Objectives and Study

Our aim was to study the link between Bifidobacterium abundance and antibiotic resistance load in gut microbiota of infant early in life, and also to ascertain the potential factors that may contribute to the antibiotic resistance acquisition

Methods

101 infants at 1 month of age from the MAMI birth cohort were included in the study. Maternal-neonatal clinical records were available. Microbiota profiling was carried out by 16S rRNA gene amplicon (V3-V4 region) sequencing in Illumina Platform. Targeted antibiotic resistance genes (ARGs) including tetM, tetW, tetO, blaTEM, blaSHV and ermB were quantified by qPCR. All statistical analyses were performed with R version 3.6.0.

Results

Infant microbiota was clustered in two different groups according to their Bifidobacterium genus abundance (54% for cluster high and 9% for cluster low). Microbiota composition differed significantly between both groups (p=0.001) in terms of beta-diversity. Lower abundance of Bifidobacterium in the infant gut was associated with higher load of antibiotic resistant genes. The most abundant ARGs were tetW and tetM, followed by beta-lactams (bla genes). Microbiota of the cluster Low was characterized by the presence of Blautia, Enterococcus, Veilonella, Phocaelcola, Streptococcus, Escherichia/Shigella, Klebsiella and Bacteroides, being these last three genera positively correlated with copies of tetO, tetM, blaTEM, blaSHV and ermB resistant genes. Random decision forest showed that antibiotic exposure during the first month of life is the factor that can explain the better this association.

Conclusions

Our results highlight the relevance of Bifidobacterium species in the early acquisition and establishment of antibiotic resistances in the gut. Further studies are needed to develop potential strategies to favour the adequate early colonization and fight against the spread of antibiotic resistances with effects on human health.

Objectives and Study

Objectives: To study gut microbiome, inflammasome, and microbial metabolome in stools of children recently diagnosed with cow's milk (CM) protein-induced enterocolitis syndrome (CM-FPIES) searching for pathophysiology or diagnostic biomarkers

Methods

Methods: Observational, prospective, multicenter, controlled study. Inclusion criteria: CM-FPIES children under 2 years of age. Control Group: healthy infants, < 12 months of age, who had not received antibiotics and/or probiotics in the 2 preceding weeks. Stools were collected fresh, within two weeks after dietary removal of CM proteins, in a special container (Gut-Alive®) and sent to the central laboratory. Analysis of intestinal microbiome by metagenomics (shotgun sequencing), determination of fecal calprotectin (FC) by ELISA, quantification of short-chain fatty acids (SCFA) by gas chromatography, and quantification of immune mediators by multiplex system were performed. Statistical analysis: non-parametric Mann-Whitney U tests

Results

Results: Seven CM-FPIES cases (5 males) aged from 9 days to 14 months (median 4 months) and 14 controls (4 males, median age 5 months) from 5 hospitals and one primary care clinic were included. While controls showed higher abundance of Bifidobacteria (79 vs 44%), patients showed higher frequency of Enterobacteria sequences, specifically of Escherichia coli genes. CM-FPIES patients had higher FC levels (216.5 vs 92.8 mcg/g; p=0.2). Significant increase in SCFA excretion was observed in CM-FPIES (acetic, propionic and butyric p<0.001; isovaleric, isobutyric, caproic p=0.015). Lower levels of interferon-gamma-inducible protein 10 (0.85 vs 1.7 pg/ml; p=0.088) and lower levels of IL-1 receptor antagonist (11.1 vs. 5.3 pg/ml; p=0.015). were observed in CM-FPIES patients. Finally, while in controls, levels of 8.50 pg/mL of platelet-derived growth factor were observed in stools, they were undetectable in patients (detection limit 0.180 pg/ml).

Conclusions

Conclusions: There are striking differences in composition of fecal microbiome at diagnosis in patients with CM-FPIES. Observed differences in metabolome and inflammasome may be useful to gain insight into FPIES pathophysiology and early diagnosis.

Objectives and Study

In the presence of the post-traumatic stress disorder (PTSD), with taking into account the key role of the gut-brain axis in the regulation of the digestive processes, a special attention should be paid to gastrointestinal manifestations.

To determine the features of gastroenterological manifestations and nutrition in children with PTSD.

Methods

We examined 314 children aged 5–10 years. All children were in the rehabilitation centre after their displacement caused by the war. For the study, a special questionnaire was suggested consisting of 30 questions about the digestive system and nutrition.

Results

The most common digestive problems in children with PTSD were abdominal pain (41.1±2.8)%, stool disorder with a tendency to constipation (32.5±2.6)%, nausea (16.9±2.1)%. It was determined that functional gastrointestinal disorders (74.2±2.5)% prevailed among gastroenterological diseases, namely functional disorders of the gallbladder – (68.8±2.6)%, irritable bowel syndrome with constipation – (38.9±2.8)%, functional dyspepsia – (10.2±1.7)%, cyclic vomiting syndrome – (6.1±1.4)%. Exacerbation of chronic gastrointestinal pathology was revealed in (25.8±2.5)% of children: chronic gastroduodenitis – (62.4±2.7)%, gastroesophageal reflux disease – (44.9±2.8)%, chronic cholecystitis – (31.5±2.6)%.

