Unraveling Cecal\nAlterations in <i>Clostridioides\ndifficile</i> Colonized Mice through Comprehensive Metabolic\nProfiling

The disruption of\ngut microbiota caused by antibiotics favors the\nintestinal colonization of <i>Clostridioides difficile</i> – a Gram-positive, spore-forming anaerobic bacterium that\ncauses potentially fatal gastrointestinal infections. In an endeavor\nto elucidate the complexities of the gut-brain axis in the context\nof <i>Clostridium difficile</i> infection (CDI), a murine\nmodel has been used to investigate the potential effects of antibiotic\nadministration and subsequent colonization by <i>C. difficile</i>, as well as the impact of three different 10-day treatments (metronidazole,\nprobiotics, and fecal microbiota transplantation), on the cecal metabolome\nfor the first time. This follows our previous research which highlighted\nthe metabolic effect of CDI and these treatments in the brain and\nemploys the same four different metabolomics-based methods (targeted\nGC-MS/MS, targeted HILIC-MS/MS, untargeted RP-LC-HRMS/MS and untargeted\nGC-MS). A total of 286 unique metabolites have been identified in\nthe mouse cecal profiles and statistical analysis revealed that CDI,\nas well as the subsequent treatments, significantly alters cecal metabolites\nand lipids implicated in various biochemical pathways centered around\namino acid metabolism, glycerophospholipid metabolism, and central\ncarbon metabolism. To our knowledge, this study represents the first\nexploration of the effects of <i>C. difficile</i>-induced\ncolitis and potential treatments on the cecal tissue metabolome.