Inside the small intestine: exploring the luminal microbiome with a novel swallowable device

Gut microbiome research has long relied on stool samples, leaving the small intestine— a central hub of digestion, metabolism, and immune activity—largely unexplored. The reason is simple: accessing this region of the human body is technically difficult.  That’s created a blind spot in our understanding of gut health. 

To address this challenge, scientists at Danone Research & Innovation (R&I) and Pelican Health went straight to the source. Fifteen healthy volunteers swallowed a novel, pH-dependent, gastro-resistant capsule called ‘HintSight’,  designed to minimally invasively collect luminal fluid from the small intestine safely. Then, using an integrated multi-omics strategy to analyze each sample, both the microbial composition and functional activity of the small intestine was revealed. 

“By sampling directly from the small intestine, we uncovered a microbiome that looks very different from what we usually see in stool!” notes Stephanie Cools Portier, Onebiome Laboratory Manager at Danone R&I.

For example, the small intestinal microbiome harboured fewer microbe species compared with the faecal microbiome, yet its composition varied much more from person to person.  

“Metabolomic profiling not only revealed a remarkable chemical landscape rich in bile and amino acids, reflecting the specialised physiology of the small intestine, but also enabled us to identify and isolate 90 bacterial species—including five potentially new taxa—revealing how much of this ecosystem remains to be explored,” adds Alexandre Tronel, Head of Clinical Applications at Pelican Health.  

“Yes, this is an exploratory study with a small sample size,” says Thomas Soranzo, CEO Pelican Health. “But what we’ve found in the small intestine is a vibrant, ever-changing ecosystem—something stool samples alone never revealed to us. So, to fully understand it, we need to start thinking about larger, multi-center studies.” 

By making what was previously inaccessible accessible, this research can reshape how the small intestine will be investigated. Future work exploiting the full potential of the HintSight capsule may include expanding cohort diversity and exploring clinical applications—from disease diagnostics to personalized nutrition and medicine, as well as microbiome-targeted therapies. 

“Using the latest HintSight capsule innovation to sample directly from the small intestine, we discovered a gut microbiome distinctly different from what stool samples have ever shown us.” says Stephanie-Cools, Onebiome Laboratory Manager.