Neuroimmune Cross Talk in the Gut. Neuroendocrine and neuroimmune pathways contribute to the pathophysiology of irritable bowel syndrome

Abstract

Irritable bowel syndrome (IBS) is a common disorder characterized by recurrent abdominal pain, bloating, and disturbed bowel habit, symptoms that impact the quality of life of sufferers. The pathophysiological changes underlying this multifactorial condition are complex and include increased sensitivity to luminal and mucosal factors, resulting in altered colonic transit and visceral pain. Moreover, dysfunctional communication in the bidirectional signaling axis between the brain and the gut, which involves efferent and afferent branches of the peripheral nervous system, circulating endocrine hormones, and local paracrine and neurocrine factors, including immune and perhaps even microbial signaling molecules, has a role to play in this disorder. This minireview will examine recent advances in our understanding of the pathophysiology of IBS and assess how cross talk between hormones, immune, and microbe-derived factors and their neuromodulatory effects on peripheral nerves may underlie IBS symptomatology.

Keywords: GLP-1; interleukins; leptin; myenteric; submucosal.

Fig. 1.

IL-6R neutralization and antalarmin alter gastrointestinal dysfunction in WKY rats. A: histogram illustrating the number of fecal pellets excreted by Sprague-Dawley (SD, n = 7, 7, and 9) and Wistar-Kyoto (WKY, n = 10, 9, and 11) rats in the open field arena when administered saline, anti-interleukin (IL)-6 receptor antibodies (xIL-6R), or xIL-6R and antalarmin. B: histogram showing the pressure (mmHg) at which SD (n = 7, 7, and 9) and WKY (n = 10, 9, and 11) rats display pain behaviors in response to colorectal distension when treated with saline, xIL-6R, or xIL-6R and antalarmin. C: histogram illustrates the ratios of expression of occludin (n = 5) over the β-actin loading control (Con) in mucosal samples from the distal colon of SD and WKY rats treated with saline, xIL-6R, and xIL-6R with antalarmin (ant). *P < 0.05, **P < 0.01, and ***P < 0.001. Adapted from previously published work (6).

Fig. 2.

Brain-gut-microbiome signaling. The schematic illustrates potential signaling mechanisms between the luminal microbiota, the intrinsic and extrinsic colonic nerves, and the central nervous system with the role of neurocrine, endocrine, and immune factors indicated.