Several factors are linked to the pathophysiology of autism spectrum disorders (ASD); however, the molecular mechanisms of the condition remain unknown. As intestinal problems and gut microbiota dysbiosis are associated with ASD development and severity, recent studies have focused on elucidating the microbiota-gut-brain axis' involvement. This study aims to explore mechanisms through which gut microbiota might influence ASD. Briefly, we depleted the microbiota of conventional male BALB/cAnNCrl (Balb/c) and C57BL/6J (BL/6) mice prior to human fecal microbiota transplantation (hFMT) with samples from children with ASD or their neurotypical siblings. We found mouse strain-specific responses to ASD hFMT. Notably, Balb/c mice exhibit decreased exploratory and social behavior, and show evidence of intestinal, systemic, and central inflammation accompanied with metabolic shifts. BL/6 mice show less changes after hFMT. Our results reveal that gut microbiota alone induce changes in ASD-like behavior, and highlight the importance of mouse strain selection when investigating multifactorial conditions like ASD.

Autism significantly impacts how individuals interact, communicate and perceive the world. Gastrointestinal disturbances, particularly constipation, are prevalent among autistic people, affecting their overall well-being. However, to the best of our knowledge, no specific guidelines are currently available regarding the diagnosis of constipation among this population. This systematic review investigates various diagnostic methods employed in studies addressing constipation among autistic adults. It aims to identify discrepancies between the symptoms reported based on diagnostic methods and the actual symptoms experienced by this population. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, nine studies conducted between 2012 and 2022 were included, revealing a predominance of non-prospective designs and an emphasis on children and adolescents. Diagnostic tools varied, including standardized criteria, questionnaires and observation. The prevalence of symptoms not outlined in the official criteria, such as sleep disorders and challenging behaviours, emerged as crucial aspects requiring comprehensive assessment in autistic people experiencing constipation. The study highlights the need for age-specific research in order to develop tailored assessment tools to improve diagnostic accuracy and enhance the overall management of constipation in autistic adults. Recognizing the diverse manifestations of constipation in this population is crucial for developing nuanced interventions and advancing healthcare strategies.Lay abstractAutistic people often experience gastrointestinal issues, with constipation being one of the most common concerns. However, there are currently no specific guidelines for diagnosing constipation in autistic adults. This makes it harder for healthcare providers to identify and treat the condition effectively. In this review, we analysed nine studies from 2012 to 2022 to understand the various methods used to diagnose constipation in autistic adults and their symptoms. We found that most studies used different approaches, such as questionnaires, standardized criteria, or observation. In addition, many studies focused on children and adolescents, leaving a gap in understanding symptoms in autistic adults. The studies highlighted symptoms that were not covered by official diagnostic criteria, such as sleep disturbances and challenging behaviours. This indicates a need for healthcare providers to consider a broader range of signs when diagnosing constipation in autistic people. Our review suggests that more research focusing on adults is needed to create tailored tools for diagnosing constipation in autistic adults. This will help improve accuracy and ensure better treatment outcomes. Understanding the unique ways constipation can present in autistic people is crucial for developing effective care strategies. For healthcare providers, this review emphasizes the importance of recognizing a wide range of symptoms when assessing constipation in autistic people. For policymakers, it highlights the need for age-specific guidelines to ensure that autistic adults receive the care and support they need. Further research will help refine these diagnostic tools and ultimately lead to better healthcare practices for autistic people.

Background/Objectives: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by difficulties in social interaction, communication, and repetitive behaviors. Recent evidence indicates a significant relationship between ASD and imbalances in microbiota, particularly in the oral and gastrointestinal areas. This review examines the impact of oral microbiota, self-injurious behaviors (SIB), sensory sensitivity, and dietary choices on the comorbidities associated with ASD. Methods: An extensive literature review was conducted using PubMed and Scopus. The focus was on human studies with full-text availability, utilizing search terms related to ASD, oral health, oral microbiota, and neurodevelopmental disorders. The research was evaluated for methodological quality and its relevance to the connections between microbiota, oral health, and ASD. Results: Individuals with ASD face unique oral health challenges, including injuries from self-injurious behaviors and increased sensory sensitivity, which complicate oral hygiene and care. Selective eating can lead to nutritional deficiencies and worsen oral health issues. Dysbiosis in oral and gut microbiota, marked by altered levels of acetate, propionate, and butyrate, interferes with gut-brain and oral-brain connections, contributing to behavioral and neurological symptoms. Treatment options such as probiotics, fecal microbiota transfer, and sensory integration therapies can potentially alleviate symptoms and improve quality of life. Conclusions: The relationship between ASD, oral health, and microbiota suggests a bidirectional influence through neuroinflammatory mechanisms and metabolic disturbances. Proactive strategies focusing on microbiota and dental health may help reduce comorbidities and enhance the overall management of ASD, underscoring the need for further research into microbiota-host interactions and their therapeutic potential.

The purpose of this retrospective cohort analysis was to investigate sex differences in receipt of standard of care sleep and constipation drug treatments among autistic children and youth with sleep disorder and constipation, respectively.

We used the data from the OneFlorida + Data Trust to analyze healthcare claims for 19,877 autistic patients with sleep disorder and 32,355 patients with constipation, ages 1 to 22. We used logistic regression to examine sex differences in receiving sleep and constipation treatments, and a multivariate logistic regression model to further assess sex differences in ever receiving sleep and constipation treatments, adjusting for age, race, ethnicity, and urbanicity.

In our multivariate analysis, autistic girls with sleep disorder were 1.27 times more likely than boys to receive sleep treatment (p < 0.0001). Although autistic girls with constipation appeared to be 1.10 times more likely than boys to receive treatment, it was not significantly different after adjusting for demographic and socio-economic characteristics (p = 0.372). Older children were 1.09 times more likely than younger children to receive sleep treatment (p < 0.0001) and 1.07 times more likely to receive constipation treatment (p < 0.0001).

We did not find sex differences among autistic children for treatment of constipation, but autistic girls with sleep disorder were significantly more likely to have ever received treatment, which could indicate that girls experience more significant sleep disorders.

