Autism spectrum disorder (ASD) is a developmental disorder that is characterized by deficits in social communication and restricted, repetitive, and stereotyped behaviors. In addition to neurobehavioral symptoms, children with ASD often have gastrointestinal symptoms (e.g. constipation, diarrhea, gas, abdominal pain, reflux). Several studies have proposed the role of gut microbiota and metabolic disorders in gastrointestinal symptoms and neurodevelopmental dysfunction in ASD patients; these results offer promising avenues for novel treatments of this disorder. Interventions targeting the gut microbiota - such as fecal microbiota transplant (FMT), microbiota transplant therapy (MTT), probiotics, prebiotics, synbiotics, antibiotics, antifungals, and diet - promise to improve gut health and can potentially improve neurological symptoms. The modulation of the gut microbiota using MTT in ASD has shown beneficial and long-term effects on GI symptoms and core symptoms of autism. Also, the modulation of the gut microbiota to resemble that of typically developing individuals seems to be the most promising intervention. As most of the studies carried out with MTT are open-label studies, more extensive double-blinded randomized control trials are needed to confirm the efficacy of MTT as a therapeutic option for ASD. This review examines the current clinical research evidence for the use of interventions that target the microbiome - such as antibiotics, antifungals, probiotics/prebiotics, synbiotics, and MTT - and their effectiveness in changing the gut microbiota and improving gastrointestinal and neurobehavioral symptoms in ASD.

Gastrointestinal (GI) symptoms are frequently reported in children with autism spectrum disorder (ASD) and may significantly impact behavior, sleep, adaptive functioning, and the severity of autism. This study aims to explore the relationship between GI symptoms and these factors in children with ASD.

We investigated 96 children and adolescents with ASD aged 3-18 years attending an autism clinic in South India. Parents were interviewed using a semi-structured proforma that gathered information on GI symptoms, sociodemographic details, medical history, and treatment history. Behavioral problems were assessed using the Strengths and Difficulties Questionnaire-2 (SDQ-2), ASD severity was measured using the Indian Scale for Assessment of Autism (ISAA), and sleep issues were evaluated using the Children's Sleep Habits Questionnaire (CSHQ) for autism. Statistical analyses were conducted to determine the predictive value of assessment scores on GI symptoms in two groups: (a) those with mild to moderate ASD and (b) participants aged less than or equal to six years versus more than six years.

Constipation and dietary problems were the most commonly reported (82.29%), followed by dyspepsia and reflux (44.79%), pica (36.46%), abdominal pain (26.04%), and diarrhea (14.58%). Holding all other predictor variables constant, constipation increased by 20% (odds ratio [OR] = 1.201) for unit increases in speech-language communication scores. Abdominal pain decreased by 24.5% (OR = 0.755) for unit increases in peer problems scores. Excessive flatulence decreased by 64.2% (OR = 0.358) for unit increases in conduct problems score. Finally, pica was found to increase by 23.2% (OR = 1.232) for unit increases in the sensory patterns score.

The GI symptoms can negatively impact sleep and behavior in children with ASD, spotlighting the importance of routine GI screening in this population. Clinicians should be particularly vigilant in cases where symptoms suggest a higher likelihood of GI issues to enhance the quality of care for children with ASD.

Neurodevelopmental disorders (NDDs) encompass a range of disruptive conditions with varying prevalence rates and multiple contributing factors. Recent studies have suggested a potential connection between NDDs and the gut-brain axis. Furthermore, there is evidence indicating that nutritional supplements might have an impact on gastrointestinal (GI) and behavioral symptoms. This study aimed to explore the effects of nutritional supplements on the gut microbiota and behavioral symptoms in individuals with NDDs.

A systematic search of databases such as PubMed, Scopus, Web of Science, Embase, and APA PsycINFO was conducted, utilizing relevant keywords until February 2025. In addition, the search for gray literature was carried out on Google Scholar and ProQuest. The risk of bias was assessed using the ROBINS-I tool for non-randomized studies and the RoB-1 tool for randomized controlled trials. Due to the heterogeneity of the studies, a Synthesis without Meta-analysis (SWiM) approach was employed.

The overall findings from the studies indicated positive effects of supplementation in reducing the Gastrointestinal Severity Index (GIS) score and alleviating GI symptoms. Supplementation with probiotics and vitamins increased good microbiomes (GM) and decrease in bad microbiomes (BM) among individuals with autism spectrum disorder (ASD). Moreover, the Firmicutes to Bacteroidetes ratio (F/R ratio) exhibited significant changes after supplementation. Additionally, improvements were observed in various assessment scores, including ATEC, ABC, CARS, and PGI-2.

