Host responses to mucosal biofilms in the lung and gut

Abstract

The impact of the human microbiome on health and disease is of utmost importance and has been studied intensively in recent years. Microbes promote immune system development and are essential to the production and absorption of nutrients for the host but are also implicated in disease pathogenesis. Particularly, bacterial biofilms have long been recognized as contributors to chronic infections and diseases in humans. However, our understanding of how the host responds to the presence of biofilms, specifically the immune response to biofilms, and how this contributes to disease pathogenesis is limited. This review aims to highlight what is known about biofilm formation and in vivo models available for the biofilm study. We critique the contribution of biofilms to human diseases, focusing on the lung diseases, cystic fibrosis and chronic obstructive pulmonary disease, and the gut diseases, inflammatory bowel disease and colorectal cancer.

Figure 1.. Characterization of Colonic Biofilms

Colon resections from a Malaysian CRC cohort were fixed in modified Carnoy’s (methacarn) and stained with oligonucleotide probes for Bacteroidetes (green), Lachnospiraceae (red), Fusobacteria (yellow), and Proteobacteria (magenta) as previously described (Drewes et al. 2017). Host nuclei are counterstained in DAPI. Images were captured at 40x by confocal microscopy. (A) A polymicrobial biofilm with Fusobacterial blooms from a tumor (left) and the paired normal biofilm without Fusobacteria (right). (B) A Proteobacteria-dominant biofilm from a tumor (left) and the paired normal biofilm (right). (C) Most CRC biofilms observed to date consist of scattered mixtures of bacteria (left), but complex 3D structures can be observed including microcolonies of specific species embedded within the larger biofilm (middle) or on necrotic tumor tissue (right). (D) In the outer mucus of tumors, distinct linear organization of the bacteria can sometimes be observed, potentially representing shear forces from the flow of gastrointestinal contents (left, center, and right images). Images in A and B were originally published in Drewes et al. 2017 NPJ Biofilms Microbiomes and have not been modified.