Gut Microbiota Composition In Children Research Articles

Alterations in gut microbiota and metabolite profiles in patients with infantile cholestasis

BackgroundInfantile cholestasis (IC) is the most common hepatobiliary disease in infants, resulting in elevated direct bilirubin levels. Indeed, hepatointestinal circulation impacts bile acid and bilirubin metabolism. This study evaluates changes in the gut microbiota composition in children with IC and identifies abnormal metabolite profiles associated with microbial alterations.ResultsThe gut microbiota in the IC group exhibits the higher abundance of Veillonella, Streptococcus and Clostridium spp. (P < 0.05), compared to healthy infants (CON) group. Moreover, the abundance of Ruminococcus, Vibrio butyricum, Eubacterium coprostanogenes group, Intestinibacter, and Faecalibacterium were lower (P < 0.05). In terms of microbiota-derived metabolites, the levels of fatty acids (palmitoleic, α-linolenic, arachidonic, and linoleic) (P < 0.05) increased and the levels of amino acids decreased in IC group. Furthermore, the abundances of Ruminococcus, Eubacterium coprostanoligenes group, Intestinibacter and Butyrivibrio are positively correlated with proline, asparagine and aspartic acid, but negatively correlated with the α-linolenic acid, linoleic acid, palmitoleic acid and arachidonic acid. For analysis of the relationship between the microbiota and clinical index, it was found that the abundance of Veillonella and Streptococcus was positively correlated with serum bile acid content (P < 0.05), while APTT, PT and INR were negatively correlated with Faecalibalum and Ruminococcus (P < 0.05).ConclusionMicrobiota dysbiosis happened in IC children, which also can lead to the abnormal metabolism, thus obstructing the absorption of enteral nutrition and aggravating liver cell damage. Veillonella, Ruminococcus and Butyrivibrio may be important microbiome related with IC and need further research.

Children and adolescents with attention deficit hyperactivity disorder and autism spectrum disorder share distinct microbiota compositions

ABSTRACT An association has been suggested between altered gut microbiota, and attention deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD), respectively. Thus, we analyzed the gut microbiota composition in children and adolescents with or without these disorders and evaluated the systemic effects of these bacteria. We recruited study participants diagnosed with ADHD, ASD, and comorbid ADHD/ASD, while the control groups consisted both of siblings and non-related children. The gut microbiota was analyzed by 16S rRNA gene sequencing of the V4 region, while the concentration of lipopolysaccharide-binding protein (LBP), cytokines, and other signaling molecules were measured in plasma. Importantly the gut microbiota compositions of cases with ADHD and ASD were highly similar for both alpha- and beta-diversity while differing from that of non-related controls. Furthermore, a subset of ADHD and ASD cases had an increased LBP concentration compared to non-affected children, which was positively correlated with interleukin (IL)-8, 12, and 13. These observations indicate disruption of the intestinal barrier and immune dysregulation among the subset of children with ADHD or ASD.

In children with cow's milk allergy, 1-kestose affects the gut microbiota and reaction threshold.

Interventions targeting the gut microbiota for treating food allergy (FA) have been gaining much attention. Although several studies have examined the effects of probiotics, few have verified the effects of prebiotic intervention on FA in humans. We conducted a preliminary open-label, parallel-group comparison trial in children diagnosed with severe cow's milk allergy (CMA) who were instructed to ingest baked milk (BM; bread or cookies) daily. The subjects either received or did not receive the prebiotic 1-kestose (kestose) daily for 6 months. CMA symptoms and the threshold dose for milk protein were evaluated by oral food challenge with heated milk or BM. Blood and fecal samples were also collected for investigations of the antigen-specific immunoglobulin (Ig) E levels and microbiota composition. Kestose treatment significantly increased the threshold dose for milk protein, and decreased the milk- and casein-specific IgE levels in serum. In those treated with kestose, the abundance of Fusicatenibacter spp. significantly increased in the feces, and a significant inverse correlation was seen between the abundance of Fusicatenibacter spp. and the milk- and casein-specific IgE levels. Kestose treatment induced some tolerance to milk protein via changes in the gut microbiota composition in children with FA. A 6-month treatment with the prebiotic kestose increased the threshold dose for milk protein, and decreased the serum levels of milk- and casein-specific IgE in children diagnosed with cow's milk allergy. The kestose treatment increased the abundance of Fusicatenibacter spp. in the gut, which was inversely correlated with the antigen-specific IgE levels. This is the first study to demonstrate that a prebiotic intervention induced some tolerance to an allergen in children with food allergy.

