Gut microbiome and plasma lipidome analysis reveals a specific impact of Clostridioides difficile infection on intestinal bacterial communities and sterol metabolism

Abstract

Abstract Background Gut microbiome studies are helping to understand the mechanisms by which Clostridium difficile infection (CDI) and its recurrences are favoured, as well as recovery from it through different types of treatment. In addition to the impact on microbiome composition and given the metabolic changes occurring at the gut level during CDI, our interest focused on the effects at the local and systemic levels, both during the infection and its treatment, by paying particular attention to bile acid (BA) and cholesterol metabolism due to their close relationship to CDI pathogenesis. A cross-sectional case-control study was performed by obtaining stool and plasma samples from healthy volunteers and patients with CDI diagnosis, primary or recurrent, before and after treatment (antibiotic or faecal material transfer (FMT)) for further analysis. Faecal total DNA was used for sequencing the V3 and V4 variable regions of the 16S rRNA gene. Plasma BAs and lipid profile were established using liquid chromatography-tandem mass spectrometry. Results Specific alterations were observed in the gut microbiota of CDI patients, especially in RCDI, characterized by a loss of microbial richness and diversity and related to a reduction in short-chain acid-producing bacteria and increase in bile salt hydrolase-producing bacteria. FMT-treated patients showed a better restoration of the microbiota than antibiotic-treated patients, resembling that of healthy controls and displaying increased levels of Eubacterium coprostanoligenes, a coprostanol-reducing bacterium. Furthermore, CDI and treated patients exhibited a significant rise in total plasma BA content, particularly in taurine-conjugated BAs. Plasma lipidome analysis revealed a global decline in circulating lipids in CDI patients, with the largest impact on cholesteryl esters. We also identified in CDI patients a specific and consistent decrease in the levels of lipid species containing linoleic acid – an essential fatty acid – which recovered after treatment. Conclusions Analysis of the plasma lipidome reflects the impact of CDI on the gut microbiota and its metabolism, evidencing changes in cholesterol, fatty acid, and BA metabolism that are possibly related to the specific alterations observed in gut microbial communities of CDI patients. Importantly, these results suggest that continued nutritional support after successful treatment may be key to a full recovery.