Nutritional supplementation in individuals with NDDs can have a positive influence by modulating the microbiome, reducing dysbiosis, and enhancing gut barrier integrity. Shifting in the F/R ratio can be considered as the reason for improving gastrointestinal and behavioral symptoms by influencing neurotransmitter activity and neuroinflammation. Targeting the gut-brain axis with interventions that focus on gut microbiota offers a promising adjunct therapy for the management of NDD. Registration of the review protocol. PROSPERO registration no. CRD42023460449.

To investigate whether probiotic supplementation can improve behavioural and gastrointestinal (GI) symptoms in children with autism spectrum disorder (ASD) aged 2-9 years and further explore the correlation between these symptoms.

Single-blinded, randomised, placebo-controlled study.

Five developmental paediatric outpatient clinics of 'Continua Kids'.

Children aged 2-9 years diagnosed with ASD along with their caregivers.

Probiotic or placebo sachet reconstituted in 50 mL of lukewarm milk/water, taken two times per day for 3 months.

Change in behavioural (measured by Social Responsiveness Scale-2 (SRS-2) and Aberrant Behaviour Checklist-2 (ABC-2) tools) and GI (measured by GI Severity Index (GSI) score) symptoms after receiving intervention for 3 months.

A total of 180 children with ASD were enrolled in the study (probiotic group: 90 and placebo group: 90). All children completed the study. The probiotic group showed a significant reduction in behavioural symptom severity as measured by the SRS-2 tool (47.77% vs 23.33%; p=0.000) compared with the placebo. Probiotic-treated children demonstrated significant reductions in severe symptoms, including social withdrawal/lethargy (40%), stereotypic behaviour (37.77%), hyperactivity (34.44%) and inappropriate speech (32.22%) post-intervention (p=0.000). They also had marked improvements in constipation (p=0.003) and diarrhoea (p=0.043) compared with the placebo group. Both groups exhibited a statistically significant correlation between behavioural and GI symptoms.

Probiotic supplementation improved behavioural and GI symptoms in children with ASD with no adverse effects. Both symptoms were significantly correlated. However, these results need to be validated in a larger sample size.

CTRI/2021/11/038213.

Gastrointestinal (GI) difficulties are common in children diagnosed with autism spectrum disorder (ASD). However, these difficulties can frequently remain unrecognized. Therefore, we aimed to translate a newly developed instrument, The Autism Spectrum Disorder Gastrointestinal and Related Behaviors Inventory in Children (ASD-GIRBI), to assess its reliability and to explore the frequency of various gastrointestinal difficulties and related behaviors, as well as to explore the association of GI difficulties with the measures of social functioning and emotional and behavioral difficulties in children with ASD. A total of 98 children and adolescents (aged 4-18 [M age = 10.67 ± 3.705], 82.7% male), previously diagnosed with ASD at the Institute of Mental Health in Belgrade, Serbia, took part in this research. Their parents filled out the following questionnaires: ASD-GIRBI (an assessment of gastrointestinal and related symptoms), Stanford Social Dimensions Scale (SSDS) (a measure of social functioning) and Strengths and Difficulties Questionnaire (SDQ) (a measure of emotional and behavioral problems). Our results indicate that the ASD-GIRBI is a reliable instrument for GI difficulties assessment (Cronbach's α = 0.841) with the total score successfully discriminating between the participants with and without a GI disorder diagnosis (p = 0.040). Any gastrointestinal symptom was present in 54.1% of the participants, most commonly flatulence, diarrhea, and constipation. The severity of gastrointestinal difficulties correlated to emotional problems (r = 0.261, p < 0.01), conduct problems (r = 0.219, p < 0.05), hyperactivity (r = 0.381, p < 0.01), peer problems (r = 0.266, p < 0.01), total difficulties (r = 0.454, p < 0.01) and total difficulties impact (r = 0.321, p < 0.01). Our data emphasize the potential importance of GI difficulties for various areas of functioning of individuals with ASD.

ASD is a complex condition defined by many causes, one of them being excessive concentrations of necessary and harmful chemicals in children. The serum, hair, and nails of children with ASD have lower levels of critical trace elements, according to studies. It is quite obvious that bio elements are involved in physiology and pathophysiology. Thus, this study examined trace element contents in serum samples from children with autism spectrum disorder (ASD), specifically zinc (Zn), aluminum (Al), and selenium (Se). The study also looked for links between trace element levels and autistic severity. The study included 47 children with autism spectrum disorder, and the Gilliam's Scale was used for severity. The study also included 53 healthy kids with age and gender-matched with those of ASD. For serum trace element analysis, graphite furnace atomic absorption spectrophotometry was used. The study found significant decreases in selenium and zinc concentration (OR, 5.25; CI, 1.96 ~ 14.08; p < 0.001) and increases in aluminum level (OR, 39.34; CI, 8.20 ~ 89.45; p < 0.001) in children with ASD compared to the control group. The area under the curve (AUC) values of 0.85 for Se, 0.98 for Al, and 0.7 for Zn showed high sensitivity and specificity for all parameters. Results indicate a strong positive connection between ASD and their levels of selenium (Se) and zinc (Zn) (β, 0.48; CI, 0.280 ~ 0.679; p < 0.001 and β, 0.31; CI, 0.10 ~ 0.52; p = 0.005). There is a negative correlation between ASD and aluminum (Al) (β 0.83; CI, 0.71 ~ 0.95; p < 0.001). This element may be a biomarker for autism in youngsters. High odds ratio (OR) values indicate trace element risk in autistic children.