Altered gut microbiota composition in children and their caregivers infected with the SARS-CoV-2 Omicron variant.

Gut microbiota alterations have been implicated in the pathogenesis of coronavirus disease 2019 (COVID-19). This study aimed to explore gut microbiota changes in a prospective cohort of COVID-19 children and their asymptomatic caregivers infected with the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) Omicron variant. A total of 186 participants, including 59 COVID-19 children, 50 asymptomatic adult caregivers, 52 healthy children (HC), and 25 healthy adults (HA), were recruited between 15 April and 31 May 2022. The gut microbiota composition was determined by 16S rRNA gene sequencing in fecal samples collected from the participants. Gut microbiota functional profiling was performed by using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) software. The gut microbiota analysis of beta diversity revealed that the fecal microbial community of COVID-19 children remained far distantly related to HC. The relative abundances of the phyla Actinobacteria and Firmicutes were decreased, whereas Bacteroidetes, Proteobacteria, and Verrucomicrobiota were increased in COVID-19 children. Feces from COVID-19 children exhibited notably lower abundances of the genera Blautia, Bifidobacterium, Fusicatenibacter, Streptococcus, and Romboutsia and higher abundances of the genera Prevotella, Lachnoclostridium, Escherichia-Shigella, and Bacteroides than those from HC. The enterotype distributions of COVID-19 children were characterized by a high prevalence of enterotype Bacteroides. Similar changes in gut microbiota compositions were observed in asymptomatic caregivers. Furthermore, the microbial metabolic activities of KEGG (Kyoto Encyclopedia of Genes and Genomes) and COG (cluster of orthologous groups of proteins) pathways were perturbed in feces from subjects infected with the SARS-CoV-2 Omicron variant. Our data reveal altered gut microbiota compositions in both COVID-19 children and their asymptomatic caregivers infected with the SARS-CoV-2 Omicron variant, which further implicates the critical role of gut microbiota in COVID-19 pathogenesis.

The Therapeutic Role of Short-Chain Fatty Acids Mediated Very Low-Calorie Ketogenic Diet-Gut Microbiota Relationships in Paediatric Inflammatory Bowel Diseases.

The very low-calorie ketogenic diet (VLCKD) has been recognized as a promising dietary regimen for the treatment of several diseases. Short-chain fatty acids (SCFAs) produced by anaerobic bacterial fermentation of indigestible dietary fibre in the gut have potential value for their underlying epigenetic role in the treatment of obesity and asthma-related inflammation through mediating the relationships between VLCKD and the infant gut microbiota. However, it is still unclear how VLCKD might influence gut microbiota composition in children, and how SCFAs could play a role in the treatment of inflammatory bowel disease (IBD). To overcome this knowledge gap, this review aims to investigate the role of SCFAs as key epigenetic metabolites that mediate VLCKD–gut microbiota relationships in children, and their therapeutic potential in IBD.

Gut Microbiome Suffers from Hematopoietic Stem Cell Transplantation in Childhood and Its Characteristics Are Positively Associated with Intra-Hospital Physical Exercise.

Simple SummaryGut microbiome research has rapidly advanced with good perspectives for the diagnostics and/or therapy of a plethora of diseases, including metabolic and neurodegenerative diseases and various types of cancer. In this study, we examined the composition of the fecal microbiota of eligible children with acute lymphoblastic leukemia (ALL) after hematopoietic stem cell transplantation (HSCT). We found a negative effect of HSCT treatment on microbiome bacterial diversity and richness with microbial monodominance by pathogenic bacteria in pediatric ALL patients after 3 months. The changes in the gut microbiota were associated with systemic inflammation on day + 28. However, promisingly, we have observed an association between bacterial diversity and physical exercise during HSCT treatment. Our findings provide additional support for the importance of investigating the gut microbiome in children with cancer.Gut microbiome impairment is a serious side effect of cancer treatment. The aim of this study was to identify the effects of hematopoietic stem cell transplantation (HSCT) treatment on gut microbiota composition in children with acute lymphoblastic leukemia (ALL). Fecal microbiotas were categorized using specific primers targeting the V1–V3 region of 16S rDNA in eligible pediatric ALL patients after HSCT (n = 16) and in healthy controls (Ctrl, n = 13). An intra-hospital exercise program was also organized for child patients during HSCT treatment. Significant differences in gut microbiota composition were observed between ALL HSCT and Ctrl with further negative effects. Plasma C-reactive protein correlated positively with the pathogenic bacteria Enterococcus spp. and negatively with beneficial bacteria Butyriccocus spp. or Akkermansia spp., respectively (rs = 0.511, p = 0.05; rs = −0.541, p = 0.04; rs = −0.738, p = 0.02). Bacterial alpha diversity correlated with the exercise training characteristics. Therefore, specific changes in the microbiota of children were associated with systemic inflammation or the ability to exercise physically during HSCT treatment.

