Letter: Gas‐Sensing Capsules Advance Colonic Physiology Research Toward Clinical Translation

We commend Thwaites et al. [1] for their innovative application of tandem pH- and gas-sensing capsules to explore colonic fermentation in ambulant healthy individuals. Their observation of consistent proximal-to-distal rises in luminal pH (6.3–7.0, p < 0.001) and carbon dioxide (CO2) (12.7%–18.8%·h/h, p < 0.001; rs = 0.76), alongside variable hydrogen (H2) gradients (69% increase, p = 0.02), highlights the potential of these technologies to reveal in vivo metabolic patterns that have historically been inaccessible. Nonetheless, a few points merit consideration. The capsule's thermal conductivity sensor detects CO2 and methane (CH4) indistinguishably at a 1:1 M ratio. CH4 is produced in up to 30% of healthy adults [2] and predominantly in the distal colon [3], with volumes approaching 2 L/day [3]. Consequently, reported “CO2” concentrations may partly reflect methanogenesis. This distinction is not trivial since CH4 not only consumes H2 but also modulates motility; its presence probably explains why 31% of participants showed falling H2 concentrations distally. Without concurrent breath CH4 testing [4], the interpretation of CO2 as a direct marker of “overall microbial activity” may be problematic. Furthermore, participants followed their habitual diets, estimated to vary in fibre intake between 10 and 30 g/day [5]. Such variability strongly influences fermentable substrate availability and may account for the wide interquartile range in distal H2 (0.9%–4.8% h/h). Fibre supplementation trials have demonstrated that diet shifts proximal–distal H2 gradients [6]. In the absence of dietary records or microbiome profiling, it is difficult to disentangle physiological variation from methodological noise. The paper's supplementary data reveal up to 20% data loss in some quartiles. While time-normalised area under the curve (AUC) analysis mitigates bias, this may underestimate variance in patients with slow or disordered transit. Moreover, dividing the colon into transit quartiles is pragmatic but assumes linear capsule progression, despite known retrograde movement in around 20% of cases [7]. While a combining capsules approach is commendable [8], the global discontinuation of SmartPill was announced in June 2023, with stocks depleted by September 2023. This underscores the need for integration with localisation technologies, such as electromagnetic tracking [9], to improve spatial accuracy. The authors are right to highlight the potential of capsule-based technology to personalise fibre therapy [10], a long-standing but empirical intervention in gastroenterology. However, until CH4 can be distinguished from CO2, and/or until capsule-derived gas signatures are validated against dietary intake, microbial composition, and short-chain fatty acid delivery, translation into clinical practice should be cautious. In conclusion, telemetric capsules represent a major step forward in mapping human colonic physiology. This study demonstrates feasibility and reproducibility, but methodological refinements, particularly CH4-specific sensing [10], dietary and microbiome integration, and validation against established biomarkers, will be required before the full clinical potential can be realised. Anastasios Koulaouzidis: conceptualization, writing – original draft, writing – review and editing, project administration. Wojciech Marlicz: validation, writing – review and editing, formal analysis. Artificial intelligence tools (ChatGPT5, OpenAI, San Francisco, CA, USA) were used solely to assist with language editing and style refinement during manuscript preparation. No AI-generated data or figures were included. All scientific content, interpretations, and conclusions were developed, verified, and approved entirely by the authors. A.K. received research support in the form of grants from Given Imaging Ltd under the auspices of the European Society of Gastrointestinal Endoscopy (ESGE), and from IntroMedic (also noted as SynMed/Intromedic), and has served as a consultant for Jinshan Ltd, with consultancy fees from Jinshan and lecture honoraria from Covidien/Medtronic. He has also been co-founder and director of iCERV Ltd. Additionally, he has benefited from lecture honoraria and educational travel support from a range of entities including Jinshan, Dr Falk Pharma UK, Ferring, Aquilant, and Almirall, and has participated in advisory board activities for companies such as Tillots, Ankon, and Dr Falk Pharma UK. W.M. is a shareholder and co-founder of Sanprobi sp. z o.o. and Endoklinika sp. z o.o. A.K. is a co-founder, shareholder of AJM Med-i-caps Ltd. and consultant for Jinshan Science & Technology Ltd. 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.70412. The authors have nothing to report.