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A Capsule to Look Inside an Irritable Bowel

The ingestible gas sensor

The ingestible gas sensor can give information about the most suitable diet and environmental conditions for each person. Eventually it will provide an image as to how medicine, diet and environment can affect the gut.

By Kourosh Kalantar-Zadeh

The impact of diet and illness on the gut can finally be revealed by swallowing an ingenious capsule that directly measures intestinal gases.

Our gut houses a large number of micro­organisms that colonise various part of the gut. The food we ingest activates these bacteria in different locations in the gut.

Complex carbohydrates fermented by these bacteria produce short chain fatty acids that we use as a source of energy. Some of the main by-products of this process are certain gases and vapours of volatile organic compounds.

The main fermentation gas is carbon dioxide. Hydrogen-producing bacteria in both the small and large intestines generate hydrogen (H2), while methanogens found mainly in the large intestine produce methane (CH4). Other gases produced include sulfur-containing compounds like hydrogen sulfide (H2S), which smells like rotten eggs, methanethiol, which smells like rotten fruit, and dimethyl sulfide, which smells like rotting cabbage, as well as nitrogen oxides (NOx) and diverse volatile organic compounds.

While we’re acutely aware that an abnormal increase in the production of intestinal gases causes bloating and flatulence, their impacts are more significant. Gases and volatile vapours of the gastrointestinal tract are directly associated with the state of health and can be used as biomarkers for medical diagnostics. For example:

  • an increase in H2 has been associated with bacterial overgrowth in the small intestine;
  • excessive CH4 in the colon may cause constipation-type irritable bowel syndrome and interfere with neurotransmitters in the gut; and
  • H2S can inhibit smooth muscle contractility of the gut, which also causes a different type of irritable bowel syndrome.

Considering that more than 15% of the Australian population suffers from the symptoms of irritable bowel syndrome at some stage in their lives, measuring these gases is of great importance.

In 2009 a medical academic approached me to develop an accurate breath analyser for hydrogen and methane measurements for low-cost, point-of-care diagnostics outside the clinical laboratory. These gases are generated in the gut, absorbed onto the gut walls and then recirculated to the lung via the blood stream before eventually being excreted by respiration. The most important conditions that this colleague wanted were reliability and repeatability of the measurements.

After some comprehensive investigations, I concluded that these conditions could not be met for any gas or vapour that is excreted from the mouth. There were too many interfering and random processes as gases can also be produced, stored and released by many organs in the human body at different intervals. I quickly concluded that to make sensible gas measurements they should be carried out near the sources of the gases inside the gut.

The first solution that came to my mind was to design indigestible capsules with incorporated gas sensors. I don’t think that it was a smart idea but it was certainly a practical solution. We have the most advanced laboratory in Australia for simulating all different mixtures of gases at RMIT. Consequently, testing the capsules could be a relatively easy task for my group

The next step was to engineer the electronics so that they could be reduced to fit into a capsule. One of my final year students, Nam Ha, took the smallest microprocessor on the market and placed it in sleep mode between measurements to increase the battery lifetime. Even then we could only use the smallest two to four small silver oxide button batteries.

The signals were coded so that many capsules could be used simultaneously with no interference from outside sources. The commercial 433 MHz band was used, and we designed the antennae to assure signal reception even at tens of metres distance from the capsules. We incorporated three gas sensors plus a temperature sensor.

The other challenge was to make a membrane for the cladding of the capsule, which needed to be almost transparent to gases of the gut but could also completely block the penetration of the gut liquor. My PhD student at the time, now Dr Kyle Berean, successfully achieved this task.

The science behind this happened to be fantastic, as we created membranes with nano-sized cavities that allowed the gas molecules to remain in the dissolution regime. This meant that they remained dissolved on membrane surfaces and released into the nano-cavities to gain fast kinetics and an extraordinary permeation rate from one side to another.

My colleague, Dr Jian Ou, also developed gas sensors that were selective to each target gas and could operate in both the aerobic environments of the stomach and first part of the small intestine, and the anaerobic environments in the distal small intestine and colon. We invented gas sensors based on physical absorption of gas molecules that negated the need for oxygen for their sensing. There are currently three sensors in the capsule and we hope to increase them to eight in the final design.

We finally fabricated the capsules, and changed the designs several times until we had the right sensors, membranes and associated electronic circuits, transmitter/receiver units, antennae and power supply for the human gas sensor capsule base. Nam also made a fantastic and user-friendly hand-held monitor and an app for smartphones.

The next step was testing the capsules. A National Health and Medical Research Council grant covered the cost this time. The development and presence of capsules were exciting enough to persuade gastroenterologist Prof Peter Gibson, nutritionist Dr Jane Muir and microbiologist Dr Chris McSweeney to join our team, while Prof Frank Dunshea’s group at The University of Melbourne supported us for the critical animal trials. These tests were invaluable as they allowed us to fine-tune the electronics and transmission systems.

After these tests we were able to design capsules that showed no gut retention (after adjusting the morphology and weight), were 100% reliable in gas measurements and their data transmission (after adjusting the output amplifiers, antennae and signal coding) and could also reach a lifetime that exceeded the time it takes for the capsule to leave the body.

We tested the pigs on low and high fibre diets, some medications, heat stress and in different conditions. We found that the diet and environmental effects on gases were beyond our imagination. The signals obtained from the gas sensors were very consistent with the diet and/or external conditions. For instance, the effect of heat on gas production was extraordinary, changing the gas ratios by orders of magnitude.

Accessibility to such large and reliable signals has significant consequences. For the first time, people will have access to a tool that presents the effect of diet on their body. This tool can also reveal some of the significant changes that occur inside the body even there is any apparent outside reaction.

Now we have a non-invasive tool that can be used for the diagnostics of gastrointestinal tract disorders. This tool can also reveal the effects of diet and environment on individuals.

All of these outcomes are significant. On average more than 20% of the world’s population will suffer from gut disorders at some stage of their live, but there is currently no reliable diagnostic tool for these illnesses. Our human gas capsule can give information about the most suitable diet and environmental conditions for each individual. Eventually it will provide an image as to how medicine, diet and environment can affect your gut and consequently your body.

We have received ethical clearance for human trials, and are now conducting crucial tests to delve into the exciting observations of gas profiles in humans. We will gain much more information from these experiments as humans can talk to us – unlike pigs!

We have already received a large number of enquiries from some significant companies. Many are keen to partner with us, which perhaps means that the human gas capsule will be one of the largest opportunities for Australian industry in years.

We hope that the human gas capsule goes to market sooner rather than later. This is a disruptive technology that will change the food and diagnostic industry as we know it, and also impact on the field of gastroenterology forever.

Kourosh Kalantar-Zadeh is Professor of Engineering at RMIT University.