The co-occurrence of autism and gastrointestinal distress is well-established, yet the molecular underpinnings remain unknown. The identification of high-confidence, large-effect autism genes offers the opportunity to identify convergent, underlying biology by studying these genes in the context of the gastrointestinal system. Here we show that the expression of these genes is enriched in human prenatal gut neurons and their migratory progenitors, suggesting that the development and/or function of these neurons may be disrupted by autism-associated genetic variants, leading to gastrointestinal dysfunction. Here we document the prevalence of gastrointestinal issues in patients with large-effect variants in sixteen autism genes, highlighting dysmotility, consistent with potential enteric neuron dysfunction. Using Xenopus tropicalis, we individually target five of these genes (SYNGAP1, CHD8, SCN2A, CHD2, and DYRK1A) and observe disrupted enteric neuronal progenitor migration for each. Further analysis of DYRK1A reveals that perturbation causes gut dysmotility in vivo, which can be ameliorated by treatment with either of two serotonin signaling modulators, identified by in vivo drug screening. This work suggests that atypical development of enteric neurons contributes to the gastrointestinal distress commonly seen in individuals with autism and that serotonin signaling may be a productive therapeutic pathway.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a complex etiology, including genetic and environmental factors. A growing body of evidence (preclinical and clinical studies) implicates a potential role of gut microbiome dysregulation in ASD pathophysiology. This review focuses on the microbial metabolite p-Cresol, produced by certain gut bacteria such as Clostridium, and its potential role in ASD. The review summarizes studies investigating the gut microbiome composition in ASD patients, particularly the increased abundance of Clostridium species and associated gastrointestinal symptoms. The potential neurotoxic effects of p-Cresol are explored, including its influence on neurotransmitter metabolism (especially dopamine), neuroinflammation, and brain development. The mechanistic findings from the preclinical studies of p-Cresol's induction of ASD-like behaviors and its impact on the dopaminergic system are discussed. Literature studies indicated increased levels of p-Cresol in the urine of patients with ASD. This increasing evidence suggests that p-Cresol may serve as a crucial biomarker for understanding the relationship between gut microbiota and ASD, opening avenues for potential diagnostic and therapeutic interventions.

Although the precise underlying cause(s) of autism spectrum disorder remain unclear, more than 1000 rare genetic variations are associated with the condition. For many people living with profound autism, this genetic heterogeneity has impeded the identification of common biological targets for therapy development for core and comorbid traits that include significant impairments in social communication and repetitive and restricted behaviors. A substantial number of genes associated with autism encode proteins involved in signal transduction and synaptic transmission that are critical for brain development and function. CAMK4 is an emerging risk gene for autism spectrum disorder that encodes the CaMK4 (calcium/calmodulin-dependent protein kinase 4) enzyme. CaMK4 is a key component of a Ca2+-activated signaling pathway that regulates neurodevelopment and synaptic plasticity. In this review, we discuss 3 genetic variants of CAMK4 found in individuals with hyperkinetic movement disorder and comorbid neurological symptoms including autism spectrum disorder that are likely pathogenic with monogenic effect. We also comment on 4 other genetic variations in CAMK4 that show associations with autism spectrum disorder, as well as 12 examples of autism-associated variations in other genes that impact CaMK4 signaling pathways. Finally, we highlight 3 environmental risk factors that impact CaMK4 signaling based on studies of preclinical models of autism and/or clinical cohorts. Overall, we review molecular, genetic, physiological, and environmental evidence that suggest that defects in the CaMK4 signaling pathway may play an important role in a common autism pathogenesis network across numerous patient groups, and we propose CaMK4 as a potential therapeutic target.

This study evaluated feeding problems and gastrointestinal symptoms in children with Silver-Russell syndrome (SRS), which is a rare epigenetic disorder. It also compared the symptoms experienced during different feeding methods, including percutaneous endoscopic gastrostomy (PEG).

The national expert team for children with SRS at Queen Silvia Children's Hospital, Gothenburg, studied 46 referrals (63% male) who were born with SRS in Sweden from 1984 to 2018. Patient data were extracted from the Paediatric National Growth Hormone Registry.

The medical records covered a median of 68% of the time of the patients' childhood, with a median follow-up of 9 years. Their symptoms were most prevalent during infancy and decreased when they were toddlers. Feeding problems and gastrointestinal symptoms were reported in 91% of the 46 patients, with vomiting in 57% and constipation in 46%. There were 19 children who relied on enteral feeding for their nutrition and 13 of those received PEG. Their body mass index (BMI) increased significantly 2 years after PEG started (p = 0.005).

Feeding problems and gastrointestinal symptoms were very common in children with SRS, but partly disappeared during childhood. Providing treatment, such as PEG, normalised the BMIs of children with SRS and reduced their symptoms.

Objective: To explore recent findings on how nutritional, gastrointestinal, social, and epigenetic factors interact in autism spectrum disorder, highlighting their implications for clinical management and intervention strategies that could improve development and quality of life of affected children. Sources: Studies published from 2000 to 2024 in the PubMed, Web of Science, Scopus, Scielo, Lilacs, and Google Scholar databases were collected. The process for the review adhered to the Search, Appraisal, Synthesis, and Analysis framework. Summary of the findings: Children with autism spectrum disorder have restrictive eating habits and often exhibit food selectivity with either hyper- or hypo-sensory characteristics. This review provides an overview of the literature on diagnosis and intervention strategies for selectivity in autism spectrum disorder, including the involvement of family members in meals, sharing a healthy diet and positive relationship with food, and the importance of exploring visual, olfactory, and tactile experiences of food and introducing new foods through play activities to expand the food repertoire. Modifications in the microbiota and gastrointestinal disorders may also be present in autism spectrum disorder and are presented due to their frequent nutritional repercussions. The medium and long-term implications of food preferences and behavior issues for nutritional status are also discussed, given the tendency for children with autism spectrum disorder to consume low-quality and energy-dense foods, leading to nutritional problems. Conclusions: Children with autism spectrum disorder have feeding difficulties, especially selectivity, gastrointestinal problems, changes in the microbiota and can evolve with micronutrient deficiencies, malnutrition and obesity. This review describes the evidence for possible targets for interventions aiming to improve nutritional health for children with autism spectrum disorder.

It is hypothesized that gut dysbiosis, a typical feature of patients with autism spectrum disorder (ASD), could be involved in the origin of this neurodevelopmental disorder. Therefore, the use of probiotics to restore gastrointestinal (GI) equilibrium might be a promising therapeutic strategy due to its capacity to balance the gut-brain axis and behavioral responses.

To summarize current knowledge on the use of probiotics to treat core clinical ASD symptoms and concomitant GI signs, compare the design of published studies with those of ongoing trials, assess the near future of this field, and provide recommendations for improving novel studies.

The literature search was conducted in February 2020 and updated in March 2021, using a broad range of bibliographic and clinical trial-specific databases.

Data were extracted using a standardized form, and articles reporting on 28 clinical studies (already published or still ongoing) were included. The risk of bias in clinical studies was evaluated using the Cochrane Collaboration Risk of Bias Assessment tool for randomized trials and the Risk of Bias in Nonrandomized Studies-Interventions tool for nonrandomized trials.

The results suggest that probiotics improve ASD-like social deficits, GI symptoms, and gut microbiota profile. However, inconsistencies among studies and their methodological limitations make it difficult to draw any conclusions regarding the efficacy of probiotics in ASD. This review provides specific suggestions for future research to improve the quality of the studies.