The purpose of this study was to understand caregivers' experience of participating in a caregiver-mediated in-home feeding intervention, the Engaged Eaters Program, for their young autistic child. This qualitative study utilized a thematic approach to analyze post-intervention semi-structured interviews with thirteen mothers of autistic children between the ages of 2 to 7 years after they participated in the intervention. Interview questions focused on the child and family experience, what worked well, what could be improved, and how the intervention integrated into family routines. Four major themes were identified: In-Home Intervention, Parent Skill and Knowledge, Increased Social Participation, and Parent Responsibilities and Challenges. Sub-themes provided descriptions of learning practical tools to support their child, increasing self-efficacy, and impacts on family life. Mothers described an increase in tangible skills that were easily practiced in the home environment that improved their confidence and self-efficacy in feeding their children. They also described how participation did require more work and time commitment for them beyond their regular responsibilities. The caregiver experience is essential to understand for intervention effectiveness while simultaneously addressing child, caregiver, and family needs. By focusing on the mothers' experiences, individualized needs, and self-efficacy, we were able to better understand how integrating an intervention into the family context and daily routines may be beneficial for the whole family.

Alteration of the oral microbiome could potentially play a role in the etiology of certain patients with Autism Spectrum Disorder (ASD), similar to the established link between gut microbiota dysbiosis and ASD. Most studies have assessed oral microbiota in children only and few have explored the oral flora composition in adults with ASD.

In our study, periodontal and dental status was evaluated in 30 adults with ASD using appropriate indices. Oral microbiota samples were collected in crevicular fluid and supra-gingival plaque at inflamed sites in each patient and analyzed using PCR for bacteria and qPCR for protozoa. Demographic data, co-morbidities, medication and oral hygiene habits were also collected.

A total of 86.7% of the patients recruited suffering from severe ASD had periodontal disease and 67% had a high level of supra-gingival plaque. Two major periodontopathogens belonging to the red complex, Treponema denticola and Tannerella forsythia, were both detected in the supra-gingival plaque of 86.2% of patients and in the gingival crevicular fluid of 80 and 86.7% of patients, respectively. Certain microorganisms were statistically more frequently detected in patients with digestive disorders and taking certain medications.

The oral microbiota composition of the adults with ASD showed significant differences compared to neurotypical individuals, particularly in the prevalence of the specific microorganisms P. gingivalis, T. tenax and E. gingivalis ST1. The detection frequency of periodontitis and periodontopathogens may have been underestimated due to the lack of cooperation of the adults with ASD during clinical examination and microbiota sampling. Further studies on larger cohorts are needed to consolidate these results to gain a better understanding of variations in oral microbiota.

This study aimed to evaluate a clinical project aiming to address gaps in healthcare for young children in an immigrant, low-resource district from early identification of regulatory problems, autism, and other neurodevelopmental symptoms by child health services to assessment and interventions in specialist care.

A mixed-model design was employed, consisting of a description of the clinical project and data from healthcare statistics to evaluating the care chain. Qualitative in-depth interviews were conducted to capture the perspectives of participating child health nurses. Data were analyzed using content analysis.

The mean age for referral from primary to specialist care for suspected autism decreased from 38 to 27 months at (n = 59). A total of 55 children were diagnosed with autism. The mean age at autism diagnosis decreased from 44 to 31 months. Waiting times from referral to intervention were shortened. Interventions were already initiated in primary care at the time of referral. Qualitative analyses of nurse experiences revealed three main categories: (1) new and increased knowledge, (2) great importance for every child and family, and (3) an efficient method with fewer gaps, which holds further potential for development.

Professionals' increased knowledge of early symptoms in children, combined with novel healthcare methods for close collaboration, made it possible to bridge the gaps and provide young children and their families with early assessments and essential early interventions. The study results point to opportunities for integrated healthcare and collaboration with families and preschools.

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders with unknown etiology and unclear pathogenesis. Although construction of animal models of ASD using chemical exposure during pregnancy is a mature technique, the gut microbiota of these exposure models induced using different chemicals in mice have not been compared.

