Diagnosis and management of food allergy-induced constipation in young children-An EAACI position paper.

The recognition of constipation as a possible non-Immunoglobulin E (IgE)-mediated allergic condition is challenging because functional constipation (unrelated to food allergies) is a common health problem with a reported worldwide prevalence rate of up to 32.2% in children. However, many studies in children report challenge proven cow's milk allergy and constipation as a primary symptom and have found that between 28% and 78% of children improve on a cow's milk elimination diet. Due to the paucity of data and a focus on IgE-mediated allergy, not all food allergy guidelines list constipation as a symptom of food allergy. Yet, it is included in all cow's milk allergy guidelines available in English language. The Exploring Non-IgE-Mediated Allergy (ENIGMA) Task Force (TF) of the European Academy for Allergy and Clinical Immunology (EAACI) considers in this paper constipation in the context of failure of standard treatment and discuss the role of food allergens as culprit in constipation in children. This position paper used the Delphi approach in reaching consensus on both diagnosis and management, as currently published data are insufficient to support a systematic review.

An ESPGHAN Position Paper on the Diagnosis, Management, and Prevention of Cow's Milk Allergy.

A previous guideline on cow's milk allergy (CMA) developed by the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) was published in 2012. This position paper provides an update on the diagnosis, treatment, and prevention of CMA with focus on gastrointestinal manifestations. All systematic reviews and meta-analyses regarding prevalence, pathophysiology, symptoms, and diagnosis of CMA published after the previous ESPGHAN document were considered. Medline was searched from inception until May 2022 for topics that were not covered in the previous document. After reaching consensus on the manuscript, statements were formulated and voted on each of them with a score between 0 and 9. A score of ≥6 was arbitrarily considered as agreement. Available evidence on the role of dietary practice in the prevention, diagnosis, and management of CMA was updated and recommendations formulated. CMA in exclusively breastfed infants exists, but is uncommon and suffers from over-diagnosis. CMA is also over-diagnosed in formula and mixed fed infants. Changes in stool characteristics, feeding aversion, or occasional spots of blood in stool are common and in general should not be considered as diagnostic of CMA, irrespective of preceding consumption of cow's milk. Over-diagnosis of CMA occurs much more frequently than under-diagnosis; both have potentially harmful consequences. Therefore, the necessity of a challenge test after a short diagnostic elimination diet of 2-4 weeks is recommended as the cornerstone of the diagnosis. This position paper contains sections on nutrition, growth, cost, and quality of life.

Reevaluating the FDA's warning against the use of probiotics in preterm neonates: A societal statement by ESPGHAN and EFCNI.

The recent advisory issued by the United States Food and Drug Administration, cautioning against the routine administration of probiotics in preterm neonates, has sparked a lively debate within the scientific community. This commentary presents a perspective from members of the Special Interest Group on Gut Microbiota and Modifications within the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and other authors who contributed to the ESPGHAN position paper on probiotics for preterm infants, as well as representatives from the European Foundation for the Care of Newborn Infants. We advocate for a more nuanced and supportive approach to the use of certain probiotics in this vulnerable population, balancing the demonstrated benefits and risks.

Cow's Milk-related Symptom Score (CoMiSS) values in presumed healthy European infants aged 6-12 months: a cross-sectional study.

