(183q) Dancing through Mucus: Unveiling Bacterial Motion in the Gut

Mucus, the gel-like matrix lining in the human gut, plays a pivotal role in health by regulating microbial interactions. While beneficial bacteria aid digestion and immunity, pathogens exploit mucins for colonization. Understanding bacterial motion within native mucus is crucial to unraveling disease mechanisms and developing targeted therapies. Recent work has demonstrated that bacteria exhibit modified swimming patterns in non-biological porous media due to being transiently trapped within pores [1]. This work investigates bacterial behavior in mucin gels, exploring whether these gels similarly transiently confine bacteria, bridging gaps in microbiome research and paving the way for innovative strategies to modulate gut health, e.g., through modification of bacterial motility.

Experiments were performed by examining E. coli motility in collected native porcine intestinal mucus. GFP-expressing E. coli were prepared via standard heat shock transformation. Bacteria were suspended in either mucus, maleate buffer, or “fed-state” media representing intestinal fluids and containing bile and lipids. Their motion was captured via fluorescence video microscopy and analyzed using multiple particle tracking algorithms. Our studies have revealed that in unconfined liquid environments such as maleate buffer, E. coli exhibit classic run-and-tumble motility. We tracked individual bacterial trajectories in two dimensions and computed mean squared displacement (MSD) as a function of lag time (τ). In maleate buffer, the MSD follows a power-law scaling of approximately τ^1.5 at short lag times, indicating extended superdiffusive behavior before transitioning to diffusive motion at longer timescales.

In contrast, when bacteria are suspended in native porcine intestinal mucus—a gel with a characteristic pore size of ~200 nm—their motion deviates significantly from unconfined behavior. In mucus, we observed shorter ballistic phases and earlier crossover to diffusive or even subdiffusive dynamics, with MSD scaling closer to τ¹ or below. This suggests that the physical confinement imposed by the mucus mesh transiently traps bacteria, reducing their motility and suppressing extended runs.

These results indicate that native mucus, like synthetic porous media, significantly alters bacterial transport by limiting run lengths and promoting confinement-induced subdiffusive behavior. The findings highlight that pore-scale structure in biological environments plays a key role in modulating microbial motion.

Future work will extend this study to gut-on-a-chip systems incorporating mucus-producing human intestinal epithelium, enabling more physiologically relevant modeling of host-microbe interactions. Key questions include whether bacterial motility actively remodels the mucus structure over time, how nutrient availability or the “fed state” modulates bacteria movement and interactions with the mucus matrix, and how these factors influence average trapping duration and run length. Such investigations will deepen our understanding of dynamic microbe-mucus interactions in the gut and inform strategies for manipulating microbial behavior in health and disease.

Reference:

1. Bhattacharjee, T., & Datta, S. S. (2019). Bacterial hopping and trapping in porous media. Nature Communications, 10(1). https:// doi.org/10.1038/ s41467-019-10115-1