Although ongoing studies have improved designs, the available knowledge does not permit solid conclusions to be made regarding the efficacy of probiotics in ameliorating the symptoms (psychiatric and/or GI) associated with ASD. Thus, more high-quality research and new approaches are needed to design effective probiotic strategies for ASD.

The present study aimed to assess the psychiatric characteristics of children with chronic functional constipation using the Aberrant Behavior Checklist-Japanese version and the Pervasive Developmental Disorders/Autism Society Japan Rating Scale, and to examine the frequency of autism spectrum disorder in children with chronic functional constipation. We also investigated differences in treatment duration between children with and without autism spectrum disorder.

Treatment outcomes were examined retrospectively for 55 participants (chronic functional constipation group: n = 30, mean age 3.4 years; control group: n = 25, mean age, 4.5 years). The association between chronic functional constipation and autism spectrum disorder was evaluated using multivariable logistic regression analysis.

The mean Aberrant Behavior Checklist score and frequency of individuals with autism spectrum disorder were significantly higher in the chronic functional constipation group. After adjusting for age and sex, chronic functional constipation was significantly associated with autism spectrum disorder. In the chronic functional constipation group, the frequency of onset was significantly higher in children with autism spectrum disorder under 1 year of age. When treated, the mean duration of constipation was significantly longer in children with autism spectrum disorder.

Pediatricians, pediatric surgeons, and child psychiatrists should work closely to ensure appropriate treatment of chronic functional constipation in children with autism spectrum disorder.

Part I of this systematic review summarized the state-of-the-art of pediatric psychopharmacology for Autism Spectrum Disorder (ASD), a severe and lifelong neurodevelopmental disorder. The purpose of this Part II follow-up article is to provide a systematic overview of the experimental psychopharmacology of ASD. To this aim, we have first identified in the Clinicaltrials.gov website all the 157 pharmacological and nutraceutical compounds which have been experimentally tested in children and adolescents with ASD using the randomized placebo-controlled trial (RCT) design. After excluding 24 drugs already presented in Part I, a systematic review spanning each of the remaining 133 compounds was registered on Prospero (ID: CRD42023476555), performed on PubMed (August 8, 2024), and completed with EBSCO, PsycINFO (psychology and psychiatry literature) and the Cochrane Database of Systematic reviews, yielding a total of 115 published RCTs, including 57 trials for 23 pharmacological compounds and 48 trials for 17 nutraceuticals/supplements. Melatonin and oxytocin were not included, because recent systematic reviews have been already published for both these compounds. RCTs of drugs with the strongest foundation in preclinical research, namely arbaclofen, balovaptan and bumetanide have all failed to reach their primary end-points, although efforts to target specific patient subgroups do warrant further investigation. For the vast majority of compounds, including cannabidiol, vasopressin, and probiotics, insufficient evidence of efficacy and safety is available. However, a small subset of compounds, including N-acetylcysteine, folinic acid, l-carnitine, coenzyme Q10, sulforaphane, and metformin may already be considered, with due caution, for clinical use, because there is promising evidence of efficacy and a high safety profile. For several other compounds, such as secretin, efficacy can be confidently excluded, and/or the data discourage undertaking new RCTs. Part I and Part II summarize "drug-based" information, which will be ultimately merged to provide clinicians with a "symptom-based" consensus statement in a conclusive Part III, with the overarching aim to foster evidence-based clinical practices and to organize new strategies for future clinical trials.

The intestinal mucus layer protects the host from invading pathogens and is essential for maintaining a healthy mucosal microbial community. Alterations in the mucus layer and composition of mucus-residing microbiota in people diagnosed with autism may contribute to dysbiosis and gastrointestinal dysfunction. Although microbial dysbiosis based on sequencing data is frequently reported in autism, spatial profiling of microbes adjacent to the mucosa is needed to identify changes in bacterial subtypes in close contact with host tissues. Here, we analysed the spatial distribution of the mucin-2 protein using immunofluorescence as well as total bacteria, Bacteroidetes, Firmicutes phyla, and Akkermansia muciniphila using fluorescent in situ hybridization in mice expressing the autism-associated R451C variant in the Neuroligin-3 gene. We show that the Neuroligin-3 R451C variant increases mucus density adjacent to the distal ileal epithelium in mice. The relative density of total bacteria, Firmicutes, and A. muciniphila was increased whereas the density of Bacteroidetes was decreased closer to the epithelium in Neuroligin-3R451C mice. In summary, the autism-associated R451C variant in the Neuroligin-3 gene increases mucus density adjacent to the epithelium and alters microbial spatial distribution in the mouse distal ileum.

There is evidence that children with autism/autistic traits have higher risks of incontinence and constipation, but no studies have examined this in a large community-based cohort. Aim/Research question: are autistic traits and diagnosed autism prospectively associated with increased odds of incontinence and constipation in children and adolescents? This was a population-based cohort study based on data from the Avon Longitudinal Study of Parents and Children (n = 4233-4490 at age 9 years; n = 3403-3697 at age 14). We used multivariable logistic regression to examine associations of parent-reported autistic traits (sociability, repetitive behaviours, social-communication, coherence) (at ages 3-9 years) and autism with incontinence (bedwetting, daytime-wetting, soiling) and constipation (parent-reported at age 9, self-reported at age 14). We adjusted for parity, maternal age at delivery, child's sex and developmental level, maternal depression, and anxiety (antenatal and postnatal), and indicators of family socioeconomic status. Social-communication and speech coherence difficulties showed the strongest associations with incontinence, e.g., adjusted odds ratio (OR) and 95% confidence interval (CI) for the association between social-communication difficulties and daytime-wetting was 2.21 (1.47-3.32) and for coherence was 2.34 (1.60-3.43). The odds of soiling were also higher in children with social-communication (OR: 1.88, 95% CI 1.28-2.75) and coherence difficulties (OR: 2.04, 95% CI 1.43-2.93). Diagnosed autism was only associated with an increase in the odds of daytime-wetting (OR: 3.18, 95% CI 1.44-7.02). At 14 years, there was less evidence of associations between autistic traits and incontinence but there was evidence of associations between autistic traits and constipation: social-communication (OR: 1.68, 95% CI 1.13-2.49), coherence difficulties (OR: 1.64, 95% CI 1.11-2.41). Early assessment and treatment of incontinence/constipation should be considered for children with autistic traits.

Functional neurological disorder (FND) and autism spectrum disorder (ASD) are two complex neuropsychiatric conditions that have been historically classified within psychiatric domains, resulting in a lack of extensive research, insufficient clinical recognition, and persistent societal stigma. In recent years, there has been an increasing recognition among professionals and affected individuals of their possible overlap. This review explores the potential clinical and mechanistic overlap between FND and ASD, with particular attention to shared symptoms across sensory, motor, and psychiatric domains.