The Cow's Milk-related Symptom Score (CoMiSS) is an awareness tool for evaluating cow's milk-related symptoms. Previous studies have focused on providing CoMiSS values for healthy and symptomatic infants aged 0-6 months. However, there is a notable gap in the literature concerning CoMiSS values for infants older than 6 months. This cross-sectional study aimed to determine CoMiSS values in presumed healthy infants who have completed 6 months and are up to 12 months old, hereafter referred to as 6 to 12 months old. Physicians from six European countries prospectively determined CoMiSS values in infants attending well-child clinics. Exclusion criteria included preterm delivery, acute or chronic disease, and the consumption of a therapeutic formula, dietary supplements (except vitamins), or medication. The following information was collected: gestational age, gender, age, type of feed (breast milk or infant formula), and complementary feeding. Descriptive statistics were summarized with mean and standard deviation for normally distributed continuous variables, median and IQR for non-normally distributed variables, and differences in CoMiSS values were analyzed with appropriate tests. Data from 609 infants were obtained. The overall median (Q1-Q3) CoMiSS values were 3 (1-5). Significant differences were found across age groups (p < 0.001), but not across groups based on gender (p = 0.551) or feeding type (p = 0.880).   Conclusions: This study provided CoMiSS values in presumed healthy infants aged 6-12 months. Additional studies should be conducted to establish the use of CoMiSS to assess cow's milk-related symptoms in infants 6 months and older. What is Known: • The Cow's Milk-related Symptom Score (CoMiSS) is an awareness tool for evaluating symptoms related to cow's milk. • CoMiSS values for presumed healthy infants aged 0-6 months infants are already available. What is New: • CoMiSS values in European infants aged 6-12 months are provided. • These CoMiSS values differed across various age groups but not across groups based on gender or feeding type.

Infant gastroesophageal reflux disease management consensus.

AIM: Infant gastroesophageal reflux is mostly benign; however, when associated with complications like failure to thrive, it may be indicative of gastroesophageal reflux disease. There are currently several unmet needs pertaining to the management of infant gastroesophageal reflux (disease). Reflux in infants is mostly composed of breast milk or formula, so this population is significantly different to older children and adults. The objective of this Delphi consensus was to establish recommendations based on published literature and the experience of clinical experts in paediatric gastroenterology in the context of infant gastroesophageal reflux (disease). METHODS: The Delphi methodology was used to obtain a consensus on 18 statements relating to clinical aspects of infant gastroesophageal reflux (disease). RESULTS: The expert panel comprising paediatric gastroenterology clinical specialists reached a consensus for all statements by means of an online, anonymised voting system. CONCLUSION: It was highlighted that there is generally low awareness of or adherence to guidelines in clinical practice and that acid suppression therapy should not be indicated for non-acid reflux, which constitutes a significant proportion of total gastroesophageal reflux episodes among infants. Furthermore, it was emphasised that there is an unmet medical need for therapy for some symptomatic infants with non-acid reflux disease.

How Best to Estimate Insertion Length of Multichannel Intraluminal Impedance pH Probes in Children.

OBJECTIVE: To assess the reliability of the KidZ Health Castle formula (KHC-F) to determine the correct probe position of a multichannel intraluminal impedance pH. STUDY DESIGN: A retrospective cohort study was performed on 222 children between 1 month and 18 years of age undergoing multichannel intraluminal impedance pH. The primary outcome was the comparison of the pH sensor location determined by the KHC-F with the radiological target position. The margin of error was defined as 1 cm from the target position. Performance of the KHC-F and existing formulas was determined via the percentage with a correct position, mean error, 95% limits of agreement (Bland-Altman plots), and Spearman correlation. A post hoc analysis was performed with an updated KHC-F v2, subtracting -0.5 cm from the KHC-F. RESULTS: Positioning with KHC-F was correct in two-thirds of the participants, with a very strong correlation (ρ = 0.91) with the target position. Bland-Altman plots showed good agreement between KHC-F and target position (mean error of -0.44 cm, lower limit -3.2 cm, upper limit 2.3 cm). A post hoc analysis with the KHC-F v2 showed a correct positioning in 74% of patients. Comparison with other formulas showed a stronger performance of KHC-F and KHC-F v2 on correct positioning, mean error, and 95% limits of agreement. CONCLUSIONS: The KHC-F leads to reliable results. KHC-F v2 outperforms all other existing formulas in children, thereby reducing the need for repositioning and the amount of x-ray exposure. The age distribution of the sample may be a limitation, as well as the retrospective nature of the study.

The role of online symptom questionnaires to support the diagnosis of cow's milk allergy in children for healthcare professionals - A Delphi consensus study.

