By Paul Nicolaus
January 14, 2020 | Despite the explosion of interest in the microbiome and the array of companies examining its composition, there remains an unmet clinical need for measuring microbiome function, says Mal Hebblewhite, CEO of Atmo Biosciences. And it’s a void his company is looking to fill.
In gastroenterological research and medicine, finding ways to reach the gut and gather insight remains a tricky task. Although it is possible to obtain a sample using a scope, that sample is prone to contamination and to an underestimation of the colony forming units, he explained. It is also tied to just one point in time and one location within the gut.
The human gastrointestinal tract is several meters long, and while it is possible to come in with a scope a certain distance, “you can’t get into the middle of it,” Hebblewhite told Diagnostics World News, “so it’s something of a mystery.”
Other than invasive tube insertion, the only way to measure key gases—which serve as indicators of gut health, disease, and disfunction—is through the use of breath tests. The main drawback, however, is the technique’s indirect nature. Gases produced within the gut are absorbed into the bloodstream, transferred into the lungs, and then exhaled through the mouth.
“So there really aren’t a lot of alternatives here when it comes to measuring these gaseous biomarkers,” he added. But Australian digital health company Atmo Biosciences is pursuing an approach that could help demystify gut physiology by measuring gases in real-time at the source of production, which “until now has been impossible.”
Decade-Long Development
The Atmo Gas Capsule, roughly the size of a multivitamin pill, is “a world-first ingestible gas-sensing capsule technology,” according to the company, which is capable of tracking location-specific gases within the human gut.
Breath testing involves the measurement of parts per million through the exhaled breath of hydrogen. “We are measuring percent concentration, or parts per hundred, so we’re thousands of times more accurate than a breath test,” Hebblewhite explained.
When swallowed, the capsule travels through the human body, Kourosh Kalantar-zadeh, a Professor of Chemical Engineering at the University of New South Wales told Diagnostics World News.
He and colleagues have developed the technology behind the capsule over the course of a decade—first at RMIT University and Alfred Health in Melbourne and now at the University of New South Wales in Sydney along with Atmo Biosciences.
Inside the polymer shell are gas sensors, a temperature sensor, a microcontroller, a radio-frequency transmitter, and batteries. The sensors are sealed within a semi-permeable membrane that blocks stomach acid and digestive juices while allowing gas to pass through.
The capsule measures various gasses and their concentrations every six minutes and transmits the information wirelessly to a small handheld receiver. From there, it connects to a mobile phone app, and the data is transmitted to the cloud for aggregation and analysis.
As envisioned, a medical doctor or clinical dietician would be able to look at that profile and recognize what is happening within the individual’s body, said Kalantar-zadeh, who is a scientific advisor for Atmo Biosciences.
The aim is to develop this technology into a safe, accurate, and convenient diagnostic tool for gastrointestinal conditions such as small intestinal bacterial overgrowth, irritable bowel syndrome, inflammatory bowel disease, and carbohydrate malabsorption and intolerance.
A 2018 pilot trial published in Alimentary Pharmacology and Therapeutics (doi: 10.1111/apt.14923) compared the performance of the gas-sensing technology against breath measurement testing. The findings, which relied on 12 participants, revealed that a prototype of the capsule measured over 3,000 times higher concentrations of hydrogen compared to breath tests.
Other research published in Nature Electronics (doi: 10.1038/s41928-017-0004-x) was conducted on seven healthy subjects. The results indicated that the capsule prototype could show the onset of food fermentation, which demonstrates the potential to monitor digestion and normal gut health.
The research team is now looking to bring their gut monitoring and diagnostic device to market. After forming Atmo Biosciences, the company announced a licensing deal with RMIT University to commercialize the capsule.
The next stage of development includes two human trials. The first is being conducted at Monash University and Alfred Hospital in Melbourne. The study will examine motility and transit time through the gastrointestinal tract for the capsule and compare it with existing standards for measuring transit time. The capsule is also being used in a second Monash study focused on irritable bowel syndrome patients.
Opening Up “Dark Pits”
The big problem in gastroenterological research and clinical medicine is that it’s difficult to access the small bowel and the large bowel without taking steps such as fasting or having a major laxation like a colonoscopy preparation, Peter Gibson, Professor of Gastroenterology at Monash University and Alfred Health told Diagnostics World News.
The use of breath tests to measure hydrogen production in the gut is problematic because it doesn’t reveal where within the gut the gas comes from, said Gibson, who is the lead medical advisor at Atmo Biosciences.
