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Edible Capsule Maps the Hidden Microbiome in Our Upper Intestine

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New research has utilized a custom capsule to study a previously hard-to-reach area of the gut, potentially opening up a whole new area of study into the chemicals and microorganisms that live there. Two new papers, published in Nature and Nature Metabolism, document the pill’s power.

The world inside our bodies

Advances in genomics and other fields like metabolomics – which examines the metabolites our bodies release and use to power themselves – have enabled us to interrogate our digestive systems to an unprecedented level of detail in the last decade.

One of the central tools in this field has been the analysis of stool samples to dissect the unique chemical and microbiological cocktail present. These findings have been used as a proxy for the actual metabolome present inside our bodies, but the researchers behind the new study – a collaboration that includes scientists from the University of California, Davis (UC Davis), Stanford University and Envivo Bio Inc. – say that this technique provides an incomplete picture.

“Measuring gut metabolites in stool is like studying an elephant by examining its tail,” said Dari Shalon of Envivo Bio, inventor of the CapScan device and co-author on the papers. “Most metabolites are made, transformed and utilized higher up in the intestines and don’t even make it into the stool. CapScan gives us a fuller picture of the gut metabolome and its interactions with the gut microbiome for the first time.”

CapScan can provide a view of metabolites in the small intestine – where the majority of enzyme-mediated digestion happens in our bodies. “The small intestine has so far only been accessible in sedated people who have fasted, and that’s not very helpful,” said Professor Oliver Fiehn, director of the West Coast Metabolomics Center at UC Davis and senior author of the Nature Metabolism paper. Stool samples mainly provide a picture of the lower colon rather than the small intestine.

Custom sampling

The new capsule, once swallowed, travels through the digestive system, sampling fluid and microorganisms as it passes through. It can then be recovered from stool. Areas of the digestive system have different levels of pH. By using sensors on the capsule, the researchers can choose which region to sample from.


In the Nature paper, 240 intestinal samples from 15 people were collected, providing a deep dive into the digestive process. Their multiomics-based experimental design allowed them to capture many different measurements, including genomic and metabolic information. Viruses, proteins produced by the body, bacteria and metabolites were all captured by the analysis, showing that all of these differ between the upper intestine and the stool samples normally analyzed.

Nearly 2,000 metabolites were identified, and associations were noted between diet – such as the amount of alcohol or fruit consumed – and the metabolome. The Nature Metabolism paper looked at this variation in detail, showing that two participants in the study who had been prescribed antibiotics in the last six months had different levels of metabolites that may offer protection against inflammation and diabetes. “Overall, this device can help elucidate the roles of the gut microbiome and metabolome in human physiology and disease,” Fiehn concluded.


Shalon D, Culver RN, Grembi JA, et al. Profiling the human intestinal environment under physiological conditions. Nature. 2023:1-11. doi:10.1038/s41586-023-05989-7

Folz J, Culver RN, Morales JM, et al. Human metabolome
variation along the upper intestinal tract. Nat. Metab. 2023:1-12. doi:

This article is a rework of a press release issued by UC Davis. Material has been edited for length and content

Meet the Author
Ruairi J Mackenzie
Ruairi J Mackenzie
Senior Science Writer