Technology enables sampling of an individual’s microbiome over time to observe changes associated with different illnesses or different diets
There is now a pill-sized device that can non-invasively collect and deliver a sample of gut bacteria taken directly from specific areas of a person’s gastrointestinal (GI) tract. One benefit of this new technology is that it can collect samples from the upper digestive system. Although not ready for clinical use, this is the kind of technology that would enable microbiologists and clinical laboratory scientists to add more microbiome assays to their test menu.
Researchers at Stanford University, Envivo Bio, and the University of California, Davis (UC Davis) have developed a vitamin capsule-sized device—dubbed CapScan—that can measure the microbial, viral, and bile acid profiles contained in the human intestines as it passes through on its way to being expelled.
Currently, scientists rely on stool samples to collect similar data as they are easy to gather and readily available. However, stool samples may not provide the most accurate analysis of the various microorganisms that reside in the human gut.
“Measuring gut metabolites in stool is like studying an elephant by examining its tail,” said Dari Shalon, PhD, Founder and CEO at Envivo Bio, one of the authors of the study, in a UC Davis news release. “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.” Shalon is the inventor of the CapScan device.
This demonstrates how technological advancements are giving scientists new diagnostic tools to guide selection of therapies and to monitor a patient’s progress.
The researchers published their findings in Nature titled, “Profiling the Human Intestinal Environment under Physiological Conditions.”
Microbiologists will take a special interest in this published study because, once confirmed by further studies, it would provide microbiology laboratories and clinical labs with a new way to collect samples. In clinical laboratories throughout the country, handling fecal specimens is considered an unpleasant task. Once cleared for clinical use, devices like CapScan would be welcomed because the actual specimen would be contained within the capsule, making it a cleaner, less smelly specimen to handle than conventional fecal samples.
“This capsule and reports are the first of their kind,” said Oliver Fiehn, PhD, Professor of Molecular and Cell Biology at UC Davis, in a news release. “All other studies on human gut microbiota focused on stool as a surrogate for colon metabolism. However, of course, the fact is that 90% of human digestion happens in the upper intestine, not the colon.” Clinical laboratories have long worked with stool samples to perform certain tests. If CapScan proves clinically viable, labs may soon have a new diagnostic tool. (Photo copyright: UC Davis.)
Collecting Small Intestine Microbiota
Human digestion occurs mostly in the small intestine where enzymes break down food particles so they can later be absorbed through the gut wall and processed in the body. Stool samples, however, only sample the lower colon and not the small intestine. This leaves out vital information about a patient.
“The small intestine has so far only been accessible in sedated people who have fasted, and that’s not very helpful,” Oliver Fiehn, PhD, Professor of Molecular and Cell Biology at UC Davis and one of the study authors, said in the news release.
According to their Nature paper, to perform their research the team recruited 15 healthy adults to participate in the study. Each participant swallowed four CapScan “pills,” either twice daily or on two consecutive days. The pills were designed to respond to different pH (potential of hydrogen) levels.
Each pill’s pH-sensitive outer coating enables scientists to select which area of the intestinal tract to sample. The outer coating dissolves at a certain point as it travels from the upper intestine to the colon. When this happens, a one-way valve gathers miniscule amounts of biofluids into a tiny, inflatable bladder. Once full, the bladder seals shut and the CapScan continues its journey until it is recovered in the stool. The researchers then genetically sequenced the RNA from the collected samples.
The scientists discovered that the microbiome varied substantially at distinctive sections of the GI tract. When compared to collected stool samples, the researchers determined that traditional stool sampling could not capture that variability.
“There’s enormous potential as you think about how the environment is changing as you go down the intestinal tract,” Kerwyn Huang, PhD, Professor of Bioengineering and of Microbiology and Immunology at Stanford, one of the authors of the study, told Drug Discovery News. “Identifying how something like diet or disease affects the variation in the individual microbiome may even provide the potential to start discovering these important health associations.”
The genetic sequencing also revealed which participants had taken antibiotics within one to five months before the study because their data was so incongruous with the other participants. Those individuals had distinctive differences in their microbiome and bile acid composition, which illustrates that antibiotics can potentially affect gut bacteria even months after being taken.
Researchers Use Multiple ‘Omics’ Approach
The researchers used “multiomics” to analyze the samples. They identified the presence of 2,000 metabolites and found associations between metabolites and diet.
According to the Envivo Bio website, the CapScan allows for the regional measurement of:
- Small intestine microbiota
- Secondary metabolites
- Drug metabolism
- Inflammatory biomarkers
- Bile acid transformations
- Fiber fermentations
“Overall, this device can help elucidate the roles of the gut microbiome and metabolome in human physiology and disease,” Fiehn said in the press release.
Future of Collecting Gut Bacteria
Using CapScan is a non-invasive procedure that makes it possible to sample an individual’s microbiome once, or to monitor it over time to observe changes associated with different illnesses or diets. Since it takes time for the device to pass through the digestive system, it is not a rapid test, but initial studies show it could be more accurate than traditional clinical laboratory testing.
“This technology makes it natural to think about sampling from many places and many times from one person, and it makes that straightforward and inexpensive,” Huang said.
Advancements in technology continue to provide microbiology and clinical laboratories with new, innovative tools for diagnosing and monitoring diseases, as well as guiding therapy selection by medical professionals. Though more research and clinical studies are needed before a device like the CapScan can be commonly used by medical professionals, it may someday provide a cutting-edge method for collecting microbiome samples.
—JP Schlingman
Related Information:
Profiling the Human Intestinal Environment under Physiological Conditions
Human Metabolome Variation along the Upper Intestinal Tract
Human Metabolome Variation along the Upper Intestinal Tract
Capsule Captures First Look Inside Digestion in Healthy People
A Vitamin-sized Device Samples the Gut Microbiome
Modern Multiomics: Why, How, and Where to Next?
Researchers Find Health of Human Microbiome Greatly Influenced by Foods We Eat