To compare the effects of exposure to different chemicals during pregnancy on the composition of gut microbiota in offspring, we treated Institute of Cancer Research (ICR) mice with lipopolysaccharide (LPS) and valproic acid (VPA) during pregnancy to construct different offspring ASD mouse models. After successful model construction, the gut microbiota of these models were studied.

After adjusting for the random effects of the litter, the two groups showed a significant reduction in social time (social deficits) and an increase in self-grooming behaviors (repetitive and stereotyped behaviors). Gut microbiota analysis revealed significant changes, mostly a decrease, in the abundance of four phyla, 52 genera, and 41 species in the two types of ASD models. Several different gut microbes could be related to the development of ASD.

Chemicals exposure during pregnancy induces ASD-related behavioral abnormalities in offspring mice. Importantly, exposure to different chemicals during pregnancy produces varying degrees of effects on gut microbiota composition in offspring ASD models. This finding can provide a reference for studies on the etiology and pathogenesis of ASD.

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.

Gastrointestinal (GI) symptoms are a common comorbidity in children and adolescents with autism spectrum disorder (ASD). Little is known about the impact that GI symptoms have on parental well-being. Parents of 409 children and adolescents with ASD completed the GI Symptoms Inventory, Parenting Stress Index-Short Form, World Health Organization Quality of Life Abbreviated Version, Hospital Anxiety and Depression Scale, and the Multidimensional Scale of Perceived Social Support. High levels of stress were demonstrated by parents with 40.1% receiving clinically significant scores. A relationship was found between parental stress and GI symptoms. Parental anxiety and depression were found at high levels but were not more common in parents of individuals with GI symptoms than those without. Lower levels of quality of life were found in parents of individuals with GI symptoms compared to parents of individuals without GI symptoms. Parents of children with GI symptoms were less satisfied with their personal and social relationships with others. Parents of children with GI symptoms had lower scores on a measure of perceived social support than parents of children and adolescents without GI symptoms. GI symptoms are stressful for parents and future research is needed to determine how to alleviate this stress and to improve the quality of life of parents of individuals with ASD.

Feeding challenges are common for autistic children. Currently, research and intervention for feeding challenges focuses on single factors (e.g. behavior or sensory). Research is needed to understand the complexity of feeding challenges. This study provides a comprehensive description of feeding challenges. Furthermore, this study identifies what factors predict the severity and type of feeding challenges experienced by autistic children. Using the Survey for Characterization of Feeding Challenges in Autistic Children-United States, 427 caregivers of autistic children provided information about their child's feeding challenges. Children were between the ages of 2 and 12 with an average age of 8.42 years. Children in the study had a wide variety of feeding difficulties including challenges in early childhood, sensory challenges, difficulty with family mealtime, and variable self-help skills. On average children's feeding challenges were present prior to their autism diagnosis. We found that children who had early feeding challenges had more severe feeding challenges in later childhood. Also, specific early feeding challenges predicted the types of feeding challenges children would have later in childhood. For example, children who had difficulty transitioning to table foods and who continued to restrict their diet over time were more likely to have sensory-based feeding challenges. Results from this study show how feeding challenges present in a wide variety of ways for autistic children. The findings also highlight the importance of screening for feeding challenges in early childhood and collaborating with families to understand individualized feeding challenge experiences. These results could be used to inform evaluation and intervention for feeding.

This study aimed to characterize aggressive behaviors in autistic youths and to identify the social environment variables most strongly linked with aggression in this clinical population. Participants were 2142 caregivers of autistic youths (ages 6.0-17.9) recruited from autism research centers across the United States. Caregivers completed self-report and behavior rating inventories that assessed both verbal and physical aggression as well as characteristics of the individual youths (sleep quality, gastrointestinal [GI] symptoms, and autism characteristics) and their families (caregiver stress, global family functioning, and sibling relations), peers (emotional bonding, number of friends), schools (academic functioning), and neighborhoods (perceived community safety). We used descriptive analyses to identify which aggressive acts were most common among autistic youths, and we performed bivariate correlations and multiple linear regression analyses to determine which characteristics of the youths and their social environments were most strongly linked with youth aggression. Verbally aggressive youth behaviors were endorsed by caregivers most frequently. Youth age and sex were not associated with verbal or physical aggression. A combination of youth and social environment characteristics accounted for 42.6% of the variance in verbal aggression and 26.0% of the variance in physical aggression. Thus, those characteristics most strongly linked with verbal and physical aggression were strained sibling relations, caregiver stress, youth sleep problems, and youth repetitive and restrictive behaviors. Viewed together, the results suggest that aggressive behaviors in autistic youths are associated with multiple characteristics pertaining to the individual youths and their immediate social environments. Implications for treatment and research are discussed.

