Letter: Interpreting Faecal SCFA Enrichment in IBS‐D—Metabolic Signal or Transit‐Related Marker?

We read with great interest the study by Conley et al. [1], which identified a short-chain fatty acid (SCFA)-enriched faecal metabotype in patients with moderate-to-severe diarrhoea-predominant irritable bowel syndrome (IBS-D). The study is valuable because it moves beyond symptom-based classification and integrates faecal volatile organic compounds, metagenomic data, clinical symptom scores and whole-gut transit time. The finding that approximately one-third of patients exhibited an SCFA-enriched profile associated with abdominal pain, urgency, stool frequency and faster transit provides an important step towards biologically informed stratification of IBS-D. However, one issue that deserves further consideration is that faecal SCFA enrichment does not necessarily indicate increased microbial SCFA production. Faecal SCFA abundance is shaped by microbial fermentation, epithelial absorption, stool water content and intestinal transit [2]. Because the SCFA-enriched group also had faster whole-gut transit, higher faecal SCFA levels may partly reflect reduced absorptive opportunity or altered dilution rather than enhanced production. Future studies could strengthen this interpretation by incorporating absolute SCFA quantification, stool water correction, segmental transit assessment and host absorption markers such as epithelial SCFA transporter expression. Second, the SCFA-enriched metabotype may represent a rapid-transit diarrhoeal kinetic phenotype rather than an independent severe IBS-D subtype. Pain, urgency, loose stools, stool frequency and accelerated transit are closely interrelated in IBS-D [3]. Therefore, the observed association between SCFA enrichment and symptom severity may be partly mediated by transit dynamics [4]. Multivariable modelling, mediation analysis or structural equation modelling could help determine whether SCFA enrichment remains independently associated with pain or IBS severity after adjustment for whole-gut transit time, stool form and stool frequency. Third, the comparator group labelled as the ‘Other’ metabotype may not be biologically homogeneous. It included diverse metabolites such as ketones, aldehydes, terpenes, organosulphur compounds, indole and phenols, whereas the non-negative matrix factorisation analysis further suggested at least two non-SCFA signatures [5]. Combining these distinct metabolic states into one reference group may obscure clinically relevant heterogeneity and exaggerate the contrast with the SCFA-enriched group [6]. Future research may benefit from multidimensional metabolic phenotyping rather than a binary SCFA versus non-SCFA framework. In conclusion, this study provides an important foundation for metabolic stratification in IBS-D. Clarifying whether faecal SCFA enrichment reflects production, absorption, transit or their interaction will be essential before this metabotype can be translated into treatment selection or precision management. Longying Zhang: methodology, writing – original draft. Lifen Zhao: methodology, writing – review and editing, writing – original draft. Lina Liu: writing – review and editing, writing – original draft, conceptualization. The authors have nothing to report. The authors have nothing to report. The authors declare no conflicts of interest. This article is linked to Conley et al. paper. To view this article, visit https://doi.org/10.1111/apt.70677. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.