelly et al, 2015). Epithelial cells with microvilli, goblet, and enteroendocrine cells appear by week 8 of gestation and tight junctions are detected from week 10.…”

“…The main function of the intestinal barrier is to regulate the absorption of nutrients, electrolytes, and water from the lumen into the circulation and to prevent the entry of pathogens and toxins (Kelly et al, 2015). Furthermore, regulation of the exchange of molecules between the environment and the host through the intestinal barrier influences the equilibrium between tolerance and immunity to self and non-self-antigens (Fasano, 2011).…”

Mechanisms of Stress-induced Visceral Pain

“…34 There is also evidence for alterations in microbiota balance in IBS and alterations in the bidirectional communication between the gut microbiota, the CNS, and the enteric nervous system. 35,36 …”

The human gut microbiome as source of innovation for health: Which physiological and therapeutic outcomes could we expect?

“…In the context of diseases of unknown etiology and with no available prevention or cure, man-microbe symbiosis was shown to be durably altered in conjunction with reciprocal aggravating signals. For instance, altered microbiota could promote intestinal hyperpermeability and inflammation, the latter promoting oxidative stress aggravating microbiota alteration [15][16][17]). …”