We conducted a narrative analysis utilizing the PubMed, CINAHL, MEDLINE, and ScienceDirect databases from inception to June 2024. The search employed specific MeSH terms related to ASD and FND. Given the limited data availability, we included all relevant articles that explored the potential connections between FND and ASD, focusing on established findings and theoretical hypotheses areas.

Scientific evidence indicates that FND and ASD may co-occur more frequently than previously acknowledged and with notable overlaps in their clinical presentations and pathophysiology. Theoretical models that have been applied to FND and ASD, such as the Bayesian brain theory and the tripartite model of autism, may provide valuable insights into the intersection of these conditions. Although much of the current evidence remains speculative, it underscores the need for hypothesis-driven research to investigate these potential connections further.

ASD and FND are heterogeneous conditions that appear to co-occur in a subset of individuals, with overlapping symptomatology and possibly shared underlying mechanisms. This hypothesis-generating review emphasizes the need for further research to better understand these links, ultimately aiming to improve clinical recognition and develop targeted interventions that enhance the quality of life for affected individuals.

What is already known about the topic?Autistic children frequently often have accompanying physical health problems. However, this has been much less studied in autistic men and women during adulthood.What does this article add?This is one of the first studies to investigate the associations between autistic and somatic problems in adults from the general population. Using a continuous measure of autistic symptom scores and a categorical definition of autism (referred to below as probable autism) which considered symptom severity, childhood age of onset, and functional impairment, we found that autistic problems and irritable bowel syndrome, food allergy, pain, and fatigue were associated in adults. Sex differences were present for pain and fatigue, for which the associations with autistic symptom scores were somewhat stronger in females than males. Regarding age differences, the associations with fatigue and having food allergy were more pronounced in younger adults. Conversely, older individuals had a higher risk of developing irritable bowel syndrome or experiencing pain if they met the criteria for probable autism.Implications for practice, research, or policyThere is a need for providing routine programs of screening, assessment, and treatment of autism-related somatic problems and developing evidence-based interventions for autistic individuals. These could be tailored to the needs of specific autistic populations. For example, autistic females could be given extra attention about the potential presence of pain and fatigue, younger adults about the potential presence of food allergy and fatigue, and older adults concerning the potential presence of irritable bowel syndrome and pain.

Autism spectrum disorder (ASD) often co-occurs with functional somatic syndromes (FSS), such as irritable bowel syndrome (IBS), multisite pain, and fatigue. However, the underlying genetic mechanisms and causality have not been well studied. Using large-scale genome-wide association study (GWAS) data, we investigated the shared genetic architecture and causality between ASD and FSS. Specifically, we first estimated genetic correlations and then conducted a multi-trait analysis of GWAS (MTAG) to detect potential novel genetic variants for single traits. Afterwards, polygenic risk scores (PRS) of ASD were derived from GWAS and MTAG to examine the associations with phenotypes in the large Dutch Lifelines cohort. Finally, we performed Mendelian randomization (MR) to evaluate the causality. We observed positive genetic correlations between ASD and FSS (IBS: rg = 0.27, adjusted p = 2.04 × 10-7; multisite pain: rg = 0.13, adjusted p = 1.10 × 10-3; fatigue: rg = 0.33, adjusted p = 5.21 × 10-9). Leveraging these genetic correlations, we identified 3 novel genome-wide significant independent loci for ASD by conducting MTAG, mapped to NEDD4L, MFHAS1, and RP11-10A14.4. PRS of ASD derived from both GWAS and MTAG were associated with ASD and FSS in Lifelines, and MTAG-derived PRS showed a bigger effect size, larger explained variance, and smaller p-values. We did not observe significant causality using MR. Our study found genetic associations between ASD and FSS, specifically with IBS, multisite pain, and fatigue. These findings suggest that a shared genetic architecture may partly explain the co-occurrence between ASD and FSS. Further research is needed to investigate the causality between ASD and FSS due to current limited statistical power of the GWASs.

The study of microbiome composition shows positive indications for application in the diagnosis and treatment of many conditions and diseases. One such condition is autism spectrum disorder (ASD). We aimed to analyze gut microbiome samples from children in Bosnia and Herzegovina to identify microbial differences between neurotypical children and those with ASD. Additionally, we developed machine learning classifiers to differentiate between the two groups using microbial abundance and predicted functional pathways.

A total of 60 gut microbiome samples (16S rRNA sequences) were analyzed, with 44 from children with ASD and 16 from neurotypical children. Four machine learning algorithms (Random Forest, Support Vector Classification, Gradient Boosting, and Extremely Randomized Tree Classifier) were applied to create eight classification models based on bacterial abundance at the genus level and KEGG pathways. Model accuracy was evaluated, and an external dataset was introduced to test model generalizability.

The highest classification accuracy (80%) was achieved with Random Forest and Extremely Randomized Tree Classifier using genus-level taxa. The Random Forest model also performed well (78%) with KEGG pathways. When tested on an independent dataset, the model maintained high accuracy (79%), confirming its generalizability.

This study identified significant microbial differences between neurotypical children and children with ASD. Machine learning classifiers, particularly Random Forest and Extremely Randomized Tree Classifier, achieved strong accuracy. Validation with external data demonstrated that the models could generalize across different datasets, highlighting their potential use.

Individuals with neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), often experience a higher prevalence of gastrointestinal (GI) symptoms but have complex medical and behavioral comorbidities that make diagnosis and treatment difficult. A multi-stakeholder conference was convened to (a) determine patient and family experiences related to GI symptoms in NDDs, (b) review the clinicians' and researchers' perspectives, and (c) determine actionable steps for future research.

The Consortium for Autism, Neurodevelopmental Disorders and Digestive Diseases (CANDID; www.candidgi.com) virtually over 2 days in 2022 and consisted of four key activities: (1) an electronic family survey to assess underlying NDDs and GI symptoms, (2) a session focused on family perspectives, (3) review current clinical care and research, and (4) discussion to identify key next steps. Survey results were obtained electronically via the REDCap platform, and descriptive statistics were generated. The sessions were recorded, and themes were identified.

The pre-conference survey ran for ~2 months and 739 families provided responses, with 634 completing all items. 83% had a child with an NDD under age 18, and most patients were White (85%) and non-Hispanic (87%). Constipation (80%), GI reflux disease (51%), and bloating (49%) were the most frequently reported symptoms. Families gave unstructured feedback that the measures used in the surveys were often difficult to answer for patients with NDDs or who were nonspeaking. Family and clinical/scientific sessions identified several common themes, including (1) the need for less invasive diagnostic modalities, (2) the need to validate or adapt existing diagnostic measures (e.g., the Rome IV criteria) and outcome assessments, and (3) the need for enhanced attention to parent and caregiver input in treatment plans.

Those providing care to children with NDDs, especially those with communication and cognitive challenges, should be aware of the differing needs in this community and consider family perspectives in managing, treating, and measuring GI issues. Future research should focus on adapting or creating diagnostic and research measures for those with NDDs, developing new diagnostic methods to account for diversity in neurodevelopment and communication, and improving methods for family and caregiver engagement in the care of GI disorders.

