A Small Pill-Like Ingestible Microdevice for Site-Specific Microbiome Sampling in the Upper GI Tract

Area of Science:

• Gastroenterology
• Microbiology
• Biotechnology

Background:

• The gut microbiota composition varies significantly throughout the gastrointestinal (GI) tract.
• Accurate in vivo sampling from the upper GI tract is hindered by anatomical challenges and low genomic DNA yields.
• Understanding site-specific microbial communities is crucial for diagnosing and treating GI-related diseases.

Purpose of the Study:

• To develop and validate an ingestible microdevice for autonomous pyloric transit and in vivo sampling of the gut microbiome and protein biomarkers.
• To assess the safety and efficacy of the microdevice in Sprague-Dawley rats.
• To enable site-specific microbiota profiling and biomarker detection using advanced sequencing techniques.

Main Methods:

• An orally ingestible, pill-like microdevice (7 × 2.7 mm) with an enteric coating was designed for autonomous pyloric transit.
• The device features an inlet for luminal fluid, an activation chamber with a swelling hydrogel to prevent cross-contamination, and a sampling chamber.
• In vivo studies in rats (n=5) were conducted to evaluate device transit, safety (tissue injury, inflammation), genomic DNA yield, 16S rRNA sequencing, and protein biomarker detection (intestinal alkaline phosphatase).

Main Results:

• Successful autonomous pyloric transit was achieved in 4 out of 5 rats without adverse effects.
• The microdevice successfully retrieved sufficient genomic DNA (13.48 ± 4.66 ng) for 16S rRNA sequencing.
• Site-specific gut microbiota profiles distinct from fecal samples were identified, alongside the detection of intestinal alkaline phosphatase, confirming dual capability.
• Species-level microbiota identification was achieved using nanopore sequencing.

Conclusions:

• The developed ingestible microdevice represents a breakthrough platform technology for safe and effective longitudinal gut microbiome profiling.
• This technology overcomes previous sampling limitations, enabling detailed analysis of site-specific microbiota and biomarkers.
• The findings pave the way for advanced gut health diagnostics and research in larger animal models and human clinical studies.