Clostridia in Premature Neonates' Gut: Incidence, Antibiotic Susceptibility, and Perinatal Determinants Influencing Colonization

Although premature neonates (PN) gut microbiota has been studied, data about gut clostridial colonization in PN are scarce. Few studies have reported clostridia colonization in PN whereas Bacteroides and bifidobacteria have been seldom isolated. Such aberrant gut microbiota has been suggested to be a risk factor for the development of intestinal infections. Besides, PN are often treated by broad spectrum antibiotics, but little is known about how antibiotics can influence clostridial colonization based on their susceptibility patterns. The aim of this study was to report the distribution of Clostridium species isolated in feces from PN and to determine their antimicrobial susceptibility patterns. Additionally, clostridial colonization perinatal determinants were analyzed.Of the 76 PN followed until hospital discharge in three French neonatal intensive care units (NICUs), 79% were colonized by clostridia. Clostridium sp. colonization, with a high diversity of species, increased throughout the hospitalization. Antibiotic courses had no effect on the clostridial colonization incidence although strains were found susceptible (except C. difficile) to anti-anaerobe molecules tested. However, levels of colonization were decreased by either antenatal or neonatal (during more than 10 days) antibiotic courses (p = 0.006 and p = 0.001, respectively). Besides, incidence of colonization was depending on the NICU (p = 0.048).This study shows that clostridia are part of the PN gut microbiota. It provides for the first time information on the status of clostridia antimicrobial susceptibility in PN showing that strains were susceptible to most antibiotic molecules. Thus, the high prevalence of this genus is not linked to a high degree of resistance to antimicrobial agents or to the use of antibiotics in NICUs. The main perinatal determinant influencing PN clostridia colonization appears to be the NICU environment

Constipation de l'enfant et sa prise en charge

PARIS6-Bibl. St Antoine CHU (751122104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Les nouvelles approches thérapeutiques dans la prise en charge de l'allergie aux protéines de lait de vache chez l'enfant

PARIS-BIUP (751062107) / SudocSudocFranceF

Pancréatite chronique et mutations génétiques (à propos d'une observation pédiatrique)

[Résumé français]La pancréatique chronique héréditaire (PCH) est une des principales étiologies des pancréatiques chroniques (PC) de l'enfant. La présentation est une observation pédiatrique rapportant une histoire familiale de PCH associée à une délétion -33 du trypsinogène cationique (-33 DEL TCC). Les travaux récents ont montré que la PCH est une pathologie rare à transmission autosomique dominante de pénétrance et d'expressivité variables. Les mutations de 3 gènes sont associées à un risque accru de pancréatite aiguë ou chronique : le gène du trypsinogène cationique (PRSS1), le gène de l'inhibiteur trypsique sécrétoire pancréatique (PSTI) aussi appelé inhibiteur de protéase à sérine Kazal de type 1 (SPINK1) et le gène du régulateur de la perméabilité transmembranaire de la fibrose kystique (CFTR). Le modèle physiopathologique est une autodigestion du parenchyme pancréatique liée à une altération des mécanismes de défense contre l'activation précoce et inappropriée de la trypsine.PARIS13-BU Serge Lebovici (930082101) / SudocSudocFranceF

Coprologie du nouveau-né prématuré (étude des marqueurs inflammatoires, du microbiote intestinal et de sa modulation par un lait fermenté sans bactéries vivantes)