Autism spectrum disorder (ASD) is a multifactorial, pervasive, neurodevelopmental disorder, of which intestinal symptoms collectively represent one of the most common comorbidities.

In this study, 1,222 children with ASD and 1,206 typically developing (TD) children aged 2-7 years were enrolled from 13 cities in China. Physical measurement and basic information questionnaires were conducted in ASD and TD children. The Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), and Autism Behavior Checklist (ABC) were used to evaluate the clinical symptoms of children with ASD. The six-item Gastrointestinal Severity Index (6-GSI) was used to evaluate the prevalence of intestinal symptoms in two groups.

The detection rates of constipation, stool odor, and total intestinal symptoms in ASD children were significantly higher than those in TD children (40.098% vs. 25.622%, 17.021% vs. 9.287%, and 53.601% vs. 41.294%, respectively). Autistic children presenting with intestinal comorbidity had significantly higher scores on the ABC, SRS, CARS, and multiple subscales than autistic children without intestinal symptoms, suggesting that intestinal comorbidity may exacerbates the core symptoms of ASD children.

Intestinal dysfunction was significantly more common in autistic than in TD children. This dysfunction may aggravate the core symptoms of children with ASD.

Autism spectrum disorder (ASD) is associated with several coexisting diseases or comorbidities, including inflammatory and metabolic disorders. In fact, ASD symptoms may be associated with immune system dysfunction. However, studies investigating the peripheral blood levels of immune cells are lacking and have provided mixed findings. In this study, we evaluated the relationship between the intensity level of ASD symptoms and the inflammatory and metabolic profiles in 154 children and adolescents (2-17 years).

Bayesian multilevel models were used to examine the relationship between their symptom intensities and inflammatory/metabolic profiles.

Heavier children had higher values for triglyceride and insulin levels. Children with a level 3 of ASD intensity had higher free fatty acids levels. However, when adjusting for ASD intensity, gender, medication use, or weight status, older children appeared to have higher values of triglycerides, insulin levels, and free fatty acids.

We concluded that as Brazilian children with ASD became older, they had a higher risk for insulin resistance.

Physical health conditions are more common in individuals with autism. Some, like epilepsy, have considerable evidence supporting their increased prevalence, but many diseases lack literature to make strong conclusions.

To investigate the prevalence of physical health comorbidities in autism.

We undertook a nested cross-sectional study, using a sample from the National Centre for Mental Health database. It included participants from England and Wales who reported a clinician-made diagnosis of autism (n = 813), and a control sample without autism or mental illness (n = 2781). Participants had provided a medical history at enrolment. Analysis was carried out by binomial logistic regressions controlling for age, gender, smoking status, and antipsychotic and mood stabiliser use. A subanalysis of individuals with concurrent intellectual disability (n = 86) used binomial logistic regression with the same control variables.

Many physical health conditions were significantly more common in autism. Sixteen out of 28 conditions showed increased odds, with the highest odds ratios observed for liver disease, chronic obstructive pulmonary disease, kidney disease, osteoporosis and rheumatoid arthritis. A subanalysis demonstrated a similar pattern of physical health in individuals with autism with and without concurrent intellectual disability. Some conditions, including osteoporosis, hyperthyroidism, head injury and liver disease, had larger odds ratios in individuals with concurrent intellectual disability.

Physical health conditions occur more commonly in individuals with autism, and certain conditions are further increased in those with concurrent intellectual disability. Our findings contribute to prior evidence, including novel associations, and suggest that people with autism are at greater risk of physical health problems throughout adulthood.

Background: the intestinal microbiota, a complex community vital to human health, is shaped by microbial competition and host-driven selective pressures. Among these microbes, Bifidobacterium plays a crucial role in early gut colonization during neonatal stages, where Bifidobacterium longum subspecies infantis (B. infantis) predominates and is particularly prevalent in healthy breastfed infants. Objectives: as we embark on a new era in nutrition of the pediatric population, this study seeks to examine the existing understanding regarding B. infantis, encompassing both preclinical insights and clinical evidence. Methods: through a narrative disceptation of the current literature, we focus on its genetic capacity to break down various substances that support its survival and dominance in the intestine. Results: using "omics" technologies, researchers have identified beneficial mechanisms of B. infantis, including the production of short-chain fatty acids, serine protease inhibitors, and polysaccharides. While B. infantis declines with age and in various diseases, it remains a widely used probiotic with documented benefits for infant and child health in numerous studies. Conclusions: the current scientific evidence underscores the importance for ongoing research and clinical trials for a deeper understanding of B. infantis's role in promoting long-term health.

Our previous study revealed that feeding the antimicrobial peptide (AMP) product Scy-hepc significantly enhances the growth of mariculture fish through the activation of the GH-Jak2-STAT5-IGF1 axis. However, the contribution of gut microbiota to this growth enhancement remains unclear. This study aimed to elucidate the potential mechanism involved in intestinal absorption and modulation of gut microbiota in Epinephelus akaara following Scy-hepc feeding.

The results showed that a 35 day regimen of Scy-hpec markedly promoted the growth of E. akaara compared to groups supplemented with either florfenicol, B. subtilis, or a vector. The growth enhancement is likely attributed to alterations in microbiota colonization in the foregut and midgut, characterized by an increasing abundance of potential probiotics (Rhizobiaceae and Lysobacter) and a decreased abundance of opportunistic pathogens (Psychrobacter and Brevundimonas) as determined by 16S rRNA analysis. Additionally, similar to the effect of florfenicol feeding, Scy-hepc significantly improved host survival rate by over 20% in response to a lethal dose challenge with Edwardsiella tarda. Further investigations demonstrated that Scy-hepc is absorbed by the fish foregut (20-40 min) and midgut (20-30 min) as confirmed by Western blot, ELISA, and Immunofluorescence. The absorption of Scy-hepc affected the swimming, swarming and surfing motility of Vibrio harveyi and Bacillus thuringiensis isolated from E. akaara's gut. Moreover, Scy-hepc induced the downregulation of 40 assembly genes and the upregulation expression of 5, with the most significant divergence in gene expression between opportunistic pathogens and probiotics concentrated in their motility genes (PomA/B, MotA/B).

In summary, this study shows that feeding AMP Scy-hepc can promote growth and bolster immunity in E. akaara. These beneficial effects are likely due to the absorption of Scy-hepc in the fish's foregut and midgut, which modulates the colonization and motility of commensal bacteria, leading to favorable changes in the composition of the foregut and midgut microbiota. Therefore, a profound understanding of the mechanisms by which antimicrobial peptides affect host gut microbiota will contribute to a comprehensive assessment of their advantages and potential application prospects as substitutes for antibiotics in fish health and improving aquaculture practices.

Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by social, behavioral, and cognitive impairments. Several comorbidities, including gastrointestinal (GI) dysregulations, are frequently reported in ASD children. Although studies in animals have shown the crucial role of the microbiota in key aspects of neurodevelopment, there is currently no consensus on how the alteration of microbial composition affects the pathogenesis of ASD. Moreover, disruption of the gut-brain axis (GBA) has been reported in ASD although with limited studies conducted on the Mediterranean population. In our study, we aimed to investigate gut microbiota composition in Lebanese ASD subjects, their unaffected siblings, and a control group from various regions in Lebanon using the 16 S-rRNA sequencing (NGS). Our study revealed a lower abundance of Turicibacter and a significant enrichment on Proteobacteria in the ASD and siblings' groups compared to the controls, indicating that gut microbiota is probably affected by dietary habits, living conditions together with host genetic factors. The study also showed evidence of changes in the gut microbiome of ASD children compared to their siblings and the unrelated control. Bacteroidetes revealed a lower abundance in the ASD group compared to controls and siblings, conversely, Catenibacterium and Tenericutes revealed an increased abundance in the ASD group. Notably, our study identifies alterations in the abundance of Turicibacter and Catenibacterium in ASD children suggesting a possible link between these bacterial taxa and ASD and contributing to the growing body of evidence linking the microbiome to ASD.

Aging brings about physiological dysfunction, disease, and eventual mortality. An increasing number of studies indicate that aging can easily lead to dysbiosis of the gut microbiota, which can further affect digestion, nerves, cognition, emotions, and more. Therefore, gut bacteria play an important role in regulating the physical functions of aging populations. While saponins, the primary components of American ginseng, are frequently utilized for treating common ailments in the elderly due to their potent antioxidant properties, there is a scarcity of comprehensive studies on aging organisms. This study focused on 18 month old aging mice and investigated the effects of single intervention and combined intervention of Rb1 and Re, the main components of Panax quinquefolium saponins, on the gut microbiota of aging mice. High throughput 16s RNA gene sequencing analysis was performed on the gut contents of the tested mice, and the results showed that Rb1 and Re had a significant impact on the gut microbiota. Rb1, Re, and Rb1 + Re can effectively enhance the diversity of gut microbiota, especially in the combined Rb1 + Re group, which can recover to the level of young mice. Re can promote the abundance of probiotics such as Lactobacillus, Lactobacillaceae, and Lactobacillus, and inhibit the abundance of harmful bacteria such as Enterobacteriaceae. This indicates that the intervention of Rb1, Re, and Rb1 + Re can maintain the homeostasis of gut microbiota, and the combined application of Rb1 + Re has a better effect. The relationship between aging, brain gut axis, and gut microbiota is very close. Saponins can improve the gut microbiota of aging individuals by maintaining the balance of gut microbiota and the normal function of the brain gut axis, enabling the body to achieve a gut microbiota homeostasis closer to that of young healthy mice.

Characteristics of children with impaired development who have acute appendicitis are not well described in the literature.

We reviewed the National Surgical Quality Improvement Program-Pediatric and the multicenter Pediatric Health Information System for patients with acute appendicitis. Comparisons for demographics, clinical outcomes, and hospital charges between children with impaired development versus neurotypical children were made using independent t test or Wilcoxon rank sum tests. The multivariable logistic regression model estimated the odds of complicated acute appendicitis in impaired development patients. Based on correlation analyses, hierarchical linear modeling was used to examine the extent to which impaired development influenced resource use.

Patients with impaired development were younger, had higher comorbidities, and were more commonly male sex. In the National Surgical Quality Improvement Program-Pediatric database, impaired development was associated with higher rates of complicated acute appendicitis (33.6% vs 27.5, P < .001), particularly in older children, and higher usage of computed tomography at National Surgical Quality Improvement Program-Pediatric hospitals (23.1% vs 15.1%, P < .001). In the Pediatric Health Information System database, the adjusted odds of complicated acute appendicitis were significantly higher in patients with impaired development (1.20 [1.09-1.31]), low childhood opportunity level (1.39 [95% confidence interval: 1.31-1.47]), and Black race (1.25 [1.17-1.33]). Hierarchical adjusted linear modeling showed that impaired development was associated with significantly higher hospital charges (9% increase).

Management of acute appendicitis in children with impaired development remains a challenge to clinicians, as evidenced by the higher rate of perforated appendicitis in older children, diagnostic computed tomography use at National Surgical Quality Improvement Program-Pediatric hospitals, postoperative computed tomography use, and increased costs.

An expert commission has proposed the term "profound" autism for children on the spectrum who are minimally verbal or nonverbal and have intellectual disability (ID), behavioral challenges, and co-occurring conditions. It is unknown whether parents' rating of "severe" autism aligns with the definition of "profound" autism. Using the National Survey of Children's Health, we sought to (1) estimate the prevalence of parent-reported severe autism, (2) identify child characteristics that are associated with severe autism, (3) compare health care utilization, and (4) compare caregiver stress and resilience between families of children with severe versus mild/moderate autism.

Parent responses on the 2018 to 2019 NSCH were used to compare school-age children with parent-reported severe autism and those with mild/moderate autism. Descriptive statistics, χ 2 tests, and logistic regression were used for statistical analysis.

Among parents of 1,368 US children with autism, 10.1% characterized their child's autism as severe, a prevalence of 1 in 333. Parents of children with severe autism were more likely to report ID (45% vs 12.1%, p < 0.001), language delay (88% vs 58.7%, p < 0.001), and difficulties in dressing and bathing (67% vs 19.2%, p < 0.001). Children with severe autism had more behavioral problems and co-occurring conditions but were no more likely to see specialists or receive autism-specific behavioral therapy. Their caregivers reported more stress and less resilience.

The characteristics of "profound" autism and parent-reported "severe" autism significantly overlap, allowing the use of the NSCH for studies of this vulnerable population. Children with profound/severe autism could benefit from more behavioral therapy, specialty care, and family support.

Autism spectrum disorder (ASD) is a cluster of neurodevelopmental disorders characterized by deficits in communication and behavior. Increasing evidence suggests that the microbiota-gut-brain axis and the likely related immune imbalance may play a role in the development of this disorder. Gastrointestinal deficits and gut microbiota dysfunction have been linked to the development or severity of autistic behavior. Therefore, treatments that focus on specific diets may improve gastrointestinal function and aberrant behavior in individuals with ASD. In this study, we investigated whether a diet containing specific prebiotic fibers, namely, 3% galacto-oligosaccharide/fructo-oligosaccharide (GOS/FOS; 9:1), can mitigate the adverse effects of in utero exposure to valproic acid (VPA) in mice. Pregnant BALB/cByJ dams were injected with VPA (600 mg/kg, sc.) or phosphate-buffered saline (PBS) on gestational day 11 (G11). Male offspring were divided into four groups: (1) in utero PBS-exposed with a control diet, (2) in utero PBS-exposed with GOS/FOS diet, (3) in utero VPA-exposed with a control diet, and (4) in utero VPA-exposed with GOS/FOS diet. Dietary intervention started from birth and continued throughout the duration of the experiment. We showed that the prebiotic diet normalized VPA-induced alterations in male offspring, including restoration of key microbial taxa, intestinal permeability, peripheral immune homeostasis, reduction of neuroinflammation in the cerebellum, and impairments in social behavior and cognition in mice. Overall, our research provides valuable insights into the gut-brain axis involvement in ASD development. In addition, dietary interventions might correct the disbalance in gut microbiota and immune responses and, ultimately, might improve detrimental behavioral outcomes in ASD.