Gut-Lung Axis: Microbial Crosstalk in Pediatric Respiratory Tract Infections.

The gut microbiota is an important regulator for maintaining the organ microenvironment through effects on the gut-vital organs axis. Respiratory tract infections are one of the most widespread and harmful diseases, especially in the last 2 years. Many lines of evidence indicate that the gut microbiota and its metabolites can be considered in therapeutic strategies to effectively prevent and treat respiratory diseases. However, due to the different gut microbiota composition in children compared to adults and the dynamic development of the immature immune system, studies on the interaction between children’s intestinal flora and respiratory infections are still lacking. Here, we describe the changes in the gut microbiota of children with respiratory tract infections and explain the relationship between the microbiota of children with their immune function and disease development. In addition, we will provide perspectives on the direct manipulation of intestinal microbes to prevent or treat pediatric respiratory infections.

Gut microbiota composition in children with obstructive sleep apnoea syndrome: a pilot study

BackgroundObstructive Sleep Apnoea syndrome (OSAS) is considered a systemic inflammatory disease and is characterized by intermittent hypoxia that can damage the integrity of intestinal barrier and alter gut microbiota composition in adults and animal models. To date there is only one study on snoring children and microbiota but no studies are present on paediatric OSAS related dysbiosis. Study objectivesTo evaluate gut microbiota composition in OSAS children in respect to healthy subjects and investigate the role of sleep parameters in changing gut microbiome. MethodsSixteen children divided in OSAS and healthy groups. Stool samples were collected from both the two groups to assess gut microbiota composition using 16S rRNA sequencing and a nocturnal pulsossimetry and polysomnography were performed in OSAS children. ResultsOSAS children showed a decreased microbial diversity in respect to healthy subjects in terms of number of observed species and Chao1 index (p = 0,01). Firmicutes/Bacteroidetes ratio was directly correlated to Sleep Clinical Record (p = 0,03). The abundance of several inflammation-related strains (Proteobacteria, Clostridiaceae, Oscillospiraceae, Klebsiella) were found significantly modified in relation to sleep parameters. Bacteria implied in the gut barrier integrity (Desulfovibrionaceae, Bacteroides fragilis and Faecalibacterium prausnitzii) were found significantly different in the two study groups and correlated with sleep parameters. ConclusionsOSAS children showed a lower microbiota diversity in respect to heathy subjects and an increase of inflammation and gut barrier disruptors-related strains probably induced by intermittent hypoxia. Further studies should be conducted to understand the role of gut microbiota in OSAS physiopathology and comorbidities in children.

Alterations in Gut Glutamate Metabolism Associated with Changes in Gut Microbiota Composition in Children with Autism Spectrum Disorder.

Changes in the gut microenvironment may influence the pathogenesis of autism spectrum disorders (ASD). Here, we investigated the composition of the gut microbiota and metabolites in children with ASD. Ninety-two children with ASD and 42 age-matched children exhibiting typical development (TD) were enrolled in the two-stage study. In the discovery stage, shotgun metagenomic sequencing and liquid chromatography-mass spectrometry (LC-MS) were performed simultaneously on fecal samples obtained from 43 children in the ASD group and 31 children in the TD group. Systematic bioinformatic analyses were performed to identify gut metabolites associated with altered gut microbiota composition. At the validation stage, differential metabolites were tested using LC-MS with an additional 49 and 11 children in the ASD and TD groups, respectively. Altered glutamate metabolites were found in the ASD group, along with a decline in 2-keto-glutaramic acid and an abundance of microbiota associated with glutamate metabolism. These changes in glutamate metabolism were correlated with lower levels of the highly abundant bacteria Bacteroides vulgatus and higher levels of the potentially harmful Eggerthella lenta and Clostridium botulinum. Lower gut cortisol levels have also been identified in the ASD group and associated with changes in gut microbiota glutamate metabolism. Finally, gut 2-keto-glutaramic acid was validated as a potential biomarker for ASD. The significant changes in the gut microenvironment in children with ASD may provide new insight into the cause of ASD and aid in the search for diagnostic and therapeutic approaches. IMPORTANCE Multiple lines of evidence suggest that the gut microbiota may play an important role in the pathogenesis of ASD, but the specific mechanism is still unclear. Through a comprehensive gut metagenomic and metabolome study of children with ASD, alterations in gut metabolite composition were found in children with ASD, and these alterations were linked to changes in gut microbiota composition. This may give us a deeper understanding of the role of gut microbiota in the pathogenesis of ASD.