L immaturité intestinale du nouveau-né prématuré ainsi que le retard d implantation du microbiote intestinal l expose à des complications majeures comme l entéropathie ou l entérocolite ulcéro-nécrosante qui sont des pathologies à morbidité et mortalité élevées. Nous avons travaillé sur le développement d outils biologiques non invasifs permettant l évaluation de la fonction digestive. Nous avons montré que la calprotectine fécale, marqueur de l inflammation intestinale, est physiologiquement élevée dans cette population et avons défini des valeurs seuils en fonction de la gravité de l atteinte intestinale. Nous avons décrit l établissement du microbiote intestinal qui se traduit par un retard important de la colonisation d origine entérique, concernant en particulier les bifidobactéries. Enfin, nous avons testé pour la 1ère fois, un lait fermenté sans bactéries vivantes. Cette formule semble réduire les ballonnements abdominaux et diminuer l inflammation de la muqueuse intestinale.Due to the intestinal immaturity and to the delayed gut microbiota implantation, premature neonates are exposed to intestinal complications such as enteropathy or necrotizing enterocolitis with high morbidity and mortality. We focused our research on the preterm gut, developing the coprology analyses of the premature neonate in order to be the least invasive. We showed that faecal calprotectin is physiologically high in this population and defined cut-off values for the development of intestinal diseases according to their severity. We confirmed a delayed colonization of the normal microbiota and we showed that a threshold birth age of 33 weeks of gestation is a condition for colonization by bifidobacteria. For the first time we have tested a fermented preterm formula without live bacteria. This formula is safe and well tolerated and seems to reduce both abdominal distension and inflammation of the intestinal mucosa.PARIS-BIUP (751062107) / SudocSudocFranceF

Editorial: Probiotics in Children Health

There is a growing body of evidence linking human health to the activity and composition 83 of gut microbiota as well as its alteration to intestinal and systemic diseases. In the last 84 years, functional gastrointestinal disorders, inflammatory, allergic, and autoimmune conditions, 85 metabolic syndrome, and neurological and behavioral diseases have all been associated with 86 microbiota unbalance, the so-called “dysbiosis” . The perinatal period and early life should be 87 considered as extremely vulnerable ages for the establishment of physiological microbiota and its 88 consequent programming of immune and metabolic responses

Putting undergraduate medical students in AI-CDSS designers’ shoes: An innovative teaching method to develop digital health critical thinking

International audienceIntroductionDigital health programs are urgently needed to accelerate the adoption of Artificial Intelligence and Clinical Decision Support Systems (AI-CDSS) in clinical settings. However, such programs are still lacking for undergraduate medical students, and new approaches are required to prepare them for the arrival of new and unknown technologies. At University Paris Cité medical school, we designed an innovative program to develop the digital health critical thinking of undergraduate medical students that consisted of putting medical students in AI-CDSS designers’ shoes.MethodsWe followed the six steps of Kern’s approach for curriculum development: identification of needs, definition of objectives, design of an educational strategy, implementation, development of an assessment and design of program evaluation.ResultsA stand-alone and elective AI-CDSS program was implemented for fourth-year medical students. Each session was designed from an AI-CDSS designer viewpoint, with theoretical and practical teaching and brainstorming time on a project that consisted of designing an AI-CDSS in small groups. From 2021 to 2022, 15 students were enrolled: they rated the program 4.4/5, and 80% recommended it. Seventy-four percent considered that they had acquired new skills useful for clinical practice, and 66% felt more confident with technologies. The AI-CDSS program aroused great enthusiasm and strong engagement of students: 8 designed an AI-CDSS and wrote two scientific 5-page articles presented at the Medical Informatics Europe conference; 4 students were involved in a CDSS research project; 2 students asked for a hospital internship in digital health; and 1 decided to pursue PhD training.DiscussionPutting students in AI-CDSS designers’ shoes seemed to be a fruitful and innovative strategy to develop digital health skills and critical thinking toward AI technologies. We expect that such programs could help future doctors work in rapidly evolving digitalized environments and position themselves as key leaders in digital health

Assessment of local and systemic signature of eosinophilic esophagitis (EoE) in children through multi-omics approaches

