The Gut as a Source of Infection for Fungal Pathogens: Increased Fecal Candida albicans Precedes Onset of Candida Late-Onset Sepsis in Very Preterm Infants
Year: 2025
Type: article
Study design: Observational Study
Abstract: BACKGROUND: The skin-to-blood route is traditionally considered the main pathway in Candida late-onset sepsis (LOS) development in preterm infants. However, emerging evidence suggests that the gut also serves as a source of infection. We aimed to characterize fecal mycobiota and microbiota profiles preceding onset of Candida LOS to assess the role of the preterm gut microbiome in disease development. METHODS: This multicenter case-control study included very preterm infants (<30 weeks of gestation) with Candida LOS. Each case was matched to nonaffected controls by gestational and postnatal age, hospital site, and/or cumulative antibiotic exposure prior to day of LOS onset (t = 0). Fecal samples collected at t = 0 and the 5 preceding days were analyzed by ITS1 and 16S RNA sequencing. Microbial amplicon yields, composition, and interkingdom correlations were assessed. RESULTS: Of 2397 screened infants, fecal samples were available for 8 of 19 infants with Candida LOS. In these 8 cases, the ITS/16S amplicon yield ratio was increased (P < .001), and the relative abundance of fecal Candida albicans correlated positively with fungal amplicon yield (ρ = 0.71, adjusted P = .005), suggesting increased absolute abundance up to 5 days before onset. Additionally, bacterial yields were significantly lower (P = .02) and α-diversity significantly decreased (P = .012) when compared to the controls. CONCLUSIONS: Increased fecal C albicans preceded Candida LOS onset, implicating the preterm gut as a potential source of infection. Reduced bacterial yields and diversity suggest ecological alterations that may facilitate Candida pathogenicity in the preterm gut. These findings support further research into gut-derived Candida LOS and the potential for microbiota-targeted prevention strategies.
Authors: Rimke R de Kroon, Irini A M Kreulen, Mark Davids, Isabelle A M van Thiel, Iris Admiraal, Xanthe Verdoes, Mirjam M van Weissenbruch, Hendrik J Niemarkt, Wouter J de Jonge, Tim de Meij, the generation P study group, Chris H P van den Akker, Aranka J van Wesemael, Nina M Frerichs, Marlou M A Kouwenberg-Raets, Christian V Hulzebos, Willem P de Boode, Marijn J Vermeulen, Daniel C Vijlbrief, Veerle Cossey
Institutions: Emma Kinderziekenhuis, Amsterdam University Medical Centers, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC Location University of Amsterdam, University of Amsterdam, Vrije Universiteit Amsterdam, Máxima Medisch Centrum, Eindhoven University of Technology, University Hospital Bonn
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,763
Funder: Ministère de l'Intérieur
OpenAlex ID: W4415035233