The prevalence of autism spectrum disorder (ASD) has increased over the last decade. In this regard, many emerging therapies have been described as ASD therapies. Although ASD does not have a cure, there are several management options available that can help reduce symptom severity. ASD is highly variable and, therefore, standard treatment protocols and studies are challenging to perform. Many of these therapies also address comorbidities for which patients with ASD have an increased risk. These concurrent diagnoses can include psychiatric and neurological disorders, including attention deficit and hyperactivity disorder, anxiety disorders, and epilepsy, as well as gastrointestinal symptoms such as chronic constipation and diarrhea. Both the extensive list of ASD-associated disorders and adverse effects from commonly prescribed medications for patients with ASD can impact presenting symptomatology. It is important to keep these potential interactions in mind when considering additional drug treatments or complementary therapies. This review addresses current literature involving novel pharmacological treatments such as oxytocin, bumetanide, acetylcholinesterase inhibitors, and memantine. It also discusses additional therapies such as diet intervention, acupuncture, music therapy, melatonin, and the use of technology to aid education. Notably, several of these therapies require more long-term research to determine efficacy in specific ASD groups within this patient population.

Investigate the association between gastrointestinal (GI) issues and psychometric scores among children with developmental delays and typical development. We examined the association between GI issues and the Mullen Scale of Early Learning (MSEL), Vineland Adaptive Behavior Subscales (VABS), and Aberrant Behavior Checklist (ABC) scores from participants with autism spectrum disorder (ASD), Down syndrome (DS), other developmental delays (DD) and typical development (TD) from the CHildhood Autism Risk from Genetics and Environment (CHARGE) Study (n = 1603). Approximately 32% of children with ASD, 31% of children with DD, and 20% of children with DS reported at least one GI issue, compared to 7% of TD controls. Constipation was the most frequently reported symptom for the entire population, including controls. In general, GI issues correlated with poorer behavioral scores (decreased communication, daily living, socialization, and motor skills on the VABS, and increased irritability/agitation, lethargy/social withdrawal, stereotypic behavior, and hyperactivity/noncompliance on the ABC) among ASD cases. Analysis by sex indicated that GI issues also correlated with poorer cognitive scores (fine motor, receptive language, expressive language, and MSEL composite scores), and adaptive behavior (communication skills, daily living skills, motor, and VABS composite scores) among boys with DD, but not girls with DD-suggesting sex differences among DD cases. Even TD controls showed increased stereotypic behavior and social withdrawal in association with GI issues. However, GI issues were not correlated with impairments in psychometric scores among DS cases. Given that GI issues correlate with deficits in behavioral and cognitive scores, future studies should investigate the treatment of GI symptoms in children with ASD and DD.

The gut-brain axis is evident in modulating neuropsychiatric diseases including autism spectrum disorder (ASD). Chromosomal 16p11.2 microduplication 16p11.2dp/+ is among the most prevalent genetic copy number variations (CNV) linked with ASD. However, the implications of gut microbiota status underlying the development of ASD-like impairments induced by 16p11.2dp/+ remains unclear. To address this, we initially investigated a mouse model of 16p11.2dp/+, which exhibits social novelty deficit and repetitive behavior characteristic of ASD. Subsequently, we conducted a comparative analysis of the gut microbial community and metabolomic profiles between 16p11.2dp/+ and their wild-type counterparts using 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC/MS). Our microbiota analysis revealed structural dysbiosis in 16p11.2dp/+ mice, characterized by reduced biodiversity and alterations in species abundance, as indicated by α/β-diversity analysis. Specifically, we observed reduced relative abundances of Faecalibaculum and Romboutsia, accompanied by an increase in Turicibacter and Prevotellaceae UCG_001 in 16p11.2dp/+ group. Metabolomic analysis identified 19 significantly altered metabolites and unveiled enriched amino acid metabolism pathways. Notably, a disruption in the predominantly histamine-centered neurotransmitter network was observed in 16p11.2dp/+ mice. Collectively, our findings delineate potential alterations and correlations among the gut microbiota and microbial neurotransmitters in 16p11.2dp/+ mice, providing new insights into the pathogenesis of and treatment for 16p11.2 CNV-associated ASD.

