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Three-dimensional Quantification of Intestinal Mucus Using Whole-mount Tissue Imaging

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Quantifying and Engineering Mucus Adhesion of Probiotics.

Zachary J S Mays¹, Todd C Chappell¹, Nikhil U Nair¹

¹Department of Chemical and Biological Engineering , Tufts University , Medford , Massachusetts 02155 , United States.

ACS Synthetic Biology

|January 8, 2020

Summary

Scientists developed a new assay to measure how well probiotics stick to gut mucus. This helps control engineered microbes for better drug delivery and therapeutic effects.

Keywords:

cell adhesion lactic acid bacteria microbiome mucoadhesion mucus probiotics

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Area of Science:

Microbiology
Biotechnology
Gastroenterology

Background:

Gastrointestinal (GI) mucus is crucial for host-microbiota interactions, offering protection and a habitat for gut microbes.
Engineered microbes represent a promising frontier in therapeutics, but controlling their adhesion is key for efficacy.

Purpose of the Study:

To develop and validate a novel in vitro assay for quantifying mucus adhesion of probiotic bacteria.
To enable precise control over the mucoadhesive properties of microbial therapeutics.

Main Methods:

An in vitro plate-based assay was designed, immobilizing mucus to the plate surface to isolate cell-mucus interactions.
Probiotic adhesion was measured across a range of cell concentrations to derive dose-dependent binding parameters.
Heterologous expression and modification of surface proteins in *Lactococcus lactis* and *Escherichia coli* were used to modulate mucoadhesion.

Main Results:

The assay provides quantitative metrics for mucus-binding capacity, avidity, and cooperativity for different probiotic strains.
Specific surface proteins and cell components influencing mucoadhesion were identified and manipulated.
The study demonstrated the ability to engineer microbial mucoadhesion through targeted genetic modification.

Conclusions:

The developed assay is a valuable tool for characterizing and engineering the mucoadhesive properties of probiotics.
Controlling microbial mucoadhesion is essential for optimizing the delivery and therapeutic outcomes of living therapeutics.
This work lays the foundation for designing more effective engineered microbial therapies for gastrointestinal conditions.