Visceral Inflammation and Immune Activation Stress the Brain

Abstract

Stress refers to a dynamic process in which the homeostasis of an organism is challenged, the outcome depending on the type, severity, and duration of stressors involved, the stress responses triggered, and the stress resilience of the organism. Importantly, the relationship between stress and the immune system is bidirectional, as not only stressors have an impact on immune function, but alterations in immune function themselves can elicit stress responses. Such bidirectional interactions have been prominently identified to occur in the gastrointestinal tract in which there is a close cross-talk between the gut microbiota and the local immune system, governed by the permeability of the intestinal mucosa. External stressors disturb the homeostasis between microbiota and gut, these disturbances being signaled to the brain via multiple communication pathways constituting the gut–brain axis, ultimately eliciting stress responses and perturbations of brain function. In view of these relationships, the present article sets out to highlight some of the interactions between peripheral immune activation, especially in the visceral system, and brain function, behavior, and stress coping. These issues are exemplified by the way through which the intestinal microbiota as well as microbe-associated molecular patterns including lipopolysaccharide communicate with the immune system and brain, and the mechanisms whereby overt inflammation in the GI tract impacts on emotional-affective behavior, pain sensitivity, and stress coping. The interactions between the peripheral immune system and the brain take place along the gut–brain axis, the major communication pathways of which comprise microbial metabolites, gut hormones, immune mediators, and sensory neurons. Through these signaling systems, several transmitter and neuropeptide systems within the brain are altered under conditions of peripheral immune stress, enabling adaptive processes related to stress coping and resilience to take place. These aspects of the impact of immune stress on molecular and behavioral processes in the brain have a bearing on several disturbances of mental health and highlight novel opportunities of therapeutic intervention.

Anhedonia induced by high-fat diet in mice depends on gut microbiota and leptin

“…Several endogenous hormones are likely to contribute to the communication between the intestinal microbiota and the brain [43]. While the colonic expression of preproglucagon and PYY mRNA remained unaltered by HFD, the expression of both hormones was enhanced by antibiotic-induced microbiota depletion.…”

Excess Dietary Zinc Intake in Neonatal Mice Causes Oxidative Stress and Alters Intestinal Host–Microbe Interactions

“…Dysbiosis plays a main role in increasing intestinal permeability, which permits passage of bacteria‐derived products such as LPS into the portal circulation. In addition to IBD, dysbiosis, intestinal permeability and the ensuing inflammation, has been associated with numerous diseases including NEC, allergies, nonalcoholic fatty liver disease (NAFLD), cardiovascular disease, rheumatoid arthritis, and numerous neurological disorders such as bipolar, schizophrenia, autism, and Parkinson's . Systemic inflammation was assessed using an inflammatory cytokine protein array that detects 40 different inflammatory cytokines.…”

“…In addition to IBD, dysbiosis, intestinal permeability and the ensuing inflammation, has been associated with numerous diseases including NEC, [67] allergies, [68] nonalcoholic fatty liver disease (NAFLD), [69] cardiovascular disease, [70] rheumatoid arthritis, [71] and numerous neurological disorders such as bipolar, schizophrenia, autism, and Parkinson's. [72] Systemic inflammation was assessed using an inflammatory cytokine protein array that detects 40 different inflammatory cytokines. This approach was chosen to maximize the information we could obtain from the minimal amount of plasma obtained from 10-day-old mice.…”

Neuro-Immune Networks in Gastrointestinal Disorders

“…Several studies reported that a significant part of metabolites in mammalian blood are derived from the community of intestinal microbiota [55]. Via released molecules such as microbe-associated molecular patterns (MAMPs) and other microbial metabolites, microbiota communicate with other organs [56]. LPS, which belongs to the MAMP family, modulates distant organs via Toll-like receptor 4 (TLR4) action via different mechanisms [56].…”

“…Via released molecules such as microbe-associated molecular patterns (MAMPs) and other microbial metabolites, microbiota communicate with other organs [56]. LPS, which belongs to the MAMP family, modulates distant organs via Toll-like receptor 4 (TLR4) action via different mechanisms [56]. Noteworthily, TLR4 is expressed at several levels of the gut-brain axis such as in intestinal epithelial cells, enteric neurons, primary afferent neurons, and several cell populations in the brain (microglia, neurons, astrocytes) [57-60].…”