Among the concomitant symptoms in children, asthenoneurotic disorders prevailed: deterioration in school performance (74.8±2.5)%, irritability (69.4±2.6)%, depressed mood (67.2±2.6)%, excessive tearfulness (65.9±2.7)%, overfatigue (87.3±1.9)%, sleep disturbance (63.1±2.7)%, social self-isolation (57.6±2.8)%.

The study revealed that (58.3±2.8)% of children with PTSD experienced changes in eating behavior, such as decreased appetite (43.0±2.8)%, food refusal (4.8±1.2)%, unusual taste preferences – (9.2±1.6)%. The consumption of sweets – (40.8±2.8)%, the forced consumption of fast food – (31.5±2.6)% and the frequency of snacks – (27.1±2.5)% used for stress relief in children.

Conclusions

Digestive and eating disorders are common manifestations of PTSD in children. As a result, the priority of preserving the health of children under condition of a military conflict is necessity in maintaining adequate nutritional support, observing the diet with the active involvement of psychocorrective measures.

Objectives and Study

Very early onset inflammatory bowel disease (VEOIBD) is associated with unique disease course and distinct endoscopic features. The aim of this study is to describe the endoscopic and histologic features of patients with VEOIBD from a tertiary medical center on a large cohort.

Methods

We retrospectively reviewed medical records of VEOIBD patients in a decade from 2011 to 2021. Clinical data, including disease phenotypes, endoscopic and histologic findings were retrieved from medical records. Next generation sequencing was performed.

Results

225 VEOIBD subjects were included in this study. Monogenic defects were identified in 161 subjects. Monogenic IBD patients more commonly had CD-like disease. Colonic diseases were more frequent in monogenic IBD (P<0.001). Pseudo-polyps were more common in monogenic IBD (P<0.001), while ileal edema and ulcers were significantly more common in non-monogenic IBD. IL10RA deficiency were characterized by colonic ulcers and pseudo-polyps without upper gastrointestinal tract lesions, while some patients with TNFAIP3 mutations had both upper and lower gastrointestinal tract involvement. Chronic architectural changes of crypt, increased apoptosis and eosinophils infiltration were significantly more common among non-monogenic IBD patients.

Conclusions

The endoscopy and histologic analysis of children with VEOIBD can identify features which are important to guide the diagnosis. Specific monogenic IBD can have distinct endoscopic and pathologic changes.

Objectives and Study

ESPGHAN mission is to develop evidence-based guidelines and practice recommendations in pediatric gastroenterology, hepatology, and nutrition (PGHN). The Quality of Care (QoC) Task Force of ESPGHAN aims to evaluate implementation of such standards in routine practice. Here, we present the first of these initiatives which aimed to document acquisition of anthropometric measurements in routine clinical practice.

Methods

Pediatric hospitals from 28 European countries provided pseudonymized data through online questionnaires. A baseline survey collected characteristics of hospitals and assessed standards of nutritional care, including acquisition of anthropometric measurements. Participating hospitals reviewed medical notes of eight current and eight discharged patients to retrieve additional data on anthropometric measurements and documentation in clinical routine.

Results

By 03/2023, 103 hospitals participated (68% academic, 60% certified for PGHN training, 91% with at least one pediatric gastroenterologist), thereof 10% had no nutritionist/dietician available. Lack of standard policy for weight and height assessments was reported in 17% of hospitals, no training for nursing staff performing anthropometry in 16%. A wall-mounted stadiometer to measure standing height was unavailable in 10%, equipment for sitting weight in 35%. Measuring infant length was performed in 50% of hospitals by one but not two healthcare professionals; 15% routinely used measuring tape instead of a rigid length measuring board. When we compared physician-reported estimates (0 – 100%) against collected data from patient notes on documentation of weight, height, weight percentiles, and height percentiles, physicians overestimated performance, particular regarding reporting percentiles in both, PGHN-patients (Fig. A,B) and general pediatric patients (C,D).

Conclusions

The survey identified several gaps in fundamental aspects of nutritional care of pediatric patients, including reporting of anthropometric data. The long-term QoC initiative will survey two topics per year on PGHN with re-assessment after providing educational material and feedback for benchmarking. Hospitals in Europe caring for PGHN patients are invited to join this initiative.

Objectives and Study

Late-onset neonatal meningitis (LOM) imposes high mortality and morbidity rates in preterm infants. Fecal microbiota and metabolomics are altered before late-onset sepsis (LOS) in preterm infants, suggesting that a disturbed gut colonization may be involved in LOS pathophysiology. Data on LOM are, however, lacking. The present study aimed to describe fecal microbiota and volatile metabolomics pre-LOM.

Methods

Cases and controls were selected from a prospective, longitudinal cohort study including infants born <30 weeks’ gestation at nine neonatal intensive care units. LOM was defined as a positive cerebrospinal fluid (CSF) culture or a positive blood culture with a CSF white blood cell count (WBC) >30/ul, and clinical signs of generalized infection. The microbial composition (16S rRNA sequencing) and volatile metabolome (Gas chromatography-ion mobility spectrometry (GC-IMS) and GC-time-of-flight-mass spectrometry (GC-TOF-MS)), were analyzed in fecal samples up to ten days pre-LOM.