BACKGROUND: Cow's milk allergy (CMA) is one of the most common food allergies world-wide. The emergence of online CMA symptom questionnaires, aimed at parents and/or healthcare professionals (HCP), may raise awareness about the possible diagnosis of CMA, but also increases the risk for overdiagnosis leading to unnecessary dietary restriction impacting on growth and nutrition. This publication sets out to establish the availability of these CMA symptom questionnaires and critically assesses the development and validity. METHODS: Thirteen HCP working in the field of CMA, from different countries, were recruited to participate. A combination of a Pubmed and CINAHL literature and online review using the Google search engine in English language was used. Symptoms in the questionnaires were assessed, using the European Academy for Allergy and Clinical Immunology guidelines for food allergy. Following the assessment of both the questionnaires and literature, the authors followed the modified Delphi approach to generate consensus statements. RESULTS: Six hundred and fifty-one publications were identified, of which 29 were suitable for inclusion, with 26 being associated with the Cow's Milk-Related Symptoms Score. The online search yielded 10 available questionnaires: 7/10 were sponsored by formula milk companies and 7/10 were aimed at parents and three at HCP. Following the assessment of data, 19 statements were generated in two rounds of anonymous voting reaching 100% agreement. CONCLUSIONS: Online CMA questionnaires, available to parents and HCP's, are varied in symptoms, and most were not validated. The overarching consensus generated from authors is that these questionnaires should not be used without the involvement of HCP.

Synbiotics in the Management of Pediatric Gastrointestinal Disorders: Position Paper of the ESPGHAN Special Interest Group on Gut Microbiota and Modifications.

BACKGROUND: 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. AIM: The purpose of this article is to provide recommendations for the use of synbiotics in the management of pediatric gastrointestinal disorders. The recommendations are developed by the ESPGHAN Special Interest Group on Gut Microbiota and Modifications. METHODS: From existing literature databases, we searched and appraised all systematic reviews and/or meta-analyses, and subsequently published randomized controlled trials (RCTs) that compared the use of synbiotics, in all delivery vehicles and formulations, at any dose, compared to no synbiotics. Synbiotics which are part of infant formula were not assessed. The recommendations were formulated only if at least 2 RCTs that used a well-defined synbiotic were available. RESULTS: Based on the currently available evidence, no recommendation can be formulated in favor or against the use of evaluated synbiotic combination in the treatment of acute gastroenteritis, prevention of necrotizing enterocolitis, Helicobacter pylori infection, inflammatory bowel disease, functional gastrointestinal disorders, and allergy in infants and children. CONCLUSIONS: There is a need for more, well-designed RCTs on the role of synbiotics in gastrointestinal disorders with the same outcome measures to enable the inter-studies comparisons.

Cow's Milk-Related Symptom Score (CoMiSS): From Bristol to Brussels Stool Scale.

OBJECTIVES: The Cow's Milk-related Symptom Score (CoMISS) is an awareness tool for evaluating cow's milk-related symptoms in otherwise healthy infants <1 year of age. This study assessed whether replacing the Bristol Stool Form Scale (BSFS) with the Brussels Infants and Toddlers Stool Scale (BITSS) in non-toilet-trained infants would modify the overall CoMiSS and change the clinical approach regarding potential cow's milk allergy. METHODS: Non-toilet-trained infants aged <13 months were assessed by CoMiSS using the 7 images from the BSFS (CoMiSS-BSFS) compared to the 4 images of stools from BITSS (CoMiSS-BITSS). The Wilcoxon signed-rank test and Pearson correlation coefficient were calculated. A post hoc analysis using identical tests was performed in subsets of CoMiSS-BSFS scores ≥10, ≥12, ≤5, and ≥6. RESULTS: Eight hundred forty-four pairwise scores were collected. Applying the Wilcoxon test over the complete dataset, the difference between CoMiSS-BSFS and CoMiSS-BITSS was statistically significant ( P < 0.001). However, there was no significant difference in the subsets with CoMiSS-BSFS ≥10, ≥12, and ≥6 ( P = 0.84, P = 0.48, and P = 0.81, respectively). The significant difference remained restricted to the group with CoMiSS-BSFS ≤5, considered at low risk for CM-related symptoms ( P < 0.001). CONCLUSION: Replacing BSFS with BITSS does not change the cutoff for awareness of possible CM-related symptoms and will not impact the use of CoMiSS in clinical practice. Changes in CoMiSS remained limited to the subgroup with a low risk for CM-related symptoms.

