Unraveling the Microbiome of Necrotizing Enterocolitis: Insights in Novel Microbial and Metabolomic Biomarkers.
Chiara Tarracchini, Christian Milani, Giulia Longhi, Federico Fontana, Leonardo Mancabelli, Roberta Pintus, Gabriele Andrea Lugli, Giulia Alessandri, Rosaria Anzalone, Alice Viappiani, Francesca Turroni, Michele Mussap, Angelica Dessì, Flaminia Cesare Marincola, Antonio Noto, Anna De Magistris, Marine Vincent, Sergio Bernasconi, Jean-Charles Picaud, Vassilios Fanos, Marco Ventura
Author Information
Chiara Tarracchini: Laboratory of Probiogenomics, Department of Chemistry, Life Sciences, and Environmental Sustainability, University of Parmagrid.10383.39, Parma, Italy.
Christian Milani: Laboratory of Probiogenomics, Department of Chemistry, Life Sciences, and Environmental Sustainability, University of Parmagrid.10383.39, Parma, Italy. ORCID
Giulia Longhi: Laboratory of Probiogenomics, Department of Chemistry, Life Sciences, and Environmental Sustainability, University of Parmagrid.10383.39, Parma, Italy.
Federico Fontana: Laboratory of Probiogenomics, Department of Chemistry, Life Sciences, and Environmental Sustainability, University of Parmagrid.10383.39, Parma, Italy.
Leonardo Mancabelli: Laboratory of Probiogenomics, Department of Chemistry, Life Sciences, and Environmental Sustainability, University of Parmagrid.10383.39, Parma, Italy.
Roberta Pintus: Neonatal Intensive Care Unit, Department of Surgical Sciences, University of Cagliarigrid.7763.5, Monserrato, Italy.
Gabriele Andrea Lugli: Laboratory of Probiogenomics, Department of Chemistry, Life Sciences, and Environmental Sustainability, University of Parmagrid.10383.39, Parma, Italy.
Giulia Alessandri: Laboratory of Probiogenomics, Department of Chemistry, Life Sciences, and Environmental Sustainability, University of Parmagrid.10383.39, Parma, Italy.
Rosaria Anzalone: GenProbio Srl, Parma, Italy.
Alice Viappiani: GenProbio Srl, Parma, Italy.
Francesca Turroni: Laboratory of Probiogenomics, Department of Chemistry, Life Sciences, and Environmental Sustainability, University of Parmagrid.10383.39, Parma, Italy. ORCID
Michele Mussap: Neonatal Intensive Care Unit, Department of Surgical Sciences, University of Cagliarigrid.7763.5, Monserrato, Italy.
Angelica Dessì: Neonatal Intensive Care Unit, Department of Surgical Sciences, University of Cagliarigrid.7763.5, Monserrato, Italy.
Flaminia Cesare Marincola: Department of Chemical and Geological Sciences, University of Cagliarigrid.7763.5, Monserrato, Cagliari, Italy.
Antonio Noto: Department of Medical Science and Public Health, University of Cagliarigrid.7763.5, Monserrato, Cagliari, Italy.
Anna De Magistris: Neonatal Intensive Care Unit, Department of Surgical Sciences, University of Cagliarigrid.7763.5, Monserrato, Italy.
Marine Vincent: Neonatology Unit, Croix-Rousse University Hospital, Hospices Civils de Lyongrid.413852.9, Lyon, France.
Sergio Bernasconi: Microbiome Research Hub, University of Parmagrid.10383.39, Parma, Italy.
Jean-Charles Picaud: Neonatology Unit, Croix-Rousse University Hospital, Hospices Civils de Lyongrid.413852.9, Lyon, France.
Vassilios Fanos: Neonatal Intensive Care Unit, Department of Surgical Sciences, University of Cagliarigrid.7763.5, Monserrato, Italy.
Marco Ventura: Laboratory of Probiogenomics, Department of Chemistry, Life Sciences, and Environmental Sustainability, University of Parmagrid.10383.39, Parma, Italy. ORCID
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 NECinfants. 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. 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 genus members in the progression of NEC. Remarkably, our analyses highlighted a gastrointestinal DL-lactate accumulation among NECpatients that might represent a novel potential functional biomarker for the early diagnosis of NEC.