Background and Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by challenges in communication, social interactions, and repetitive behaviors. Although the factors that influence the development of this condition are unknown, certain chemical compounds such as pesticides have been proposed as possible contributors. Due to the lack of an established causal link between pesticide exposure and ASD, this study aimed to evaluate this potential association. Materials and Methods: A case-control study was carried out to ascertain the prevalence and risk associated with ASD in relation to pesticide exposure over a 21-year study period (2000-2021). Results: We included 2821 individuals diagnosed with ASD residing in areas of both high and low pesticide exposure in southern Spain. There was a rise in the ASD prevalence rate in regions with elevated pesticide use when compared to regions with low use [odds ratio (OR): 1.34, 95% confidence interval (CI), (1.24-1.44)]. Notably, men had the highest likelihood, with an OR: 1.42, 95% CI, (1.30-1.55). Furthermore, after performing multiple binary logistic regression adjusted for age, sex, and geographical area, males exhibited a higher likelihood compared to females [OR: 2.41, 95% CI, (2.21-2.62)]. Conclusions: Overall, this research suggests a connection between heightened environmental pesticide exposure due to increased agricultural use and autism.

Eating behavior, which includes eating habits and preferences, frequency of eating, and other features related to diet, is a major characteristic not only of a person's nutritional status, but also of health in general. In recent years, the prevalence of eating disorders in children has tended to increase; they also require cross-system approaches in diagnosis by a variety of specialists and correction requires appropriate selection of optimal methods. Maladaptive eating attitudes formed at an early age can contribute to the formation of eating disorders, which can lead to or worsen various neuropsychiatric diseases, digestive diseases, and other related conditions. In children with autism spectrum disorder (ASD), eating disorders often appear earlier than other major symptoms of the condition. However, the clinical manifestations of eating disorders in children with ASD are varied and differ in severity and duration, whereas these disorders in neurotypical children might present as short-lived and may not lead to serious consequences. Nevertheless, cases of progressive eating disorders accompanied by a child presenting as under- or overweight and/or with macronutrient and micronutrient deficiencies cannot be excluded. Given the high prevalence of eating disorders in children, many researchers have highlighted the lack of a valid and universally accepted instruments to assess atypical eating behaviors in this population. Therefore, in this review, we wanted to highlight the problems and causes of eating disorders in children, and also to analyze the existing approaches to the validation of these problems, taking into account the existing behavioral features in children with ASD.

There is increasing evidence that alterations in gut microbiota (GM) composition are associated with autism spectrum disorder (ASD), but no reliable causal relationship has been established. Therefore, a 2-sample Mendelian randomization (MR) study was conducted to reveal a potential causal relationship between GM and ASD. Instrumental variables for 211 GM taxa were obtained from genome-wide association studies (GWAS) and Mendelian randomization studies to estimate their impact on ASD risk in the iPSYCH-PGC GWAS dataset (18,382 ASD cases and 27,969 controls). Inverse variance weighted (IVW) is the primary method for causality analysis, and several sensitivity analyses validate MR results. Among 211 GM taxa, IVW results confirmed that Tenericutes (P value = .0369), Mollicutes (P value = .0369), Negativicutes (P value = .0374), Bifidobacteriales (P value = .0389), Selenomonadales (P value = .0374), Bifidobacteriaceae (P value = .0389), Family XIII (P value = .0149), Prevotella7 (P value = .0215), Ruminococcaceae NK4A214 group (P value = .0205) were potential protective factors for ASD. Eisenbergiella (P value = .0159) was a possible risk factor for ASD. No evidence of heterogeneous, pleiotropic, or outlier single-nucleotide polymorphism was detected. Additionally, further sensitivity analysis verified the robustness of the above results. We confirm a potential causal relationship between certain gut microbes and ASD, providing new insights into how gut microbes mediate ASD. The association between them needs to be further explored and will provide new ideas for the prevention and treatment of ASD.

Autism spectrum disorders (ASDs) are recognized as central neurodevelopmental disorders diagnosed by impairments in social interactions, communication and repetitive behaviours. The recognition of ASD as a central nervous system (CNS)-mediated neurobehavioural disorder has led most of the research in ASD to be focused on the CNS. However, gastrointestinal function is also likely to be affected owing to the neural mechanistic nature of ASD and the nervous system in the gastrointestinal tract (enteric nervous system). Thus, it is unsurprising that gastrointestinal disorders, particularly constipation, diarrhoea and abdominal pain, are highly comorbid in individuals with ASD. Gastrointestinal problems have also been repeatedly associated with increased severity of the core symptoms diagnostic of ASD and other centrally mediated comorbid conditions, including psychiatric issues, irritability, rigid-compulsive behaviours and aggression. Despite the high prevalence of gastrointestinal dysfunction in ASD and its associated behavioural comorbidities, the specific links between these two conditions have not been clearly delineated, and current data linking ASD to gastrointestinal dysfunction have not been extensively reviewed. This Review outlines the established and emerging clinical and preclinical evidence that emphasizes the gut as a novel mechanistic and potential therapeutic target for individuals with ASD.