An ESPGHAN position paper on the diagnosis, management and prevention of cow's milk allergy.

A previous guideline on cow's milk allergy (CMA) developed by the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) was published in 2012. This position paper provides an update on the diagnosis, treatment, and prevention of CMA with focus on gastrointestinal manifestations. All systematic reviews and meta-analyses regarding prevalence, pathophysiology, symptoms, and diagnosis of CMA published after the previous ESPGHAN document were considered. Medline was searched from inception until May 2022 for topics that were not covered in the previous document. After reaching consensus on the manuscript, statements were formulated and voted on each of them with a score between 1 and 9. A score of ≥6 was arbitrarily considered as agreement. Available evidence on the role of dietary practice in the prevention, diagnosis and management of CMA was updated and recommendations formulated. CMA in exclusively breastfed infants exists, but is uncommon and suffers from over-diagnosis. CMA is also over-diagnosed in formula and mixed fed infants. Changes in stool characteristics, feeding aversion or occasional spots of blood in stool are common and in general should not be considered as diagnostic of CMA, irrespective of preceding consumption of cow's milk. Over-diagnosis of CMA occurs much more frequently than under-diagnosis; both have potentially harmful consequences. Therefore, the necessity of a challenge test after a short diagnostic elimination diet of 2-4 weeks is recommended as the cornerstone of the diagnosis. This position paper contains sections on nutrition, growth, cost and quality of life.

Probiotics for the Management of Pediatric Gastrointestinal Disorders: Position Paper of the ESPGHAN Special Interest Group on Gut Microbiota and Modifications.

BACKGROUND: Probiotics, defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host, are widely used despite uncertainty regarding their efficacy and discordant recommendations about their use. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Special Interest Group on Gut Microbiota and Modifications provides updated recommendations for the use of probiotics for the management of selected pediatric gastrointestinal disorders. METHODS: All systematic reviews and/or meta-analyses, as well as subsequently published randomized controlled trials (RCTs) (until December 2021), that compared the use of probiotics in all delivery vehicles and formulations, at any dose, with no probiotic (ie, placebo or no treatment), were eligible for inclusion. The recommendations were formulated only if at least 2 RCTs on a similar well-defined probiotic strain were available. The modified Delphi process was used to establish consensus on the recommendations. RESULTS: Recommendations for the use of specific probiotic strains were made for the management of acute gastroenteritis, prevention of antibiotic-associated diarrhea, nosocomial diarrhea and necrotizing enterocolitis, management of Helicobacter pylori infection, and management of functional abdominal pain disorders and infant colic. CONCLUSIONS: Despite evidence to support the use of specific probiotics in some clinical situations, further studies confirming the effect(s) and defining the type, dose, and timing of probiotics are still often required. The use of probiotics with no documented health benefits should be discouraged.

Generation and application of a convolutional neural networks algorithm in evaluating stool consistency in diapers.

AIM: The aim of the study was to develop a deep convolutional neural networks (CNNs) algorithm for automated assessment of stool consistency from diaper photographs and test its performance under real-world conditions. METHODS: Diaper photographs were enrolled via a mobile phone application. The stool consistency was assessed independently according to the Brussels Infant and Toddler Stool Scale (BITSS) by paediatricians. These images were randomised into a training data set and a test data set. After training and testing, the new algorithm was used under real-world conditions by parents. RESULTS: There was an overall agreement of 92.9% between paediatricians and the CNN-generated algorithm. Post hoc classification into the validated 4 categories of the BITSS yielded an agreement of 95.4%. Spearman correlation analysis across the ranking of 7 BITSS photographs and validated 4 categories showed a significant correlation of rho = 0.93 (95% CI, 0.92, 0.94; p < 0.001) and rho = 0.92 (95% CI, 0.90, 0.93; p < 0.001), respectively. The real-world application yielded further insights into changes in stool consistency between age categories and mode of feeding. CONCLUSION: The new CNN-based algorithm is able to reliably identify stool consistency from diaper photographs and may support the communication between parents and paediatricians.

