Fantastic Voyage is a 1966 American science fiction film, starring Stephen Boyd, Raquel Welch and Donald Pleasance as the crew of the submarine/spaceship, Proteus, that is able to shrink to microscopic size to travel into the body of an injured scientist to remove a clot on his brain. Isaac Asimov was commissioned to write the novel about the idea.
Truth is sometimes stranger than fiction. In the nineteen eighties, smart pills were developed to record pressures and pH in the gut and transmit the signals wirelessly to monitors outside the body. By 2000, similar pills were equipped with cameras and able to transmit images of the parts of the small intestine that other endoscopes couldn’t reach. Now a paper has been published demonstrating the ability of a smart pill, no bigger than a fish oil capsule, to detect concentrations of gases in the gut. Within the intestine, hydrogen exists in concentrations at least 5 orders of magnitude above that recorded in the breath, where it has been diluted by passage through the body and by the air in the lungs. Direct measurement by a capsule therefore provides a much more sensitive index of hydrogen production in the gut.
The capsule, pioneered by a team from the RMIT University, Melbourne working in association with the Department of Nutrition and Gastroenterology at Monash University, uses a combination of thermal conductivity and semiconducting sensors, controlled by adjusting their heating elements, to detect concentrations of oxygen, hydrogen and carbon dioxide as it travels the length of the gut. By this means, gas profiles of human volunteers have been obtained while they digested diets containing different amounts of dietary fibre. It has to be said that the data from this study are not easy to interpret, partly because the initial subject was constipated and in pain and showed evidence of gastric stasis and hydrogen production.
Like space probes, the clinical interpretation of data from smart pills relies on an accurate knowledge of where the capsule is situated. The authors state that this can be achieved by measurement of ‘oxygen equivalent’ concentration, which is around 65% in the stomach because of the presence of oxidising agents, falls to around 25% in the jejunum, 5% in the ileum and less than 1% in the anaerobic environment of the colon. They claim to have confirmed the location by concomitant ultrasound imaging – though it can be very difficult to interpret ultrasound images of loops and coils of intestine. Oxygen equivalent is not a direct measure of gaseous oxygen; it is more an indicator of oxygenation. Results in the first subject showed that the high fibre diet increased colonic oxygenation to around 20%, raising questions about the validity of the oxygen sensor to provide an accurate index of location under all circumstances.
Nevertheless a further study in four healthy volunteers clearly showed an increase in hydrogen as the capsule entered the colon, though ingestion of a high fibre diet delayed transit through the small bowel, but accelerated transit through the colon while a lower fibre diet accelerated small bowel transit and delayed colonic transit. More controlled studies of the effect of diet will need to be carried out together with other methods to measure transit and gas production in order to interpret these preliminary data.
Not only can this capsule monitor the effects of diet on gas production but it may be used as a diagnostic tool. Small Intestinal Bacterial Overgrowth remains a controversial diagnosis, which is based on the basis of ‘abnormal’ breath hydrogen profiles following a drink of lactulose or glucose. The demonstration of high hydrogen concentrations in the small intestine would confirm the diagnosis and end the controversy. I also wonder whether modifications to this capsule might allow measurement of methane, a toxic gas which has been associated with constipation.
The capsule is two and half centimetres long and a centimetre wide. Indigestible material of this size would not be emptied with a meal but would be evacuated by the strong propagated gastric contractions that develop several hours later when the stomach is otherwise empty. And lower down in the colon, such a large bolus might need to await the development of a high amplitude propagating contraction or mass movement. Neither scenario would be indicative of the passage of food or food residues. Thus, the results would more reflect the way this particular spaceship affects the function of the gut than the effects of meals or diet. Studies conducted in my laboratory many years ago showed that indigestible plastic pellets increased stool mass and accelerated transit through the gut, while the presence of a plastic tube in the gut delayed gastric emptying and accelerated transit through the small intestine and the colon. The results of any research study are always affected by the means used to measure them.
Finally, it is likely that gassy symptoms are produced by the quantity of gas produced and not by its concentration. Measuring concentrations of gas could be misleading. A high fibre diet that has a low residence in the colon might increase gas elimination as flatus, lowering its concentration, while a low fibre diet might cause stasis, lower gas production but cause a build up of concentration.
In conclusion, the development of this device is undoubtedly a great technical achievement, but the clinical and scientific interpretation and applications would need extensive validation studies before it becomes available for use in the clinic.
The good ship, Proteus, only had 24 hours to complete its task and escape from the body before it expanded to full size. Lets hope the patient took a high fibre diet.