The association between gut microbiota and central nervous system (CNS) development has garnered significant research attention in recent years. Evidence suggests bidirectional communication between the CNS and gut microbiota through the brain-gut axis. As a long and complex process, CNS development is highly susceptible to both endogenous and exogenous factors. The gut microbiota impacts the CNS by regulating neurogenesis, myelination, glial cell function, synaptic pruning, and blood-brain barrier permeability, with implication in various CNS disorders. This review outlines the relationship between gut microbiota and stages of CNS development (prenatal and postnatal), emphasizing the integral role of gut microbes. Furthermore, the review explores the implications of gut microbiota in neurodevelopmental disorders, such as autism spectrum disorder, Rett syndrome, and Angelman syndrome, offering insights into early detection, prompt intervention, and innovative treatments.

Gastrointestinal symptoms and inflammatory gastrointestinal diseases exist at higher rates in the autistic population. It is not clear however whether autism is associated with elevated gastrointestinal inflammation as studies examining non-invasive faecal biomarkers report conflicting findings. To understand the research landscape and identify gaps, we performed a systematic review and meta-analysis of studies measuring non-invasive markers of gastrointestinal inflammation in autistic and non-autistic samples. Our examination focused on faecal biomarkers as sampling is non-invasive and these markers are a direct reflection of inflammatory processes in the gastrointestinal tract.

We extracted data from case-control studies examining faecal markers of gastrointestinal inflammation. We searched PubMed, Embase, Cochrane CENTRAL, CINAHL, PsycINFO, Web of Science Core Collection and Epistemonikos and forward and backwards citations of included studies published up to April 14, 2023 (PROSPERO CRD42022369279).

There were few studies examining faecal markers of gastrointestinal inflammation in the autistic population, and many established markers have not been studied. Meta-analyses of studies examining calprotectin (n = 9) and lactoferrin (n = 3) were carried out. A total of 508 autistic children and adolescents and 397 non-autistic children and adolescents were included in the meta-analysis of calprotectin studies which found no significant group differences (ROM: 1.30 [0.91, 1.86]). Estimated differences in calprotectin were lower in studies with siblings and studies which did not exclude non-autistic controls with gastrointestinal symptoms. A total of 139 autistic participants and 75 non-autistic controls were included in the meta-analysis of lactoferrin studies which found no significant group differences (ROM: 1.27 [0.79, 2.04]).

All studies included in this systematic review and meta-analysis examined children and adolescents. Many studies included non-autistic controls with gastrointestinal symptoms which limit the validity of their findings. The majority of studies of gastrointestinal inflammation focused on children under 12 with few studies including adolescent participants. Most studies that included participants aged four or under did not account for the impact of age on calprotectin levels. Future studies should screen for relevant confounders, include larger samples and explore gastrointestinal inflammation in autistic adolescents and adults.

There is no evidence to suggest higher levels of gastrointestinal inflammation as measured by calprotectin and lactoferrin are present in autistic children and adolescents at the population level. Preliminary evidence suggests however that higher calprotectin levels may be present in a subset of autistic participants, who may be clinically characterised by more severe gastrointestinal symptoms and higher levels of autistic traits.

Since the early 1990s, there have literally been thousands of reports related to magnetic resonance imaging of the autistic brain. The goals of these studies have ranged from identifying the earliest biological predictors of an autistic diagnosis to determining brain systems most altered in autistic individuals. Some of the later works attempt to use distinct patterns of brain alterations to help define more homogenous subtypes of autism. Far less work has been done to identify brain changes that are associated with therapeutic interventions. In this chapter, we will touch on all of these efforts as they relate to the general topic of the usefulness of brain imaging as a biomarker of autism.

The mammalian gut contains a community of microorganisms called gut microbiome. The gut microbiome is integrated into mammalian physiology, contributing to metabolism, production of metabolites, and promoting immunomodulatory actions. Microglia, the brain's resident innate immune cells, play an essential role in homeostatic neurogenesis, synaptic remodeling, and glial maturation. Microglial dysfunction has been implicated in the pathogenesis of several neuropsychiatric disorders. Recent findings indicate that microglia are influenced by the gut microbiome and their derived metabolites throughout life. The pathways by which microbiota regulate microglia have only started to be understood, but this discovery has the potential to provide valuable insights into the pathogenesis of brain disorders associated with an altered microbiome. Here, we discuss the recent literature on the role of the gut microbiome in modulating microglia during development and adulthood and summarize the key findings on this bidirectional crosstalk in selected examples of neuropsychiatric and neurodegenerative disorders. We also highlight some current caveats and perspectives for the field.

