Intestinal bacterial biofilms modulate mucosal immune responses Original paper

What was reviewed?

This paper reviewed how intestinal bacterial biofilms shape mucosal immune responses and contribute to either immune homeostasis or chronic intestinal inflammation, with a strong focus on Crohn’s disease and related inflammatory conditions. The authors synthesized mechanistic evidence showing that biofilms are not passive bacterial aggregates but structured, metabolically active communities whose extracellular matrix components directly interact with host immune and epithelial cells. The review reframed biofilms as functional immune-modulating units within the mucus layer rather than as purely pathological structures. It emphasized that changes in bacterial lifestyle, particularly the transition from planktonic growth to biofilm formation, fundamentally alter how the immune system perceives and responds to resident microbes, thereby influencing disease susceptibility and persistence.

Who was reviewed?

The review integrated findings from human studies and experimental models. Human data included observations from healthy individuals and patients with Crohn’s disease, ulcerative colitis, and colorectal cancer, where mucus-associated biofilms were enriched and in closer contact with the epithelium. These clinical findings were supported by mechanistic studies in germ-free mice, antibiotic-treated mice, gnotobiotic models, and genetically susceptible hosts such as IL-10–deficient mice. Together, these systems allowed the authors to link specific biofilm components to immune activation, epithelial barrier disruption, and chronic inflammation.

What were the most important findings?

The review demonstrated that biofilm-associated bacteria, particularly members of the Enterobacteriaceae family, exert disproportionate effects on mucosal immunity compared with their planktonic counterparts. Major microbial associations included adherent-invasive Escherichia coli (AIEC), which expand in Crohn’s disease and form robust biofilms enriched in extracellular matrix components such as curli amyloid fibrils, cellulose, and type 1 pili. These biofilm components were shown to directly engage host pattern-recognition receptors. Curli fibrils activated TLR1/2 and the NLRP3 inflammasome, driving IL-1β, IL-6, IL-23, and downstream Th17 immune responses, as illustrated in the schematic on page 9. Type 1 pili interacted with epithelial CEACAM6 and TLR4, promoting bacterial adherence, increased epithelial permeability through claudin-2 induction, and heightened IFN-γ and TNF signaling.

Cellulose modulated immune responses indirectly by altering bacterial aggregation, iron availability, and exposure of other immunogenic surface molecules. Importantly, the review highlighted that biofilm components can be either protective or pathogenic depending on context. For example, oral exposure to curli promoted IL-10 production and reduced chemically induced colitis, whereas systemic exposure to curli–DNA complexes triggered type I interferon responses and autoimmunity. These findings underscored that biofilms reshape immune signaling not only through microbial composition but through physical structure and molecular presentation.

What are the greatest implications of this review?

For clinicians, this review clarifies that mucosal inflammation is driven not only by which microbes are present, but by how they organize, attach, and signal at the epithelial surface. Biofilm formation emerges as a critical determinant of immune activation in Crohn’s disease and other inflammatory disorders. Targeting biofilm-specific adhesion factors or matrix components offers a strategy to reduce pathogenic immune stimulation while preserving beneficial microbes, shifting therapeutic focus from eradication to spatial and functional control of the microbiome.