BackgroundEosinophilic oesophagitis (EoE) is a chronic food allergic disorder limited to oesophageal mucosa whose pathogenesis is still only partially understood. Moreover, its diagnosis and follow-up need repeated endoscopies due to absence of non-invasive validated biomarkers. In the present study, we aimed to deeply describe local immunological and molecular components of EoE in well-phenotyped children, and to identify potential circulating EoE-biomarkers.MethodsBlood and oesophageal biopsies were collected simultaneously from French children with EoE (n=17) and from control subjects (n=15). Untargeted transcriptomics analysis was performed on mRNA extracted from biopsies using microarrays. In parallel, we performed a comprehensive analysis of immune components on both cellular and soluble extracts obtained from both biopsies and blood, using flow cytometry. Finally, we performed non-targeted plasma metabolomics using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). Uni/multivariate supervised and non-supervised statistical analyses were then conducted to identify significant and discriminant components associated with EoE within local and/or systemic transcriptomics, immunologic and metabolomics datasets. As a proof of concept, we conducted multi-omics data integration to identify a plasmatic signature of EoE.ResultsFrench children with EoE shared the same transcriptomic signature as US patients. Network visualization of differentially expressed (DE) genes highlighted the major dysregulation of innate and adaptive immune processes, but also of pathways involved in epithelial cells and barrier functions, and in perception of chemical stimuli. Immune analysis of biopsies highlighted EoE is associated with dysregulation of both type (T) 1, T2 and T3 innate and adaptive immunity, in a highly inflammatory milieu. Although an immune signature of EoE was found in blood, untargeted metabolomics more efficiently discriminated children with EoE from control subjects, with dysregulation of vitamin B6 and various amino acids metabolisms. Multi-blocks integration suggested that an EoE plasma signature may be identified by combining metabolomics and cytokines datasets.ConclusionsOur study strengthens the evidence that EoE results from alterations of the oesophageal epithelium associated with altered immune responses far beyond a simplistic T2 dysregulation. As a proof of concept, combining metabolomics and cytokines data may provide a set of potential plasma biomarkers for EoE diagnosis, which needs to be confirmed on a larger and independent cohort

Isolation and Characterization of Commensal Bifidobacteria Strains in Gut Microbiota of Neonates Born Preterm: A Prospective Longitudinal Study

Bifidobacterial population dynamics were investigated using a longitudinal analysis of dominant species isolated from feces of neonates born preterm (singletons (n = 10), pairs of twins (n = 11)) from birth up to 16 months of age. We performed quantification, isolation, and identification of the dominant bifidobacteria strains. The genetic relationship of the isolates was investigated via pulsed field gel electrophoresis (PFGE) genotyping, and PCR was used to screen the specific genetic marker tet genes. Additionally, all of the isolated strains were phenotypically characterized by their response to gastro-intestinal stresses and the MIC determination of tetracycline. In the same individual, our results showed a turnover of the bifidobacteria dominant population not only at species but also at strain levels. In addition, we found clonally related strains between twins. A minority of strains were tolerant to gastric (6%) and intestinal (16%) stresses. Thirteen percent of the strains were resistant to tetracycline. This work is original as it provides insights at the strain level of the early life in vivo dynamics of gut microbiota bifidobacteria in preterm neonates. It highlights the need to take into consideration the fluctuation of bifidobacteria populations that may occur for one individual

Conditions of bifidobacterial colonization in preterm infants: A prospective analysis

Background: Premature birth results in a delayed and abnormal qualitative pattern of gut colonization. This abnormal pattern is thought to affect intestinal development and contribute to a higher risk of gastrointestinal infectious diseases such as neonatal necrotizing enterocolitis (NEC). In particular, bifidobacteria are thought to play a major role. We therefore studied bifidobacterial colonization in preterm infants during the first month of life. Patients and Methods: Fecal samples were prospectively analyzed in 52 infants born at a gestational age ranging from 30 to 35 weeks fed with a preterm formula alone and, in 18, with their mother's milk. Fecal samples were collected twice per week during the hospital stay. Bifidobacterial colonization was analyzed with culture and a molecular method. Results: Bifidobacterial colonization occurred in 18 infants at a median age of 11 days, always greater than the corrected mean gestational age of 35.4 weeks (SD, 0.9) and greater than 34 weeks for 16 of 18. Colonization by bifidobacteria was affected by neither birthweight nor mode of delivery nor antibiotics given to the mother or infant. In contrast, birth gestational age had a significant impact on colonization by bifidobacteria (P < 0.05), which always occurred in children born at a birth gestational age greater than 32.9 weeks (P < 0.05). Conclusions: Birth gestational age seems to act as a major determinant of bifidobacterial colonization in the premature infant, suggesting the role of gut maturation, a finding that should probably be taken into account in manipulations of the gut flora aimed at reducing NEC