Development of a Core Outcome Set for Children Aged 1-18 Years with Gastroesophageal Reflux Disease.

OBJECTIVE: To develop a core outcome set for clinical studies assessing gastroesophageal reflux disease (GERD) in children. STUDY DESIGN: This core outcome set was developed using a 2-round Delphi technique and adhering to the Outcome Measures in Rheumatology Initiative (OMERACT 2.0) recommendations. Healthcare professionals (HCPs) and (parents of) children (age 1-18 years) with a GERD diagnosis (ie, the presence of bothersome symptoms), listed up to 5 harmful and/or beneficial outcomes that they considered important in the treatment of GERD. Outcomes mentioned by more than 10% of participants were put forward and rated and prioritized by HCPs, parents, and children in a second round. Outcomes with the highest rank formed the draft core outcome set. The final core outcome set was created during an online consensus meeting between an expert panel. RESULTS: The first round was completed by 118 of 125 HCPs (94%), 146 of 146 parents (100%), and 69 of 70 children (99%). A total of 80 of 118 HCPs (68%), 130 of 140 parents (93%), and 77 children (100%) completed round 2. "Adequate relief," "evidence of esophagitis," "feeding difficulties," "heartburn (≥4 years)," "hematemesis," "regurgitation," "sleeping difficulties," "vomiting," and "adverse events" were included in the final core outcome set for GERD in children aged 1-18 years. CONCLUSIONS: We identified a total set of 9 core outcomes and suggest these outcomes to be minimally measured in clinical studies assessing GERD in children. Implementation of this core outcome set is likely to increase comparison between studies and may thus provide future recommendations to improve treatment of GERD in children.

Diagnosis and management of food allergy-associated gastroesophageal reflux disease in young children-EAACI position paper.

Gastro-oesophageal reflux (GOR) and food allergy (FA) are common conditions, especially during the first 12 months of life. When GOR leads to troublesome symptoms, that affect the daily functioning of the infant and family, it is referred to as GOR disease (GORD). The role of food allergens as a cause of GORD remains controversial. This European Academy of Allergy and Clinical Immunology (EAACI) position paper aims to review the evidence for FA-associated GORD in young children and translate this into clinical practice that guides healthcare professionals through the diagnosis of suspected FA-associated GORD and medical and dietary management. The task force (TF) on non-IgE mediated allergy consists of EAACI experts in paediatric gastroenterology, allergy, dietetics and psychology from Europe, United Kingdom, United States, Turkey and Brazil. Six clinical questions were formulated, amended and approved by the TF to guide this publication. A systematic literature search using PubMed, Cochrane and EMBASE databases (until June 2021) using predefined inclusion criteria based on the 6 questions was used. The TF also gained access to the database from the European Society of Paediatric Gastroenterology and Hepatology working group, who published guidelines on GORD and ensured that all publications used within that position paper were included. For each of the 6 questions, practice points were formulated, followed by a modified Delphi method consisting of anonymous web-based voting that was repeated with modified practice points where required, until at least 80% consensus for each practice point was achieved. This TF position paper shares the process, the discussion and consensus on all practice points on FA-associated GORD.

Efficacy and safety of medical and nutritional management of gastroesophageal reflux in formula-fed infants: a narrative review.

PURPOSE OF REVIEW: The prescription of proton pump inhibitors has an increasing trend, despite that guidelines recommend nutritional management as first-line management. A thickened antiregurgitation formula is recommended in formula-fed infants. In this review we focus on the novel insights in management of formula-fed infants with gastroesophageal reflux disease (GERD). RECENT FINDINGS: New data are limited. Concerning thickened antiregurgitation formula, locust bean gum has been the most studied and has limited adverse effects. However, positive results were also obtained with pectin. The effect of pro- and prebiotics on regurgitation is unclear. The overlap between cow's milk allergy and gastroesophageal reflux remains a challenge. SUMMARY: Very limited new data were published during the last 18 months. Thickened antiregurgitation formula is the first-line approach in formula-fed infants with GERD. No specific thickening agent can be recommended because of lack of comparative trials. Proton pump inhibitors are over prescribed in infants.