Background and objectives This study aimed to explore the frequency of gastrointestinal (GI) symptoms and associated risk factors among children with autism spectrum disorder (ASD). Methods This was a retrospective case-control study including children aged 2-14 years diagnosed with ASD by the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria and the assessment card in the ASD center at King Salman Armed Forces Hospital. Data were obtained using a self-developed questionnaire that included demographic features, nutritional and behavioral characteristics, and GI symptoms in the previous six months. The control group consisted of typically developing (TD) children matched to the ASD group for age and gender. Syndromic autism with defined somatic abnormalities and recognized genetic causes (e.g., fragile X syndrome, tuberous sclerosis) were excluded Results A total of 146 ASD children and 114 normal children were included. No significant demographic differences were found between the groups. The ASD group had a higher frequency of low income and a significantly lower rate of exclusive breastfeeding in the first six months. GI symptoms, specifically constipation, abdominal gases and distension, diarrhea, undigested food particles in stool, and mouth ulcers, were significantly more frequent in the ASD group. Weight abnormalities (both increase and decrease) were also more common. Family history of ASD was significantly more in ASD children with GI symptoms while low maternal education was more in those without. Conclusion This study reveals a high prevalence of GI symptoms in ASD children. Family history of ASD and maternal education may influence the GI symptoms reported in ASD children.

Children diagnosed with autism spectrum disorder (ASD) are at an increased risk of experiencing gastrointestinal (GI) discomfort, which has been linked to dysfunctions in the microbiome-gut-brain axis. The bidirectional communication between gut and brain plays a crucial role in the overall health of individuals, and alterations in the gut microbiome can contribute to immune activation and gut-brain dysfunction in ASD. Despite the limited and controversial results of pre-/probiotic applications in ASD, this review comprehensively maps the association between ASD clinical symptoms and specific bacterial taxa and evaluates the efficacy of pre-/probiotics in modulating microbiota composition, reducing inflammatory biomarkers, alleviating difficulties in GI distress, sleep problems, core and other ASD-associated symptoms, as well as relieving parental concerns, separately, in individuals with ASD. Beyond simply targeting core ASD symptoms, this review highlights the potential of pre-/probiotic supplementations as a strategy to modulate gut homeostasis and immune response, and to delineate the potential mechanisms by which its direct or mediating effects can alleviate gut-brain dysfunction and poor nutritional status in ASD management. Further well-designed randomized controlled trials are needed to strengthen the existing evidence and establish optimal protocols for the use of pre-/probiotics in the context of ASD.

Neurodevelopmental disorders are rapidly increasing in prevalence and have been linked to various environmental risk factors. Mounting evidence suggests a potential role of vitamin D in child neurodevelopment, though the causal mechanisms remain largely unknown. Here, we investigate how vitamin D deficiency affects children's communication development, particularly in relation to Autism Spectrum Disorder (ASD). We do so by developing an integrative network approach that combines metabolomic profiles, clinical traits, and neurodevelopmental data from a pediatric cohort. Our results show that low levels of vitamin D are associated with changes in the metabolic networks of tryptophan, linoleic, and fatty acid metabolism. These changes correlate with distinct ASD-related phenotypes, including delayed communication skills and respiratory dysfunctions. Additionally, our analysis suggests the kynurenine and serotonin sub-pathways may mediate the effect of vitamin D on early life communication development. Altogether, our findings provide metabolome-wide insights into the potential of vitamin D as a therapeutic option for ASD and other communication disorders.

Sensory processing challenges are commonly encountered in pediatric patients, particularly in those who are neurodivergent. We previously developed a novel clinical pathway (named "Sensory Pathway") which aimed at improving patient care for those with sensory barriers via staff training, provision of sensory toolkits and early integration of families throughout the hospital stay. We hypothesized that utilization of this pathway will result in improved patient experience and provide valuable feedback to improve care.

A voluntary survey was made available to all patients who utilized this resource as part of our hospital wide patient satisfaction survey. Qualitative data was coded using open coding as part of the constant comparison method data using NVivo 12 for Windows software for analysis. Software was used to create word clouds and clusters for visualization, which confirmed the themes and patterns that were noted from initial open coding.

Between 2021 and 2022, surveys were obtained from 160 patients who utilized the Sensory Pathway. More than 50% reported that the most helpful components of the pathway were the approach by the staff and sensory tools. The three major themes identified from the survey were (1) Tools and techniques that benefited their children; (2) Positive interactions and communication with the hospital staff, and (3) Suggestions for future improvement.

The survey results highlight the importance of having tools readily available to aid with sensory regulation and comfort of patients during healthcare encounters, the value of a positive patient and staff encounter, as well as opportunities for improvement.

The gut microbiota is believed to influence neurodevelopment through the gut-brain axis, but prior studies have shown inconsistent results regarding early childhood antibiotic exposure and subsequent risk of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). The purpose of this study was to evaluate the hypothesis that exposure to antibacterial agents in the first 2 years of life increases the risk of ASD and/or ADHD.

This was a retrospective cohort study using 2003-2019 data from the National Health Insurance Research Database in Taiwan. Livebirths born between 2004 and 2016 were identified and separated into singleton, full sibling, and exposure-discordant sibling pair cohorts. The exposure group included children who filled at least one prescription for antibacterial agents between 0 and 2 years old in outpatient settings. The outcome, ASD and/or ADHD, was defined by at least one inpatient or outpatient diagnosis. The maximum follow-up age was 15 years in this study. Potential neonatal, maternal and paternal confounders were adjusted for. Cox proportional hazards models were used to estimate the relative event risk.

The final sample contained 946,581 children in the singleton cohort, 1,142,693 children in the full sibling cohort, and 352,612 children in the exposure-discordant sibling pair cohort. Antibiotic exposure marginally increased the risk of ASD and/or ADHD in the singleton cohort (adjusted hazard ratio [aHR]: 1.06, 95% confidence interval [CI]: 1.04-1.07) and in the full sibling cohort (aHR: 1.03, 95% CI: 1.01-1.04). A slight decrease in the risk of ASD and/or ADHD was observed in the exposure-discordant sibling pair cohort (aHR: 0.92, 95% CI: 0.90-0.94).