Mixed Viral-Bacterial Infections and Their Effects on Gut Microbiota and Clinical Illnesses in Children

Acute gastroenteritis remains a major cause of morbidity and mortality among young children worldwide. It accounts for approximately 1.34 million deaths annually in children younger than five years. Infection can be caused by viral, bacterial and/or parasitic microorganisms. Dysbiosis due to such infections could dramatically affect disease prognosis as well as development of chronic illness. The aim of this study was to analyze gut microbiome and clinical outcomes in young children suffering from viral or mixed viral-bacterial infection. We evaluated gut microbiota composition in children suffering from viral or mixed viral-bacterial infection with two major viruses rotavirus (RV) and norovirus (NoV) and two pathogenic bacteria [Enteroaggregative E. coli (EAEC), and Enteropathogenic E. coli (EPEC)]. We sequenced 16S ribosomal RNA (V4 region) genes using Illumina MiSeq in 70 hospitalized children suffering from gastroenteric infections plus nine healthy controls. The study summarized Operational Taxonomic Unit (OTU) abundances with the Bray-Curtis index and performed a non-metric multidimensional scaling analysis to visualize microbiome similarities. We used a permutational multivariate analyses of variance to test the significance of group differences. We also analyzed the correlation between microbiome changes and clinical outcomes. Our data demonstrated a significant increase in the severity score in children with viral-bacterial mixed infections compared to those with virus infections alone. Statistical analysis by overall relative abundance denoted lesser proportions of Bacteroides in the infected children, whereas Bifidobacteriaceae richness was more prominent in the bacterial-viral mixed infections. Pairwise differences of gut microbiota were significantly higher in RV + EAEC (P = 0.009) and NoV + EAEC (P = 0.009) co-infections, compared to EPEC mixed infection with both, RV (P = 0.045) and NoV (P = 0.188). Shannon diversity index showed considerable more variation in microbiome diversity in children infected with RV cohort compared to NoV cohort. Our results highlight that richness of Bifidobacteriaceae, which acts as probiotics, increased with the severity of the viral-bacterial mixed infections. As expected, significant reduction of relative numbers of Bacteroides was characterized in both RV and NoV infections, with more reduction observed in co-infection pathogenic E. coli. Although mixed infection with EAEC resulted in significant microbiota differences compared to viral infection only or mixed infection with EPEC, the clinical condition of the children were worsened with both pathogenic E.coli co-infections. Further, in comparison with RV cohort, augmented number of differential abundant pathogenic OTUs were peculiarly noticed only with NoV mixed infection.

Metabolic derangements identified through untargeted metabolomics in a cross-sectional study of Nigerian children with severe acute malnutrition

Severe acute malnutrition (SAM) is a major cause of child mortality worldwide, however the pathogenesis of SAM remains poorly understood. Recent studies have uncovered an altered gut microbiota composition in children with SAM, suggesting a role for microbes in the pathogenesis of malnutrition. To elucidate the metabolic consequences of SAM and whether these changes are associated with changes in gut microbiota composition. We applied an untargeted multi-platform metabolomics approach [gas chromatography–mass spectrometry (GC-MS) and liquid chromatography–mass spectrometry (LC-MS)] to stool and plasma samples from 47 Nigerian children with SAM and 11 control children. The composition of the stool microbiota was assessed by 16S rRNA gene sequencing. The plasma metabolome discriminated children with SAM from controls, while no significant differences were observed in the microbial or small molecule composition of stool. The abundance of 585 features in plasma were significantly altered in malnourished children (Wilcoxon test, FDR corrected P < 0.1), representing approximately 15% of the metabolome. Consistent with previous studies, children with SAM exhibited a marked reduction in amino acids/dipeptides and phospholipids, and an increase in acylcarnitines. We also identified numerous metabolic perturbations which have not been reported previously, including increased disaccharides, truncated fibrinopeptides, angiotensin I, dihydroxybutyrate, lactate, and heme, and decreased bioactive lipids belonging to the eicosanoid and docosanoid family. Our findings provide a deeper understanding of the metabolic consequences of malnutrition. Further research is required to determine if specific metabolites may guide improved management, and/or act as novel biomarkers for assessing response to treatment.