Colonic Function Investigations in Children: Review by the ESPGHAN Motility Working Group.

ABSTRACT: Disorders of colonic motility, most often presenting as constipation, comprise one of the commonest causes of outpatient visits in pediatric gastroenterology. This review, discussed and created by the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Motility Working Group, is a practical guide, which highlights the recent advances in pediatric colonic motility testing including indications, technical principles of the tests, patient preparation, performance and basis of the results' analysis of the tests. classical methods, such as colonic transit time (cTT) with radiopaque markers and colonic scintigraphy, as well as manometry and novel techniques, such as wireless motility capsule and electromagnetic capsule tracking systems are discussed.

Anorectal Manometry in Children: The Update on the Indications and the Protocol of the Procedure.

ABSTRACT: Anorectal disorders are common in children. They are related to structural and/or functional abnormalities of the anorectum or pelvic floor with a variety of symptoms. Therefore, diagnostic tests to evaluate anorectal function can help to better understand the underlying pathophysiology and aetiology as well as facilitate patient management. During the past decades, substantial efforts have been made to improve anorectal function testing; however, more advanced investigations might lead to difficulties in interpretation. Additionally, a great diversity of equipment and protocols are used among centres, which may lead to heterogeneous interpretation of results. More studies to standardize methods of testing and validate reference values are strongly recommended in children. This review updates on the current indications and the protocol of anorectal manometry.

Intra-rater Variability of the Brussels Infants and Toddlers Stool Scale (BITSS) Using Photographed Stools.

OBJECTIVES: The Brussels Infants and Toddlers Stool Scale (BITSS) was developed for the assessment of stool consistency in non-toilet-trained children. This study aimed to (1) investigate the intra-rater reliability of the BITSS among health care professionals (HCPs) and caregivers (CGs); (2) study a potential learning curve; (3) explore the impact of photo quality on intra-rater reliability. METHODS: Photos of diapers containing stool were assessed twice by 4 HCP (2432 photos) and 8 CGs (492 photos) using the BITTS. Intra-rater reliability was calculated by the percentage of exact agreement and a κ-value. A learning effect and the impact of photo quality was explored using mixed linear model and generalized estimating equations. RESULTS: HCPs generated 24,320 stool consistency ratings: 12.1% were scored as watery, 31.0% loose, 29.4% formed, and 27.6% hard. CGs performed 7872 ratings: 9.2% classified as watery, 34.6% loose, 28.9% formed, and 27.3% hard. Intra-rater reliability (κ) for HCPs ranged from 0.64 [95% confidence interval (CI) = 0.61-0.66] to 0.78 (95% CI = 0.76-0.80) and from 0.68 (95% CI = 0.63-0.73) to 0.94 (95% CI = 0.91-0.97) in the CG group. Both groups had <1% improvement in the odds of identical classification per 50 photos. The percentage of absolute agreement was higher in photos rated as good quality than those that were not (HCPs: 80.3% vs 69.5%, P < 0.001; CGs: 90.4% vs 86.3%, P < 0.001). CONCLUSIONS: The BITSS has an excellent intra-rater reliability for the stool consistency scoring of photographs of stools in diapers, but can be influenced by photo quality. A clinically meaningless learning effect was found.

Are pro- and/or synbiotics beneficial in Helicobacter pylori eradication therapy in children? A narrative review.

