Dysbiose associée aux antibiotiques chez l’enfant. Quelles conséquences ? Quels moyens de prévention ?

Le développement des antibiotiques est considéré comme l’une des plus grandes avancées médicales du XXe siècle mais ces traitements ne sont pas dépourvus d’effets indésirables chez l’enfant, surtout dans la tranche d’âge 0-2 ans, dont la diarrhée associée aux antibiotiques (DAA). La DAA serait provoquée par une perturbation du microbiote, ou dysbiose, c’est-à-dire une altération de la composition intestinale en termes du nombre d’organismes, de la diversité et de la richesse génique et par conséquence de sa fonction. Il est estimé que la DAA affecte jusqu’à 40% des enfants traités par des antibiotiques à large spectre. Qui plus est, une dysbiose qui se produit au cours des 1000 premiers jours de vie de l’enfant peut être associée à la pathogénèse de maladies intestinales et extra-intestinales plus tard pendant l'enfance voire à l’âge adulte. Même si l'utilisation restreinte et rationnelle des antibiotiques est le meilleur moyen de réduire le risque de la DAA et de la dysbiose, l’état du microbiote intestinal peut être amélioré par des pratiques préventives, telles qu’un régime alimentaire diversifié et le traitement par probiotiques. De nombreuses revues systématiques et méta-analyses d’essais cliniques sur les probiotiques ont confirmé l’efficacité de l’utilisation de certaines souches probiotiques dans le traitement et même la prévention des DAA chez l’adulte et l’enfant. C’est le cas pour la levure Saccharomyces boulardii (S. boulardii) ou la bactérie Lactobacillus rhamnosus GG (L rhamnosus GG) particulièrement. Par exemple, l’ESPGHAN (European Society for Paediatric Gastroenterology, Hepatology and Nutrition) recommande chez les enfants hospitalisés ou en ambulatoire présentant des facteurs de risque de DAA d’administrer des doses suffisantes (≥5 milliards d’UFC par jour) de souches spécifiques de Saccharomyces boulardii (comme la souche CNCM I-745) ou de L rhamnosus GG dès le début du traitement antibiotique. Afin d’étayer encore ces recommandations, il est nécessaire que des essais cliniques apportent des données probantes sur le traitement des enfants par les souches autorisées

Interplay Between Exercise and Gut Microbiome in the Context of Human Health and Performance

Gut microbiota and exercise have recently been shown to be interconnected. Both moderate and intense exercise are typically part of the training regimen of endurance athletes, but they exert different effects on health. Moderate exercise has positive effects on the health of average athletes, such as a reduction in inflammation and intestinal permeability and an improvement in body composition. It also induces positive changes in the gut microbiota composition and in the microbial metabolites produced in the gastrointestinal tract. Conversely, intense exercise can increase gastrointestinal epithelial wall permeability and diminish gut mucus thickness, potentially enabling pathogens to enter the bloodstream. This, in turn, may contribute to the increase in inflammation levels. However, elite athletes seem to have a higher gut microbial diversity, shifted toward bacterial species involved in amino acid biosynthesis and carbohydrate/fiber metabolism, consequently producing key metabolites such as short-chain fatty acids. Moreover, rodent studies have highlighted a bidirectional relationship, with exercise impacting the gut microbiota composition while the microbiota may influence performance. The present review focuses on gut microbiota and endurance sports and how this interconnection depends upon exercise intensity and training. After pointing out the limits of the studies so far available, we suggest that taking into account the microbiota composition and its metabolic contribution to human host health could help in monitoring and modulating athletes' health and performance. Such an integrated approach should help in the design of microbiome-based solutions for health or performance

SYNBIOTICS IN THE MANAGEMENT OF PEDIATRIC GASTROINTESTINAL DISORDERS: POSITION PAPER OF THE ESPGHAN SPECIAL INTEREST GROUP ON GUT MICROBIOTA AND MODIFICATIONS

Synbiotics are a mixture comprising of live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host. There is an increasing number of studies investigating their role in different diseases and disorders

Physician Global Assessment International Standardisation COnsensus in Systemic Lupus Erythematosus: the PISCOS study

The Physician Global Assessment International Standardisation COnsensus in Systemic Lupus Erythematosus (PISCOS) study aimed to obtain an evidence-based and expert-based consensus standardisation of the Physician Global Assessment (PGA) scoring of disease activity in systemic lupus erythematosus (SLE). An international panel of 79 SLE experts participated in a three-round Delphi consensus process, in which 41 statements related to the PGA in SLE were rated, using a 0 (strongly disagree) to 10 (strongly agree) numerical rating scale. Statements with agreement of 75% or greater were selected and further validated by the expert panel. Consensus was reached on 27 statements, grouped in 14 recommendations, for the use of the PGA in SLE, design of the PGA scale, practical considerations for PGA scoring, and the relationship between PGA values and levels of disease activity. Among these recommendations, the expert panel agreed that the PGA should consist of a 0-3 visual analogue scale for measuring disease activity in patients with SLE in the preceding month. The PGA is intended to rate the overall disease activity, taking into account the severity of active manifestations and clinical laboratory results, but excluding organ damage, serology, and subjective findings unrelated to disease activity. The PGA scale ranges from "no disease activity" (0) to the "most severe disease activity" (3) and incorporates the values 1 and 2 as inner markers to categorise disease activity as mild (>= 0.5 to 1), moderate (>1 and <= 2) and severe (>2 to 3). Only experienced physicians can rate the PGA, and it should be preferably scored by the same rater at each visit. The PISCOS results will allow for increased homogeneity and reliability of PGA ratings in routine clinical practice, definitions of remission and low disease activity, and future SLE trials

Functional abdominal pain disorders and patient- and parent- reported outcomes in children with inflammatory bowel disease in remission

BACKGROUND: Chronic abdominal pain occurs frequently in pediatric patients with inflammatory bowel disease (IBD) in remission. AIMS: To assess the prevalence and factors associated with Functional Abdominal Pain Disorders among IBD children in remission (IBD-FAPD). METHODS: Patients with IBD for > 1 year, in clinical remission for ≥ 3 months were recruited from a National IBD network. IBD-FAPDs were assessed using the Rome III questionnaire criteria. Patient- or parent- reported outcomes were assessed. RESULTS: Among 102 included patients, 57 (56%) were boys, mean age (DS) was 15.0 (± 2.0) years and 75 (74%) had Crohn's disease. Twenty-two patients (22%) had at least one Functional Gastrointestinal Disorder among which 17 had at least one IBD-FAPD. Past severity of disease or treatments received and level of remission were not significantly associated with IBD-FAPD. Patients with IBD-FAPD reported more fatigue (peds-FACIT-F: 35.9 ± 9.8 vs. 43.0 ± 6.9, p = 0.01) and a lower HR-QoL (IMPACT III: 76.5 ± 9.6 vs. 81.6 ± 9.2, p = 0.04) than patients without FAPD, and their parents had higher levels of State and Trait anxiety than the other parents. CONCLUSIONS: Prevalence of IBD-FAPD was 17%. IBD-FAPD was not associated with past severity of disease, but with fatigue and lower HR-QoL

Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research