Intestinal Barrier Function and the Brain-Gut Axis

Abstract

The luminal-mucosal interface of the intestinal tract is the first relevant location where microorganism-derived antigens and all other potentially immunogenic particles face the scrutiny of the powerful mammalian immune system. Upon regular functioning conditions, the intestinal barrier is able to effectively prevent most environmental and external antigens to interact openly with the numerous and versatile elements that compose the mucosal-associated immune system. This evolutionary super system is capable of processing an astonishing amount of antigens and non-immunogenic particles, approximately 100 tons in one individual lifetime, only considering food-derived components. Most important, to develop oral tolerance and proper active immune responses needed to prevent disease and inflammation, this giant immunogenic load has to be managed in a way that physiological inflammatory balance is constantly preserved. Adequate functioning of the intestinal barrier involves local and distant regulatory networks integrating the so-called brain-gut axis. Along this complex axis both brain and gut structures participate in the processing and execution of response signals to external and internal changes coming from the digestive tract, using multidirectional pathways to communicate. Dysfunction of brain-gut axis facilitates malfunctioning of the intestinal barrier, and vice versa, increasing the risk of uncontrolled immunological reactions that may trigger mucosal and brain low-grade inflammation, a putative first step to the initiation of more permanent gut disorders. In this chapter, we describe the structure, function and interactions of intestinal barrier, microbiota and brain-gut axis in both healthy and pathological conditions.

Microbiome Disturbances and Autism Spectrum Disorders

“…In this sense, it serves as the homeland security for the host to process and permit entry of essential extrinsic factors, while blocking transmission of detrimental microorganisms and antigens. This barrier processes over 100 tons in food-borne factors in an individual's lifetime (Alonso et al, 2014). Disruptions in this region are likely pivotal to gut-microbiota-brain comorbid disorders (Ait-Belgnaoui et al, 2012;Alonso et al, 2014).…”

“…This barrier processes over 100 tons in food-borne factors in an individual's lifetime (Alonso et al, 2014). Disruptions in this region are likely pivotal to gut-microbiota-brain comorbid disorders (Ait-Belgnaoui et al, 2012;Alonso et al, 2014). Leakiness of the barrier provides a portal for bacterial spread, along with increasing the potential for systemic transmission of antigens, virulence factors, other pathogens, and bacterial metabolites.…”

“…Leakiness of the barrier provides a portal for bacterial spread, along with increasing the potential for systemic transmission of antigens, virulence factors, other pathogens, and bacterial metabolites. Such factors may then impact brain function and inflammatory processes (Alonso et al, 2014). One study suggests that probiotic treatment with Lactobacillus farciminis restores the intestinal barrier and reduces the concentration of circulating LPS levels culminating in a blunting of the HPA response and neuroinflammation (Ait-Belgnaoui et al, 2012).…”

Role of Corticotropin-releasing Factor in Gastrointestinal Permeability

“…Numerous pathogens and toxins, hormones and neurotransmitters, and gastrointestinal and non-gastrointestinal diseases have been associated with an augmented intestinal permeability. 21 Among them, stress hormones and neurotransmitters have been consistently shown to modulate ion and water secretion, intestinal permeability, mucus secretion, and also intestinal flora.…”

Early-life enteric infections: relation between chronic systemic inflammation and poor cognition in children

“…[4][5][6] Prolonged or repeated enteric infections have long-lasting consequences, since the effects may extend throughout a lifetime and may even be multigenerational, leading to an unresolved vicious cycle of poverty, low education, and costly poor health and well-being of individuals and society. 7 Although chronic low-grade intestinal inflammation has been increasingly recognized as a factor contributing to poor intestinal absorption of nutrients, 8 the underlying mechanisms remain poorly understood. Recently, it has been shown that genetically engineered mice with toll-like receptor 5 deficiency only in enterocytes demonstrate low-grade inflammation and develop metabolic syndrome.…”