Editorial: the acid test – can bile acids predict recurrence of Clostridioides difficile infection?

Recurrent Clostridioides difficile infection (CDI) remains a significant burden; rates of first recurrence within 8 weeks of treatment are 15%– 25%.1 Prevention strategies include faecal microbiota transplant (FMT), suppressive vancomycin and bezlotoxumab. However, with universal access challenges to FMT, the high cost of bezlotuxumab and limited data confirming the efficacy of extended duration of suppressive vancomycin, these strategies are often reserved for second recurrences of CDI and beyond.2 It is, therefore, desirable to understand the mechanisms that predispose certain groups to recurrence and to optimise treatment options and surveillance of these individuals. One such mechanism may involve bile acids, but the relationship between CDI and bile acids is complex. In vitro, primary bile acids, including cholate, taurocholate and glycocholate, are important in the germination process of CDI spores, whereas chenodeoxycholate can inhibit the germination process. Secondary bile acids are thought to be protective against CDI; the success of antibiotics is thought to be underpinned by the promotion of secondary bile acids through microbial alterations.3,4 Furthermore, bile acids may play a significant role in the development of CDI. Specifically, in those with CDI, taurocholate as a potent germinant for CDI negatively correlated with microbialderived bile salt hydrolase (BSH) activity.5 In those who responded to FMT, BSH activity recovered, which correlated with a reduction in taurocholate concentrations. Mullish and colleagues have provided further mechanistic insights into the clinical significance of specific faecal bile acid profiles.6 The major strength of their study was that they characterised bile acid profiles in a welldescribed longitudinal set of stool samples that enabled comparison of bile acid profiles over time. The area under the curve comparisons further strengthened the importance of the recovery of secondary bile acids, deoxycholate and lithocholate, in inhibiting the activity of C. difficile. The identification of specific faecal bile acids and the predictive power of 5αcholanic acid−3,6dione on day one posttreatment is certainly promising, in enabling us to select a highrisk group that may benefit from preventive therapy. However, there remain further steps that will need to be taken before we achieve that goal. Transitioning towards narrowspectrum antibiotics may change the perturbations observed in intestinal microbiota, subsequently altering the faecal bile acid profile. Furthermore, the highly specialised nature of faecal bile acid analysis via liquid chromatographymass spectrometry will require significant investment before becoming commercially viable and widely available. Definitive correlation between the genomic signature and endproduct metabolites in stool microbiota will also further support and establish the pathogenic pathway for CDI, and further discovery of these changes in subsequent recurrences may further elucidate the pathogenesis of this disease. A significant step forward would be the integration of many of the other “omic” technologies, which may allow us to account for many of the confounders that may impact on the gut microbiome and develop this story further. Nonetheless, we applaud the authors for their work, and it certainly provides much promise in furthering our ability to tackle the complexities of recurrent CDI.