Unraveling the Microbiome of Necrotizing Enterocolitis: Insights in Novel Microbial and Metabolomic Biomarkers

Microbiology Spectrum

Flaminia Cesare Marincola¹  Antonio Noto²  Rosaria Anzalone³  Alice Viappiani³  Francesca Turroni⁴  Gabriele Andrea Lugli⁴  Marco Ventura⁴  Christian Milani⁴  Chiara Tarracchini⁴  Giulia Longhi⁴  Federico Fontana⁴  Leonardo Mancabelli⁴  Giulia Alessandri⁴  Sergio Bernasconi⁵  Vassilios Fanos⁶  Michele Mussap⁶  Angelica Dessì⁶  Roberta Pintus⁶  Anna De Magistris⁶  Jean-Charles Picaud⁷  Marine Vincent⁷ 

[1] Department of Chemical and Geological Sciences, University of Cagliari, Monserrato, Cagliari, Italy;Department of Medical Science and Public Health, University of Cagliari, Monserrato, Cagliari, Italy;GenProbio Srl, Parma, Italy;Laboratory of Probiogenomics, Department of Chemistry, Life Sciences, and Environmental Sustainability, University of Parma, Parma, Italy;Microbiome Research Hub, University of Parma, Parma, Italy;Neonatal Intensive Care Unit, Department of Surgical Sciences, University of Cagliari, Monserrato, Italy;Neonatology Unit, Croix-Rousse University Hospital, Hospices Civils de Lyon, Lyon, France;

关键词: necrotizing enterocolitis;    NEC;    microbiota;    metagenomics;    shotgun;   

DOI  :  10.1128/Spectrum.01176-21

来源: DOAJ

【 摘 要 】

ABSTRACT Necrotizing enterocolitis (NEC) is among the most relevant gastrointestinal diseases affecting mostly prematurely born infants with low birth weight. While intestinal dysbiosis has been proposed as one of the possible factors involved in NEC pathogenesis, the role of the gut microbiota remains poorly understood. In this study, the gut microbiota of preterm infants was explored to highlight differences in the composition between infants affected by NEC and infants prior to NEC development. A large-scale gut microbiome analysis was performed, including 47 shotgun sequencing data sets generated in the framework of this study, along with 124 retrieved from publicly available repositories. Meta-analysis led to the identification of preterm community state types (PT-CSTs), which recur in healthy controls and NEC infants. Such analyses revealed an overgrowth of a range of opportunistic microbial species accompanying the loss of gut microbial biodiversity in NEC subjects. Moreover, longitudinal insights into preterm infants prior to NEC development indicated Clostridium neonatale and Clostridium perfringens species as potential biomarkers for predictive early diagnosis of this disease. Furthermore, functional investigation of the enzymatic reaction profiles associated with pre-NEC condition suggested DL-lactate as a putative metabolic biomarker for early detection of NEC onset. IMPORTANCE Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease occurring predominantly in premature infants whose etiology is still not fully understood. In this study, the analysis of infant fecal samples through shotgun metagenomics approaches revealed a marked reduction of the intestinal (bio)diversity and an overgrowth of (opportunistic) pathogens associated with the NEC development. In particular, dissection of the infant’s gut microbiome before NEC diagnosis highlighted the potential involvement of Clostridium genus members in the progression of NEC. Remarkably, our analyses highlighted a gastrointestinal DL-lactate accumulation among NEC patients that might represent a novel potential functional biomarker for the early diagnosis of NEC.

【 授权许可】

Unknown