Increasingly, research shows that the gut microbiome and metabolome play a critical role in numerous diseases as well as in food digestion, immune system regulation, and protection against pathogens, all of which have implications for human health and disease. Because the intestinal tract is regionally heterogenous, traditional sampling methods such as endoscopic biopsies and stool collection offer limited utility in understanding how intestinal gut microbes and metabolites impact human physiology.
In the Nature article, titled “Profiling the human intestinal environment under physiological conditions,” researchers from multiple universities and institutions describe CapScan’s capabilities to measure microbial, viral, proteomic, and bile acid profiles within the human intestines during normal digestion. The researchers report significant differences in microbiome composition, gene-class abundance, prophage induction, and the host proteome along various regions of the human intestine. Additionally, their findings detect and measure microbes and metabolites that are not present in stool or are inaccessible via endoscopic sampling.
“Our research confirms that, up until now, studies of the gut microbiome have really been studies of the stool microbiome, which missed out on most of the biological activity in our intestinal tract,” said Dari Shalon, Ph.D., founder and CEO of Envivo Bio. “By enabling researchers to sample and assess each of the diverse intestinal ecosystems separately and directly for the first time, CapScan opens the door to a new era of microbiome research.”
CapScan is a non-invasive, ingestible collection device that is about the size of a vitamin pill. Each device has a pH-targeted enteric coating, designed to dissolve at a pre-set rate based on the distinct pH levels of the various regions of the human intestines. Once this coating dissolves, CapScan’s internal bladder opens and draws in luminal content, which is then analyzed outside the body.
As detailed in the Nature paper, Shalon and collaborators from the Chan Zuckerberg Biohub, Max Planck Institute, Pennsylvania State University, Stanford University, University of California Davis, and two health care systems utilized CapScan to collect 240 intestinal samples from 15 healthy individuals. Each study participant ingested sets of four devices, which were all designed to open at progressively higher pH levels. Once the devices were evacuated, the scientists used multi-omics to analyze the massive sets of microbiome, metabolome, and proteome data collected regionally throughout the gastrointestinal tract.
“No one would expect to understand the headwaters of a river by sampling the river delta 1,000 miles downstream, yet this is how we’ve historically approached gut-related research,” said David A. Relman, M.D., Thomas C. and Joan M. Merigan professor of Medicine and professor of Microbiology & Immunology, Stanford School of Medicine, who co-led the study. “Our study demonstrates that there are differences between, as an example, bile acids in the small intestine versus stool samples that could be both scientifically and clinically meaningful.”
A companion study published in Nature Metabolism today describes additional spatiotemporal profiling of the gut metabolome using CapScan, including differences in dietary and lipid compounds. Taken together, the findings from both studies demonstrate the feasibility and utility of using CapScan to collect, characterize, and quantify the intestinal microbiota, metabolome, host proteins, and bile acids along the human intestine in a safe and routine manner.
“Our inability to see and measure the complex ecosystem of the gut has hindered our understanding of the features that make human intestines healthy or diseased, as well as our ability to develop new approaches to treat disease,” said Kerwyn Casey (KC) Huang, Ph.D., professor of Bioengineering and of Microbiology and Immunology, Stanford University, who co-led the study and is senior author on the Nature manuscript. “Our research suggests that we may be able to engineer new approaches to this problem.”
Envivo is also collaborating with researchers at Stanford Medicine on a clinical study using CapScan to understand the impact of the gut microbiome on the gut health of mothers and children in low- and middle-income countries with funding provided by the Bill & Melinda Gates Foundation.
“As we advance our CapScan technology with improved multi-regional sampling capabilities, we look forward to collaborating with biopharma companies and academic institutions to help improve our understanding of the highly complex gut microbiome and its role in health and disease,” added Dr. Shalon.
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