Letter: Gas‐Sensing Capsules Advance Colonic Physiology Research Toward Clinical Translation. Authors' Reply

We thank Drs. Koulaouzidis and Marlicz [1] for their interest in our interpretation of colonic gas signatures with the gas-sensing wireless motility capsule [2]. They raised important issues. Our interpretation that luminal concentrations of carbon dioxide (CO2) reflected overall microbial metabolic activity was questioned. CO2 is an end product of the majority of such activity—diffusion from the circulation is unlikely due to concentration gradients and CO2 consumption by microbes is likely to be quantitatively small [2]. However, the relevant sensor in the capsule cannot distinguish CO2 from methane (CH4), a product of CO2 (one molecule of CH4 generated from one molecule of CO2). The source of CO2 for this reaction surely is the same as for CO2 without methanogenesis. Furthermore, CH4 is detected at a similar molar concentration (i.e., 1% CO2 = 1% CH4). This is why we called it ‘CO2’, but it might be better called ‘CO2-equivalent’. The issue of how methanogenesis influences the hydrogen concentrations has been challenging to interpret because two hydrogen molecules are used for every CH4 molecule, suggesting that methanogenesis reduces hydrogen gas concentrations. Therefore, lower distal hydrogen concentrations relative to those in the proximal colon might reflect reduced availability of carbohydrate substrate and/or be the effect of distal methanogenesis. Supporting the latter is the belief that CH4 is mostly produced in the distal colon [3]. However, this assumption might not be correct [4]. If methanogenesis indeed occurs throughout the colon, reduced hydrogen concentrations may also occur throughout the colon and, therefore, would not impact the proximal–distal gradient. The value to clinical practice of quantifying proximal-distal hydrogen gradients is in providing physiological insight that might enable personalisation of fibre supplementation. We agree that precision in localising the capsule in the colon has some limitations; that is why most emphasis was on the two segments, proximal and distal, that can be determined more reliably. To better interpret the gradient, individuals should be characterised regarding methanogen status with multiple different complementary approaches in comparison to our capsule measurements to more clearly show the efficacy of our device. Strict dietary intervention studies are needed to show the gradient can be changed by delivery of more fermentable carbohydrate to the distal colon. We have demonstrated this in an interventional trial in patients with IBS [5]. While we did not assess their methanogen status, supplementation with a fermentable fibre—together with a non-fermentable fibre to drive delivery of the fermentable fibre to the distal colon—led to increases in distal hydrogen concentrations relative to those in the proximal colon. Hence, we have already moved toward ‘disentangling physiological variation from methodological noise’. Finally, the termination of marketing of the pH-sensing wireless motility capsule will have little impact on our capsule. The gas-sensing capsule is indeed more effective in identifying its location within the gastrointestinal tract [6, 7]. The pH-sensing wireless motility capsule provides little added insight into colonic physiology above that provided by the gas-sensing capsule [2]. Phoebe A. Thwaites: conceptualization, writing – original draft, writing – review and editing. Kourosh Kalantar-Zadeh: conceptualization, writing – review and editing. Peter R. Gibson: conceptualization, writing – review and editing. The authors' declarations of personal and financial interests are unchanged from those in the original article. This article is linked to Thwaites et al. papers. To view these articles, visit https://doi.org/10.1111/apt.70345 and https://doi.org/10.1111/apt.70396. The authors have nothing to report.