Short-chain fatty acids in IBS: a potentially relevant stratification factor based on catabotyping analysis

Aim of the study: The gut microbiota is thought to be a crucial factor in the development of irritable bowel syndrome (IBS), and its metabolic byproducts, including short-chain fatty acids (SCFAs), are known to impact gut function and host health. However, the precise role of SCFAs in IBS remains a subject of debate. Methods: In this study, we analyzed the bacterial community structure by 16S rRNA gene profiling and measured SCFA levels by UPLC-MS/MS in fecal samples from healthy controls (HC; n=100) and non-constipated IBS patients (IBS-D and IBS-M; NC-IBS; n=240) recruited from several hospitals in Italy. Results and Conclusions: Our results indicate a significant difference between the fecal microbiomes of NC-IBS patients and HC subjects, with HC showing greater intra-sample biodiversity. Specifically, we observed a general expansion of Actinobacteria (particularly the species Collinsella aerofaciens) and a reduction of Bacteroidetes, butyrate, valerate, and succinate in the fecal microbiome of NC-IBS subjects. Furthermore, the implementation of a probability distribution distance metric enabled the classification of non-constipated IBS patients into two distinct subgroups based on their fecal SCFA levels (fecal catabotypes FC-L and FC-H) (see Figure 1), each characterized by unique bacterial signatures. Notably, we found that the FC-H and FC-L fecal catabotypes are associated with different IBS symptom severity, with a stronger direct relationship between fecal SCFAs and IBS symptoms observed in the FC-H catabotype. Our results suggest that the FC-H catabotype, with higher SCFA levels, may represent a distinct clinical phenotype of IBS that could have implications for diagnosis and treatment. This study provides a new perspective on the intricate relationship between the gut microbiome and bowel symptoms in IBS, highlighting the importance of personalized strategies for its management.