Hyaluronan: A Neuroimmune Modulator in the Microbiota-Gut Axis

Abstract

The commensal microbiota plays a fundamental role in maintaining host gut homeostasis by controlling several metabolic, neuronal and immune functions. Conversely, changes in the gut microenvironment may alter the saprophytic microbial community and function, hampering the positive relationship with the host. In this bidirectional interplay between the gut microbiota and the host, hyaluronan (HA), an unbranched glycosaminoglycan component of the extracellular matrix, has a multifaceted role. HA is fundamental for bacterial metabolism and influences bacterial adhesiveness to the mucosal layer and diffusion across the epithelial barrier. In the host, HA may be produced and distributed in different cellular components within the gut microenvironment, playing a role in the modulation of immune and neuronal responses. This review covers the more recent studies highlighting the relevance of HA as a putative modulator of the communication between luminal bacteria and the host gut neuro-immune axis both in health and disease conditions, such as inflammatory bowel disease and ischemia/reperfusion injury.

Keywords: enteric nervous system; gastrointestinal tract; gut microbiota; hyaluronan; immune system.

Figure 1

HA deposition in the rat colon myenteric plexus. (A–F) confocal image showing co-localization of HA with HuC/D (pan neuronal marker) in a median section of a colonic myenteric ganglion from control rats. HA was identified with a biotin-labeled HA-binding protein by streptavidin-FITC reaction. (A–C) Immunofluorescence was prevalently found in neuronal soma and in the perineuronal space. (D–F) HABP intensely stained the surface of the same ganglion and (A) interconnecting fibers (*). Bar 50 µm. (G–L) Confocal image showing co-localization of HA with HuC/D in a median section of a myenteric ganglion after DNBS-induced colitis in rats. (G–I) HABP fluorescence was prevalently found in the soma of myenteric neurons; perineuronal staining was absent. Several neurons displayed signs of distress with nuclear HuC/D translocation and faint cytoplasmic HuC/D immunoreactivity. Bar 100 µm. (J–L) HABP stained the surface of the same ganglion. Bar 50 µm (Adapted from Ref. [6]).

Figure 2

Schematic representation of HA-mediated effects on the gut microbiota and in the neuroimmune compartment in healthy and disease conditions. Abbreviations: HA: hyaluronan; PNN: perineuronal net.