For clinical gastroenterologists, surgery and an endoscope used to be the only way to get into the deeper parts of the small bowel to take a closer look. The development of capsule endoscopy “completely changed the scene,” as it became possible for medical professionals to see the lining of the small bowel using a telemetry technique that sends data out and then converts it into images. That was the first development that opened up the so-called “dark pits,” he said.
Still, the microbiota—the bacteria and fungi and other microorganisms in the gut—are a crucial component of how the human body functions. While the Atmo capsule cannot measure what bacteria are present, it can show what they’re doing because it is the bacteria that produce the volatile organic compounds that can be measured.
In theory, it will open up the “dark pits” of the gut, he explained, as measurements reveal what is happening and where. “It gives us a window into what’s happening in the micromotor—what the bugs are doing in there,” Gibson explained. “It’s going to provide information that no one else has been able to get before in terms of gas profiling as well as transit time.”
To date, he said the gas-sensing capsule has shown “that it can measure at least hydrogen very well,” which is the gas the research team has focused on initially. The capsule also measures oxygen concentrations to track location and produces a profile along the gut. Essentially, it provides “an idea of how fast things empty through the stomach, how fast things go through the small bowel, and how long the colonic transit time is,” Gibson said.
It has traditionally been challenging to gather this type of insight in a cost-effective way that is also easy for the person involved. Other tools, such as a smart pill that measures pH, can be “quite expensive,” Gibson pointed out. Another option, like swallowing radioactive tracer, involves sitting under a camera every day for a week.
With Atmo’s capsule, on the other hand, “you just swallow it” and go about your day while wearing the receiver. The capsule has the potential to be useful in clinical practice, Gibson noted, as well as the potential to monitor dietary interventions.
Some are beginning to view the technology as a platform that can help test the benefits of their own products. Atmo Biosciences and microbial sciences company Seed Health recently announced a research collaboration, for example, that intends to use Atmo’s Gas Capsule in a series of clinical studies focused on their flagship probiotic.
The first study is expected to analyze the relationship between probiotics and antibiotics in the gut microbiome. “While antibiotics are a key frontline tool to treat and eliminate infections, they’re also known to negatively impact the diversity and function of the gut microbiome as reflected in the variety of side effects they cause,” Gregor Reid, Seed’s Chief Scientist, said in a news release.
“As a research and clinical tool, this device will contribute greatly to learning how interventions, including probiotics, alter the gut microbiome’s activity and metabolic readouts,” added Reid, who is a Distinguished Professor at Western University and Lawson Institute Chair of Human Microbiology and Probiotics in Canada.
Toward Commercialization
Although the capsule has initial research applications and is envisioned as a prescription product that would be made available through gastroenterologists, there may someday be consumer health applications as well. “You can imagine a consumer accessing their personalized data related to the gas profiles and using it to manage their gut health and looking at, for example, the effects of various foods and various diets,” Hebblewhite explained.
“We’re addressing this unmet clinical need to monitor and measure microbiome function, which will allow better diagnosis and management of personalized therapies for gastrointestinal disorders,” he added, and help lead to improved gut health and wellness.
A lot of the difficulties related to efforts undertaken by Atmo Biosciences ties into the notion that “this is going into the unknown,” Gibson pointed out. “The big challenge has been to show that what we say we’re measuring is what we’re measuring because there is no gold standard. You can’t say, ‘We have measured hydrogen concentration in this part, and it’s similar to what has been measured before,’ because no one has measured it before.”
The researchers intend to continue to work on validating the capsule as a marker that can accurately indicate transit times. This is crucial, Gibson said, because the numbers aren’t as meaningful if it is unclear whether the capsule is in the small bowel or the large bowel, for example. “We’ve got to do a lot of work to fully validate that,” he noted.
There are also plans, moving forward, to measure more than just hydrogen concentrations. The same technology can be used to measure short-chain fatty acids, for example, which play a role in immune system response and the regulation of the microbiome.
“All the technical issues can be overcome. To date they have been, one by one. It’s very reliable. It doesn’t block the bowel. It works really, really well,” Gibson said. “And what we need to do is have very, very careful validation of everything we do... so it really is a first-class product.”
Despite the desire to see this technology hit the market as soon as possible, “we’ve got a way to go yet,” Gibson acknowledged. The aim, according to Hebblewhite, is to make a regulatory submission for an initial indication in 2021, pending development and clinical trials.
Editor’s Note: For more on sensors for medical devices and ingestible and insertable sensors, see CHI’s Sensors Global Summit event, happening next in December 2020.
Paul Nicolaus is a freelance writer specializing in science, nature, and health. Learn more at www.nicolauswriting.com.