Microbiota functional activity biosensors for characterizing nutrient metabolism in vivo

Darryl A. Wesener, Zachary W. Beller, Samantha L. Peters, Amir Rajabi, Gianluca Dimartino, Richard J. Giannone, Robert L. Hettich, Jeffrey I. Gordon

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Methods for measuring gut microbiota biochemical activities in vivo are needed to characterize its functional states in health and disease. To illustrate one approach, an arabinan-containing polysaccharide was isolated from pea fiber, its structure defined, and forward genetic and proteomic analyses used to compare its effects, versus unfractionated pea fiber and sugar beet arabinan, on a human gut bacterial strain consortium in gnotobiotic mice. We produced ‘Microbiota Functional Activity Biosensors’ (MFABs) consisting of glycans covalently linked to the surface of fluorescent paramagnetic microscopic glass beads. Three MFABs, each containing a unique glycan/fluorophore combination, were simultaneously orally gavaged into gnotobiotic mice, recovered from their intestines, and analyzed to directly quantify bacterial metabolism of structurally distinct arabinans in different human diet contexts. Colocalizing pea-fiber arabinan and another polysaccharide (glucomannan) on the bead surface enhanced in vivo degradation of glucomannan. MFABs represent a potentially versatile platform for developing new prebiotics and more nutritious foods.

Original languageEnglish
Article numbere64478
JournaleLife
Volume10
DOIs
StatePublished - Mar 2021

Funding

We are grateful to David O’Donnell, Maria Karlsson, Justin Serugo, Jiye Cheng, Jessica Forman, and Janaki Guruge for superb technical assistance during various phases of this study. We thank Artur Muszynski and Parastoo Azadi (University of Georgia) for linkage analysis of pea fiber and sugar beet arabinans (performed with support from the Chemical Sciences, Geosciences and Biosciences Division, Office of Basic Energy Sciences, U.S. Department of Energy grant [DE-SC0015662] to DOE-Center for Plant and Microbial Complex Carbohydrates at the Complex Carbohydrate Research Center), and Sanmathi Subbenaik (Nano Research and Environmental Laboratory at Washington University in St. Louis) for her help with zeta potential measurements. Michael Barratt and Michael Pat-node provided many helpful suggestions throughout the course of this work. These studies were supported by grants from the NIH (DK70977, DK078669) and Mondelez International. DAW is a Damon Runyon Fellow supported by the Damon Runyon Cancer Research Foundation (DRG–2303– 17). ZWB is supported by a National Institutes of Health grant (F30 DK123838). JIG is the recipient of a Thought Leader Award from Agilent Technologies. We are grateful to David O?Donnell, Maria Karlsson, Justin Serugo, Jiye Cheng, Jessica Forman, and Janaki Guruge for superb technical assistance during various phases of this study. We thank Artur Muszynski and Parastoo Azadi (University of Georgia) for linkage analysis of pea fiber and sugar beet arabinans (performed with support from the Chemical Sciences, Geosciences and Biosciences Division, Office of Basic Energy Sciences, U.S. Department of Energy grant [DE-SC0015662] to DOE-Center for Plant and Microbial Complex Carbohydrates at the Complex Carbohydrate Research Center), and Sanmathi Subbenaik (Nano Research and Environmental Laboratory at Washington University in St. Louis) for her help with zeta potential measurements. Michael Barratt and Michael Pat-node provided many helpful suggestions throughout the course of this work. These studies were supported by grants from the NIH (DK70977, DK078669) and Mondelez International. DAW is a Damon Runyon Fellow supported by the Damon Runyon Cancer Research Foundation (DRG?2303? 17). ZWB is supported by a National Institutes of Health grant (F30 DK123838). JIG is the recipient of a Thought Leader Award from Agilent Technologies.

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