TY - JOUR

T1 - An Ingestible Self-Polymerizing System for Targeted Sampling of Gut Microbiota and Biomarkers

AU - Chen, Lu

AU - Gruzinskyte, Lina

AU - Jorgensen, Steffen Lynge

AU - Boisen, Anja

AU - Srivastava, Sarvesh Kumar

PY - 2020

Y1 - 2020

N2 - A proof-of-concept for the fabrication of a self-polymerizing system for sampling of gut microbiome in the upper gastrointestinal (GI) tract is presented. An orally ingestible microdevice is loaded with the selfpolymerizing reaction mixture to entrap gut microbiota and biomarkers. This polymerization reaction is activated in the aqueous environment, like fluids in the intestinal lumen, and causes site-specific microsampling in the gastrointestinal tract. The sampled microbiota and protein biomarkers can be isolated and analyzed via highthroughput multiomic analyses. The study utilizes a hollow microdevice (Su-8, ca. 230 mu m), loaded with an on-board reaction mixture (iron chloride, ascorbic acid, and poly(ethylene glycol) diacrylate monomers) for diacrylate polymerization in the gut of an animal model. An enteric-coated rat capsule was used to orally gavage these microdevices in a rat model, thereby, protecting the microdevices in the stomach (pH 2), but releasing them in the intestine (pH 6.6). Upon capsule disintegration, the microdevices were released in the presence of luminal fluids (in the small intestine region), where iron chloride reacts with ascorbic acid, to initiate poly(ethylene glycol) diacrylate polymerization via a free radical mechanism. Upon retrieval of the microdevices, gut microbiota was found to be entrapped in the polymerized hydrogel matrix, and genomic content was analyzed via 16s rRNA amplicon sequencing. Herein, the results show that the bacterial composition recovered from the microdevices closely resemble the bacterial composition of the gut microenvironment to which the microdevice is exposed. Further, histological assessment showed no signs of local tissue inflammation or toxicity. This study lays a strong foundation for the development of untethered, non-invasive microsampling technologies in the gut and advances our understanding of host-gut microbiome interactions, leading to a better understanding of their commensal behavior and associated GI disease progression in the near future.

AB - A proof-of-concept for the fabrication of a self-polymerizing system for sampling of gut microbiome in the upper gastrointestinal (GI) tract is presented. An orally ingestible microdevice is loaded with the selfpolymerizing reaction mixture to entrap gut microbiota and biomarkers. This polymerization reaction is activated in the aqueous environment, like fluids in the intestinal lumen, and causes site-specific microsampling in the gastrointestinal tract. The sampled microbiota and protein biomarkers can be isolated and analyzed via highthroughput multiomic analyses. The study utilizes a hollow microdevice (Su-8, ca. 230 mu m), loaded with an on-board reaction mixture (iron chloride, ascorbic acid, and poly(ethylene glycol) diacrylate monomers) for diacrylate polymerization in the gut of an animal model. An enteric-coated rat capsule was used to orally gavage these microdevices in a rat model, thereby, protecting the microdevices in the stomach (pH 2), but releasing them in the intestine (pH 6.6). Upon capsule disintegration, the microdevices were released in the presence of luminal fluids (in the small intestine region), where iron chloride reacts with ascorbic acid, to initiate poly(ethylene glycol) diacrylate polymerization via a free radical mechanism. Upon retrieval of the microdevices, gut microbiota was found to be entrapped in the polymerized hydrogel matrix, and genomic content was analyzed via 16s rRNA amplicon sequencing. Herein, the results show that the bacterial composition recovered from the microdevices closely resemble the bacterial composition of the gut microenvironment to which the microdevice is exposed. Further, histological assessment showed no signs of local tissue inflammation or toxicity. This study lays a strong foundation for the development of untethered, non-invasive microsampling technologies in the gut and advances our understanding of host-gut microbiome interactions, leading to a better understanding of their commensal behavior and associated GI disease progression in the near future.

KW - gastrointestinal tract

KW - radical polymerization

KW - gut microbiota

KW - 16s rRNA amplicon sequencing

KW - protein biomarkers

U2 - 10.1021/acsnano.0c05426

DO - 10.1021/acsnano.0c05426

M3 - Journal article

C2 - 32830478

VL - 14

SP - 12072

EP - 12081

JO - A C S Nano

JF - A C S Nano

SN - 1936-0851

IS - 9

ER -