To assess the effect of pro- and synbiotics in the eradication therapy of Helicobacter pylori (Hp), as well as their effect on adverse effects and therapy compliance in children, a review was performed. We searched for relevant studies published in the English language in PubMed in the last 5 years. Articles were extracted using subject heading and keywords of interest to the topic. There is low-quality evidence that Lactobacillus casei, Bifidobacterium infantis, and Clostridium butyricum (only one RCT for all three) and Saccharomyces boulardii (more than 1 RCT) increase the eradication rate and decrease the adverse effects. Data with synbiotics report only a trend towards a better eradication. Heterogeneity in study designs and outcomes is a major limitation to propose evidence-based recommendations. A reduced incidence of antibiotic-associated diarrhoea is reported. Therapy compliance has been poorly studied.   Conclusion: Due to study heterogeneity, there is very low evidence that some specific probiotics strains increase the eradication rate of Hp when added to standard eradication therapy in children. Whether this is related to immunological effects of the strain or a decrease of adverse effects is not known. More studies, especially comparative trials, are needed before the addition of pro- or synbiotics to Hp eradication treatment can be recommended in daily routine. What is Known: • Eradication treatment of Helicobacter pylori in children has a low success rate and induces frequently adverse effects. • The addition of probiotics might improve eradication and decrease adverse effects, but no paediatric guideline does recommend probiotics as part of the eradication treatment. What is New: • There is low-quality evidence that Lactobacillus casei, Bifidobacteria infantis, and Clostridium butyricum (only one randomized controlled trial (RCT) for all three) and Saccharomyces boulardii (more than 1 RCT) increase the eradication rate and decrease the adverse effects. • Data with synbiotics report only a trend towards a better eradication.

Intestinal microbiota composition of children with infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and multisystem inflammatory syndrome (MIS-C).

Microbiota composition may play a role in the development, prognosis, or post-infection of COVID-19. There are studies evaluating the microbiota composition at the time of diagnosis and during the course of COVID-19, especially in adults, while studies in children are limited and no study available in children with multisystem inflammatory syndrome in children (MIS-C). This study was planned to compare intestinal microbiota composition in children diagnosed with MIS-C and acute COVID-19 infection with healthy children. In this prospective multicenter study, 25 children diagnosed with MIS-C, 20 with COVID-19 infection, and 19 healthy children were included. Intestinal microbiota composition was evaluated by 16 s rRNA gene sequencing. We observed changes of diversity, richness, and composition of intestinal microbiota in MIS-C cases compared to COVID-19 cases and in the healthy controls. The Shannon index was higher in the MIS-C group than the healthy controls (p < 0.01). At phylum level, in the MIS-C group, a significantly higher relative abundance of Bacteroidetes and lower abundance of Firmicutes was found compared to the control group. Intestinal microbiota composition changed in MIS-C cases compared to COVID-19 and healthy controls, and Faecalibacterium prausnitzii decreased; Bacteroides uniformis, Bacteroides plebeius, Clostridium ramosum, Eubacterium dolichum, Eggerthella lenta, Bacillus thermoamylovorans, Prevotella tannerae, and Bacteroides coprophilus were dominant in children with MIS-C. At species level, we observed decreased Faecalibacterium prausnitzii, and increased Eubacterium dolichum, Eggerthella lenta, and Bacillus thermoamylovorans in children with MIS-C and increased Bifidobacterium adolescentis and Dorea formicigenerasus in the COVID-19 group. Our study is the first to evaluate the microbiota composition in MIS-C cases. There is a substantial change in the composition of the gut microbiota: (1) reduction of F. prausnitzii in children with MIS-C and COVID-19; (2) an increase of Eggerthella lenta which is related with autoimmunity; and (3) the predominance of E. dolichum is associated with metabolic dysfunctions and obesity in children with MIS-C. CONCLUSIONS:  Alterations of the intestinal microbiota might be part of pathogenesis of predisposing factor for MIS-C. It would be beneficial to conduct more extensive studies on the cause-effect relationship of these changes in microbiota composition and their effects on long-term prognosis. WHAT IS KNOWN: • Microbiota composition may play a role in the development, prognosis, or post-infection of COVID-19.  • However, the number of studies on children is limited, and no study on multisystem inflammatory syndrome in children is currently available (MIS-C). WHAT IS NEW: • In individuals with MIS-C, the composition of the gut microbiota changed dramatically. • Decreased Faecalibacterium prausnitzii have been observed, increased Eggerthella lenta, which was previously linked to autoimmunity, and predominance of Eubacterium dolichum which was linked to metabolic dysfunction and obesity.