Biophysical determinants of biofilm formation in the gut

Abstract

The gastrointestinal (GI) tract harbors the most complex microbial ecosystem in the human body. The mucosal layer that covers the GI tract serves as a polymer-based defensive barrier that prevents the microbiome from reaching the epithelium and disseminating inside the body. Colonization of the mucus may result in the formation of structured polymicrobial communities or biofilms, a hallmark in pathologies such as colorectal cancer, inflammatory bowel disease, and chronic gut wounds. However, the mechanisms by which multispecies biofilms establish on the gut mucosa is unknown. Whether mucus-associated biofilms exist as part of a healthy mucosal barrier is still debated. Here, we discuss the impact that diet and microbial-derived polymers has on mucus structure and microcolony formation and highlight relevant biophysical forces that further shape nascent biofilms.

Figure 1.. Interactions of mucin with non-penetrating and infiltrating polymer solutions as a function of their molecular weight, concentration, flexibility, and charge.

(a) Non-penetrating high-molecular-weight (Mw) polymers osmotically compress the mucus layer. High-Mw polyelectrolytes achieve a higher compression due to mobilization of counterions. (b) Extracellular polymeric substances (EPS, in green) and proteins (red dots) generate osmotic forces that contribute to biofilm expansion. (c) Penetration of the mucus network by positively charged (polycationic), negatively charged (polyanionic), and neutral polymers and their effect on mucin’s relative viscosity as determined by changes in its hydrodynamic volume and as a function of mucin to polymer concentration. The dashed circles represent the changes in the mucin’s hydrodynamic volume.

Figure 2.. Biophysical forces influencing biofilm formation.

(a) Depletion and bridging aggregation of bacteria induced by mucin and bacterial exopolysaccharides. Polymer segments are illustrated as coils, whereas the depletion layer (left panel) is indicated by the dashed line around the aligned cells. Notice that in depletion aggregation, the polymer segments cannot approach the cell surface for a distance shorter than its radius of gyration. In bridging aggregation (right panel), polymer coils absorb to the cell surface, linking together neighboring cells via electrostatic interactions. (b) Compression forces that biofilms may experience when growing on and within the mucus layer. In uropathogenic Escherichia coli, compression forces upregulate EPS production. (c) Fluid flow-induced verticalization of bacteria favors the formation of 3D assemblies in vitro. (d) Catch bonds undergo dynamic force-induced extension and conformational changes in response to tensile force and are widespread among both pathogens and commensals. (e) Cell-to-cell interactions are critical during the formation of complex, highly structured polymicrobial biofilms such as those formed on teeth’s supra- and subgingival areas and may also contribute to the mechanics of in vivo biofilms.