Capsule-Sized Device Permits Noninvasive Exploration Of Small Intestine
By Deborah Borfitz
June 7, 2023 | An international team of researchers has completed preliminary testing of a swallowable device for collecting samples from people under standard, day-to-day conditions to better understand what is happening inside their small intestine. The lengthy organ has up to how been inaccessible unless individuals first fasted and were sedated, according to Professor Oliver Fiehn, Ph.D., director of the West Coast Metabolomics Center at the University of California, Davis.
This was the first of two phases of investigation for the novel CapScan device under a grant awarded by the National Institutes of Health (NIH) to inventor Dari Shalon, CEO of San Francisco Bay Area startup Envivo Bio. Initial testing proved the efficacy and safety of use of the high-tech capsule in 15 healthy subjects and allowed for design enhancements making it easier to recover from the stool, Fiehn reports.
Study findings appeared in a pair of articles that published recently in Nature (DOI: 10.1038/s41586-023-05989-7) and Nature Metabolism (DOI: 10.1038/s42255-023-00777-z). That gave the research team confidence that CapScan could reliably sample regions of interest along the upper intestinal tract, says Fiehn.
The study team took a multiomics approach to analyze the recovered samples for bacteria, viruses, host proteins, and metabolites from food to reveal differences—some “quite dramatic”—both person to person and in terms of what was found in the upper intestine versus the stool, he says. Associations between diet (including fruit and alcohol) and metabolites were also found.
Notably, for two participants who had taken antibiotics in the previous six months, investigators detected large variations in levels of bioactive fatty acid esters of hydroxy fatty acids (FAFHAs) and sulfonolipids, metabolites that are thought to be associated with preventing inflammation and diabetes. The bacterial species Blautia was most significantly associated with the discovery of these FAFHAs. “This shows that antibiotic treatments have long-lasting consequences, even in healthy people, disturbing metabolism over a long period of time,” Fiehn says.
Clear differences were seen in microbiota composition as well as chemical transformations, including the making of bioactive “signaling” lipids, he adds. The team also found a lot of new biomarkers for food consumption, which are difficult to detect in blood where the presence of markers reflects only recent intake.
The beauty of the CapScan approach is that it is sampling the upper intestine where 90% of human digestion happens, meaning locations where enzymes break down food and a multitude of metabolites are made, changed, and utilized. Most studies of gut metabolism and the gut microbiome are based on stool samples that reflect activity in the lower colon, says Jacob Folz, a former postdoctoral researcher in the Fiehn lab (now working for his second postdoc in a lab at the ETH Zurich, Switzerland).
The capsule takes samples along the entirety of the small intestine, approximately 20 feet in length, and into the beginning of the colon, says Fiehn. The esophagus and stomach are both easily sampled via endoscopy but have far fewer bacterial inhabitants.
With the current version of the device, people need to swallow four of the small capsules that each have a different thickness of a pH-sensitive coating, he explains. This determines when during the capsule’s journey through the digestion system that it opens to take a sample via a collection bladder that expands and draws in luminal contents through a one-way valve.
After each stop, CapScan is hermetically sealed, so no new microbes or other contaminants get inadvertently picked up, Fiehn continues. It is eventually defecated out and collected from the stool for metabolomic analysis.
It took a lot of optimization work over the years to get the device to reliably sample as intended, which was demonstrated in several different ways in the Nature Metabolism paper, says Folz.
One was by confirming that the pH of the sample being taken matched the known pH level of that section of the intestinal tract, and another was by linking the various chemicals and microbes in the collected sampled with their known locations in the small intestine.
Additionally, as shown in the Nature paper, researchers confirmed that the capsule collected samples from the right areas based on chemical modifications known to happen along the small intestine, adds Fiehn. Notably, bile acids are actively reabsorbed along the intestines and “the total amount is much lower in the distal small intestine compared to the proximal small intestine.”
Many more nutrients and energy and far fewer bacteria can be found in the duodenum at the beginning of the intestinal tract compared to the end, says Folz. To get a true read on the chemical and microbial environment therefore requires sampling at multiple locations. “Very different metabolism is occurring in different regions of the small intestine.”
An observational clinical trial is now starting that will enroll 15 patients of Silicon Valley Neurogastroenterology and Motility Center in Mountain View, California, who are in different stages of a malabsorption disorder known as small intestinal bacterial overgrowth (SIBO), one of the most frequent diseases of the small intestine, and another 15 healthy controls, Fiehn says. “We want to better understand the exact consequences [of SIBO] in terms of the bacterial populations found in these subjects and how metabolism is impaired.”
Investigators will do several intervals of testing over a three-year period. Among the study objectives is to learn more about the diversity of microbiomes associated with different malfunctions of food digestion in affected individuals, says Fiehn. If highly varied, individualized treatment would be warranted whereas if patterns emerge, one therapy may work for many if not most patients.
CapScan will be used by participants in their own at home, mimicking how the device would likely be deployed in a post-marketing setting, Fiehn adds. He likens this to over-the-counter finger stick blood tests popular with diabetic patients to assess their daily blood sugar levels, except the capsules would need to be mailed in for metabolomic analysis.
UC Davis is one of the leading academic institutions in the world for this sort of work, he notes. Folz was also part of the university’s food science and technology group for five years and has an abiding interest in food analysis and dietary biomarkers. Genomics experts from Stanford University and proteomics experts from Germany’s Max-Planck Institute also collaborated on device testing.
Moving forward, the newly discovered biomarkers for food consumption might well prove useful in confirming people are following specific diets, says Folz. Since these biomarkers can have physiological effects, researchers also have a chance to look at how different foods are digested and perhaps learn of some previously unknown chemical associations.
The NIH is currently funding large cohort studies across disease areas, including heart attack and Alzheimer’s, where researchers are asking participants what they eat to associate dietary patterns with health conditions and long-term outcomes, Fiehn says. But self-reporting is notoriously imprecise, so CapScan might be needed to end some of the ongoing debates such as whether red meat really increases the risk for cardiovascular health or eating fish can delay the onset of dementia.
The research team has “opened the door” to better understanding and alleviating digestion problems, which are surprisingly common, he adds. In the U.S. alone, up to 70 million people are affected by digestive diseases, according to the National Institute of Diabetes and Digestive and Kidney Diseases.