Clostridioides difficile infection (CDI) causes alterations in the intestinal microbiota, frequently associated with changes in the gut metabolism of bile acids and cholesterol. In addition to the impact on microbiome composition and given the metabolic changes occurring during CDI, our work focuses on the importance to know the effects at the local and systemic levels, both during the infection and its treatment, by paying particular attention to plasma lipid metabolism due to its relationship with CDI pathogenesis. Specific changes, characterized by a loss of microbial richness and diversity and related to a reduction in short-chain acid-producing bacteria and an increase in bile salt hydrolase-producing bacteria, were observed in the gut microbiota of CDI patients, especially in those suffering from recurrent CDI (RCDI). However, gut microbiota showed its ability to restore itself after treatment, resembling healthy individuals, in those patients treated by fecal microbiome transfer (FMT), in contrast with those treated with antibiotics, and displaying increased levels of Eubacterium coprostanoligenes, a cholesterol-reducing anaerobe. Interestingly, changes in plasma lipidome revealed a global depletion in circulating lipids in CDI, with the largest impact on cholesteryl esters. CDI patients also showed a specific and consistent decrease in the levels of lipid species containing linoleic acid—an essential fatty acid—which were only partially recovered after antibiotic treatment. Analysis of the plasma lipidome reflects CDI impact on the gut microbiota and its metabolism, evidencing changes in sterol and fatty acid metabolism that are possibly related to specific alterations observed in gut microbial communities of CDI patients. IMPORTANCE: There is increasing evidence about the influence the changes in microbiota and its metabolism has on numerous diseases and infections such as Clostridioides difficile infection (CDI). The knowledge of these changes at local and systemic levels can help us manage this infection to avoid recurrences and apply the best therapies, such as fecal microbiota transfer (FMT). This study shows a better restoration of the gut in FMT-treated patients than in antibiotic-treated patients, resembling healthy controls and showing increased levels of cholesterol-reducing bacteria. Furthermore, it evidences the CDI impact on plasma lipidome. We observed in CDI patients a global depletion in circulating lipids, particularly cholesteryl esters, and a specific decrease in linoleic acid-containing lipids, an essential fatty acid. Our observations could impact CDI management because the lipid content was only partially recovered after treatment, suggesting that continued nutritional support, aiming to restore healthy lipid levels, could be essential for a full recovery.

An increasing prevalence and spread of Clostridioides difficile infection (CDI) caused by DH/NAP11/106/ST-42 has been observed worldwide, probably fostered by its great capacity to produce spores or by the higher resistance rates observed for some strains. Based on the results of our previous study where RT106 showed higher recurrence rates than other relevant ribotypes, a genetic analysis by whole-genome sequencing (WGS) of primary and recurrent RT106 isolates from ten patients was performed to determine whether the higher rate of recurrence associated with RT106 is due to relapses, caused by the same strain, or reinfections, caused by different strains. MLST profiles, resistance mutations, and phylogenetic relatedness were determined by comparative single nucleotide variant (SNV) analysis. All isolates were classified as ST42, and those belonging to the same patient were isogenic, with one exception; strains belonging to different patients were not with two exceptions, pointing to putative transmission events. Phylogenetic analysis also suggested the presence of similar local epidemic lineages associated with moxifloxacin resistance, except for one patient whose isolates clustered with different nonresistant US strains. Our results show that recurrent CDIs caused by RT06/ST42 are mainly due to relapses caused by the primary strains, showing the higher capacity of RT106/ST42 to persist and cause recurrences as compared to other ribotypes.

Clostridium difficile infection (CDI) was described in 1978 and soon became recognized as the main complication of antimicrobial use. In fact, one of the major risk factors associated with this infection is the use of antimicrobial agents ([1][1]). Clindamycin was the first antibiotic to be related

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.