This study investigates the persistence of gut fungal (mycobiome) dysbiosis in patients with sepsis or trauma, particularly those experiencing chronic critical illness (CCI). The research reveals that the mycobiome in CCI patients shifts toward a pathobiome state, which is more susceptible to infection. The fungal community in these patients is dominated by Candida spp., while commensal fungal species are depleted. These changes correlate with alterations in the gut's micro-ecological niche, involving specific gut bacteria and gut-blood metabolites. The findings highlight the need to assess and address the increased risk of fungal infections in CCI patients. The gut mycobiome, though smaller than the bacterial microbiome, plays a crucial role in maintaining gut homeostasis. Dysbiosis in the mycobiome has been linked to various diseases, including inflammatory bowel disease, irritable bowel syndrome, and colorectal cancer. In critically ill patients, dysbiosis in the gut microbiome is associated with increased susceptibility to infections, recurrence of sepsis, and multiorgan dysfunction syndrome. Antibiotics used to treat sepsis and trauma patients can disrupt the gut microbiome, leading to an increased risk of fungal infections. The study found that the mycobiome of sepsis and trauma patients shifts toward a pathobiome state dominated by Candida spp., with concurrent alterations in the bacteriome-metabolome micro-ecological niches. The findings suggest that the dysbiosis in the mycobiome persists even up to two weeks post-sepsis and trauma, emphasizing the need for targeted interventions to reduce the risk of subsequent fungal infections. The study also highlights the importance of considering sex differences in microbial diversity, with male patients showing more severe dysbiosis than female patients. The research underscores the need for further studies to explore novel approaches to minimize the incidence of fungal infections and develop therapeutic interventions aimed at preventing dysbiosis and restoring gut micro-ecological homeostasis. The findings suggest that targeting the mycobiome dysbiosis could be a viable focus for therapeutic regimens aimed at reducing the risk of subsequent fungal infections.This study investigates the persistence of gut fungal (mycobiome) dysbiosis in patients with sepsis or trauma, particularly those experiencing chronic critical illness (CCI). The research reveals that the mycobiome in CCI patients shifts toward a pathobiome state, which is more susceptible to infection. The fungal community in these patients is dominated by Candida spp., while commensal fungal species are depleted. These changes correlate with alterations in the gut's micro-ecological niche, involving specific gut bacteria and gut-blood metabolites. The findings highlight the need to assess and address the increased risk of fungal infections in CCI patients. The gut mycobiome, though smaller than the bacterial microbiome, plays a crucial role in maintaining gut homeostasis. Dysbiosis in the mycobiome has been linked to various diseases, including inflammatory bowel disease, irritable bowel syndrome, and colorectal cancer. In critically ill patients, dysbiosis in the gut microbiome is associated with increased susceptibility to infections, recurrence of sepsis, and multiorgan dysfunction syndrome. Antibiotics used to treat sepsis and trauma patients can disrupt the gut microbiome, leading to an increased risk of fungal infections. The study found that the mycobiome of sepsis and trauma patients shifts toward a pathobiome state dominated by Candida spp., with concurrent alterations in the bacteriome-metabolome micro-ecological niches. The findings suggest that the dysbiosis in the mycobiome persists even up to two weeks post-sepsis and trauma, emphasizing the need for targeted interventions to reduce the risk of subsequent fungal infections. The study also highlights the importance of considering sex differences in microbial diversity, with male patients showing more severe dysbiosis than female patients. The research underscores the need for further studies to explore novel approaches to minimize the incidence of fungal infections and develop therapeutic interventions aimed at preventing dysbiosis and restoring gut micro-ecological homeostasis. The findings suggest that targeting the mycobiome dysbiosis could be a viable focus for therapeutic regimens aimed at reducing the risk of subsequent fungal infections.