The results suggest that early life antibiotic exposure has minimal impact on the risk of ASD and/or ADHD. Given that the estimated effects are marginal and close to null, concerns about ASD and/or ADHD risk increase should not postpone or deter timely and reasonable antibiotic use.

The comorbidity of autism spectrum disorders and severe gastrointestinal symptoms is well-established, yet the molecular underpinnings remain unknown. The identification of high-confidence large-effect autism risk genes offers the opportunity to identify convergent, underlying biology by studying these genes in the context of the gastrointestinal system. Here we show that the expression of these genes is enriched in human prenatal gut neurons as well as their migratory progenitors, suggesting that the development and/or function of these neurons may be disrupted by autism-associated pathogenic variants, leading to gastrointestinal dysfunction. Here we document the prevalence of gastrointestinal issues in patients with large-effect variants in sixteen of these genes, highlighting dysmotility, consistent with potential enteric neuron dysfunction. Using the high-throughput diploid frog Xenopus tropicalis , we individually target five of these genes ( SYNGAP1, CHD8, SCN2A, CHD2 , and DYRK1A ) and observe disrupted enteric neuronal progenitor migration for each. More extensive analysis of DYRK1A reveals that perturbation causes gut dysmotility in vivo , which can be ameliorated by treatment with a selective serotonin reuptake inhibitor (escitalopram) or a serotonin receptor 6 agonist, identified by in vivo drug screening. This work suggests that atypical development of enteric neurons contributes to the gastrointestinal distress commonly seen in individuals with autism and that increasing serotonin signaling may be a productive therapeutic avenue.

The neural network of the enteric nervous system (ENS) underlies gastrointestinal functions. However, the molecular mechanisms involved in enteric neuronal connectivity are poorly characterized. Here, we studied the role of semaphorin 5A (Sema5A), previously characterized in the central nervous system, on ENS neuronal connectivity. Sema5A is linked to autism spectrum disorder (ASD), a neurodevelopmental disorder frequently associated with gastrointestinal comorbidities, and potentially associated with ENS impairments. This study investigated in rat enteric neuron cultures and gut explants the role of Sema5A on enteric neuron connectivity and the impact of ASD-associated mutations on Sema5A activity. Our findings demonstrated that Sema5A promoted axonal complexity and reduced functional connectivity in enteric neurons. Strikingly, the ASD-associated mutation S956G in Sema5A strongly affected these activities. This study identifies a critical role of Sema5A in the ENS as a regulator of neuronal connectivity that might be compromised in ASD.

Constipation is prevalent worldwide, significantly increasing healthcare costs and diminishing the quality of life in children affected. Current studies have yielded mixed results regarding the factors associated with constipation, and mainly focusing on patients outside of Asia. Moreover, most of these studies lack focus on the paediatric population. This study aimed to identify the prevalence and associated factors of constipation among children in Asia.

In this systematic review and meta-analysis, we systematically searched PubMed, Scopus, and Cochrane for cohort and cross-sectional studies published from database inception up to October 12, 2022, and continued with manual searching until September 2, 2023. Eligible studies were those that included children in Asia aged 0-18 years old suffering from idiopathic constipation, with prevalence value provided in the English abstract. The analysis included clinical and general population. Children with organic constipation, who had undergone gastrointestinal surgery, or with congenital defects were excluded, as these factors affect the incidence of constipation. Data included in the analysis were extracted from published reports only. The extracted data were pooled using random-effects model to analyse the prevalence of constipation in children in Asia. This study is registered with PROSPERO, CRD42022367122.

Out of 4410 systematically searched studies and 36 manually searched ones, a total of 50 studies were included in the final analysis, encompassing data from 311,660 children residing in Asia. The pooled prevalence of constipation was 12.0% (95% CI 9.3-14.6%, I2 = 99.8%). There was no significant difference in constipation prevalence observed by sex and geographical location. Nonetheless, adolescents and children aged 1-9 years exhibited a significantly higher prevalence constipation compared to infants (p < 0.0001) Additionally, significant differences in constipation rates were observed across various diagnostic methods, population sources, and mental health conditions.

Despite the high heterogeneity resulting from varying diagnostic tools or definitions used among studies, our review adds to the literature on constipation among children in Asia. It reveals a notably high prevalence of constipation in this demographic. Diagnostic methods, age, and compromised mental health emerged as significant influencers of constipation among children in Asia, highlighting potential strategies to mitigate constipation prevalence in children in Asia.

The National Science and Technology Council, Taiwan.

Autism spectrum disorder (ASD) is a multifactorial, pervasive neurodevelopmental disorder affecting 1 in 36 children in the United States. Given the rising prevalence and significant economic and social costs associated with ASD, it is critical that continued efforts be made towards better understanding the underlying etiology as well as management of the condition and its commonly associated comorbidities. It has been estimated that upwards of 70% of children with ASD have a positive history of gastrointestinal (GI) symptoms. In this retrospective, descriptive study, we identified 131 patients with diagnosis of autism spectrum disorder who presented for initial evaluation by pediatric gastroenterology at the Baystate Children's Specialty Center. We collected data from chart review of these patients with a particular focus on reason for referral, components of evaluation as well as results of said evaluation. Of the 131 patients, the most frequent reason for referral included constipation (42.7%), abdominal pain (27.5%), and feeding difficulties (26.7%). After completion of the evaluation, 60.3% of patients were ultimately diagnosed with a functional gastrointestinal condition. Of patients who completed endoscopic evaluation, 40% of patients were found to have grossly abnormal and 40% were found to have pathologically abnormal EGD. The majority of patients were recommended to have diagnostic evaluation; however, a large proportion of them were unable to complete said evaluation. The majority of patients were found to have abnormal testing; however, the majority of patients were additionally diagnosed with a functional gastrointestinal condition.

This study has followed a birth cohort for over 20 years to find factors associated with neurodevelopmental disorder (ND) diagnosis. Detailed, early-life longitudinal questionnaires captured infection and antibiotic events, stress, prenatal factors, family history, and more. Biomarkers including cord serum metabolome and lipidome, human leukocyte antigen (HLA) genotype, infant microbiota, and stool metabolome were assessed. Among the 16,440 Swedish children followed across time, 1,197 developed an ND. Significant associations emerged for future ND diagnosis in general and for specific ND subtypes, spanning intellectual disability, speech disorder, attention-deficit/hyperactivity disorder, and autism. This investigation revealed microbiome connections to future diagnosis as well as early emerging mood and gastrointestinal problems. The findings suggest links to immunodysregulation and metabolism, compounded by stress, early-life infection, and antibiotics. The convergence of infant biomarkers and risk factors in this prospective, longitudinal study on a large-scale population establishes a foundation for early-life prediction and intervention in neurodevelopment.