Results

From 1397 included infants, 21 were diagnosed with LOM (1,5%). Eighteen had a positive blood culture (86%). Seven of nine positive CSF cultures contained gram-negative bacteria. Microbiota composition of 14 LOM cases from pooled samples 1-10 days pre-LOM was characterized by increased Proteobacteria abundance and decreased Bacteroidetes and Firmicutes abundance compared to matched controls. Random Forest classification on bacterial composition predicted LOM with an area under curve (AUC) of 0.88 1-3 days before clinical onset. Pattern recognition analysis of the volatile metabolome (GC-IMS) in 20 cases vs. 20 matched controls revealed an AUC of 0.70-0.76 (P<0.05) in the three days pre-LOM. GC-TOF-MS results could not identify single metabolites to differentiate between cases and controls.

Conclusions

This is the first study reporting differences in fecal microbiota, and, to a lesser extent, volatile metabolomics, between LOM and controls before clinical onset. This suggests that LOM, similarly to LOS, is highly associated with a disturbed microbial colonization, providing opportunities to develop novel therapeutic and preventive strategies.

Objectives and Study

Alagille syndrome (ALGS) is a rare autosomal dominant disorder with multi-organ involvement. Chronic cholestasis with ductopenia is commonly present, leading to pruritus and liver fibrosis. Intrahepatic bile acid (BA) retention, and increased serum BA (sBA) pool have a major role in the progression of the liver disease. Maralixibat is a minimally absorbed and selective inhibitor of the ileal bile acid transporter (IBAT) that disrupts enterohepatic BA circulation reducing the sBA pool. We present interim results of a study assessing its safety and efficacy in ALGS children with cholestasis in a real-world setting.

Methods

Patients with ALGS and compensated liver disease of 1-17 years of age weighing ≥ 5 kilograms with cholestatic pruritus and/or increased sBA concentration ≥ 2 ULN were administered with oral Maralixibat 400 µg/kg QD. Primary endpoint was sBA decrease ≥25%, secondary endpoints were pruritus (ItchRO 1-to-4 scale), frequency and severity of treatment-emergent adverse events (AEs; CTCAE v5.0).

Results

10 patients [M = 8; median age 8.5 (1-16) years] with JAG1-related ALGS were enrolled. All presented with infantile jaundice. Cardiac, vertebral, ophtalmologic, vascular, and renal involvement were present in 90%, 50%, 50%, 30%, 30%, respectively. All presented pruritus with a median ItchRO score of 2 (IQR: 1-3). After 3 months, 7 (77%) patients achieved a sBA decrease of 25% or more, while in all but one the ItchRO score improved at least by 1 point. sBA decreased from a baseline of 155 µmol/L (IQR: 31-292) to 49 µmol/L (IQR: 19.6-202) after 3 months, with a median sBA decrease of 50% (IQR: 14-62.5%). AE were grade 1 diarrhea and grade 1 abdominal pain in 2 patients each, not requiring treatment withdrawal.

Conclusions

Maralixibat is safe and effective in reducing cholestatic pruritus and sBA in children with ALGS by 3 months in a real-world cohort.

Objectives and Study

Alagille Syndrome (ALGS) is a rare genetic liver disease often responsible for severe cholestasis, intractable pruritus, and elevated serum bile acid concentration (sBA). Maralixibat is an ileal bile acid transporter (IBAT) inhibitor, available in France in the setting of an Expanded Access Program (EAP) for treatment of pruritus in ALGS patients. We report on clinical and biological data of the French cohort of ALGS patients treated with maralixibat during this EAP.

Methods

Patients were treated with maralixibat at the starting daily dose of 400 µg/kg.d, while maintaining their other antipruritic medications at constant dosage. Clinical data and biological data including sBA were prospectively collected at baseline (BL) and during the follow-up (M3, M6 then every 6 months). Pruritus was assessed by the child and or his parents using a Visual Analog Itching Scale (VAIS) graded from 0 to 10 and by the physician using a Clinical Skin Scratch Scale (CSS) graded from 0 to 4 . A clinically meaningful decrease of pruritus was defined as a ≥1 point decrease in CSS and a ≥ 3 points decrease in VAIS.

Results

15 patients with a median age of 3.6 years (range: 2.8-6.10) were included from January 2021. With treatment, mean VAIS and CSS scores decreased significantly at all time points. A non-significant decrease of means BA was observed. Mean total serum bilirubin levels remained stable throughout the study (Figure). A clinically meaningful decrease of pruritus was observed in 10/15 patients. The median duration of exposure to treatment was 12 months (range: 3-24 months). Maralixibat was definitively stopped in three patients (inefficacy, diarrhea, and non drug-related death), and transiently interrupted in one (diarrhea).

Conclusions

This real-life study confirms the efficacy of maralixibat to decrease pruritus in ALGS patients with acceptable tolerability.