Individuals with Down syndrome (DS) experience a range of medical and neurodevelopmental conditions, necessitating systematic study of their occurrence and impact on neurodevelopmental outcomes. We describe the prevalence and relationships of medical, neurodevelopmental (ND), and mental health (MH) conditions in children with DS. We created a prospective clinical database of individuals with DS, integrated into the workflow of a specialty Down Syndrome Program at a specialty pediatric referral hospital. Conditions were collected through caregiver- and clinician report at clinical visits (N = 599). We calculated frequencies of medical, ND, and MH conditions and then assessed the relationship between medical, ND, and MH conditions using frequencies and comparative statistics. The most frequent co-occurring conditions were vision (72.5%), ear/hearing (71.0%), gastrointestinal (61.3%), respiratory (45.6%), and feeding (33.6%) problems, with variation in frequency by age. ND and MH conditions were reported in one quarter, most commonly autism spectrum disorder and attention-deficit/hyperactivity disorder. Those with ND and MH conditions had greater frequency of medical conditions, with highest rates of vision, ear/hearing, and gastrointestinal issues, and CHD. Systematically collected clinical data in a large cohort of children with DS reveals high prevalence of several co-occurring medical, ND, and MH conditions. Clinical care requires an understanding of the complex relationship between medical conditions and neurodevelopment.

Alteration of the microbiota-gut-brain axis has been recently recognized as a possible contributor to the physiopathology of autism spectrum disorder (ASD). In this context, microRNA (miRNAs) dysfunction, implicated both in several neuropathological conditions including ASD and in different gastrointestinal disorders (GIDs), could represent an important modulating factor. In this contextual framework, we studied the transcriptional profile of specific circulating miRNAs associated with both ASD (miR-197-5p, miR-424-5p, miR-500a-5p, miR-664a-5p) and GID (miR-21-5p, miR-320a-5p, miR-31-5p, miR-223-5p) in a group of pre-schoolers with ASD and in typically developing (TD) peers. In the ASD group, we also assessed the same miRNAs after a 6-month supplementation with probiotics and their correlation with plasma levels of zonulin and lactoferrin. At baseline, the expression of miRNAs involved in ASD were significantly reduced in ASD pre-schoolers vs. TD controls. Regarding the miRNAs involved in GID, the expression levels of miR-320-5p, miR-31-5p, and miR-223-5p were significantly higher in ASD than in TD subjects, whereas miR-21-5p showed significantly reduced expression in the ASD group vs. TD group. Supplementation with probiotics did not significantly change the expression of miRNAs in the ASD population. We found a significative negative correlation between zonulin and miR-197-5p and miR-21-5p at baseline, as well as between lactoferrin and miR-223-5p after 6 months of probiotic supplementation. Our study confirms the presence of an altered profile of the miRNAs investigated in ASD versus TD peers that was not modified by supplementation with probiotics.

Gastrointestinal (GI) symptoms are highly prevalent among individuals with autism spectrum disorder (ASD), but the molecular link between ASD and GI dysfunction remains poorly understood. The enteric nervous system (ENS) is critical for normal GI motility and has been shown to be altered in mouse models of ASD and other neurological disorders. Contactin-associated protein-like 2 (Cntnap2) is an ASD-related synaptic cell-adhesion molecule important for sensory processing. In this study, we examine the role of Cntnap2 in GI motility by characterizing Cntnap2's expression in the ENS and assessing GI function in Cntnap2 mutant mice. We find Cntnap2 expression predominately in enteric sensory neurons. We further assess in vivo and ex vivo GI motility in Cntnap2 mutants and show altered transit time and colonic motility patterns. The overall organization of the ENS appears undisturbed. Our results suggest that Cntnap2 plays a role in GI function and may provide a molecular link between ASD and GI dysfunction.

Many youth with autism spectrum disorder (ASD) experience co-occurring conditions, such as gastrointestinal (GI) problems and internalizing symptoms. However, the relationship among these co-occurring problems is not well-understood. We analyzed parent reports of GI problems and internalizing symptoms of 621 youth with ASD using path models in a structural equation modeling framework. The best-fitting model was a bidirectional model wherein internalizing symptoms, including withdrawn and anxious behavior, were correlated with GI problems, including constipation, diarrhea, nausea, and stomach pain. This study provides a better understanding of the relationship among co-occurring conditions in youth with ASD and should encourage clinicians to consider treatment of underlying internalizing symptoms or GI problems when providing services for individuals with ASD.

Fragile X syndrome (FXS) is the leading known monogenetic cause of autism with an estimated 21-50% of FXS individuals meeting autism diagnostic criteria. A critical gap in medical care for persons with autism is an understanding of how environmental exposures and gene-environment interactions affect disease outcomes. Our research indicates more severe neurological and metabolic outcomes (seizures, autism, increased body weight) in mouse and human models of autism spectrum disorders (ASD) as a function of diet. Thus, early-life exposure to chemicals in the diet could cause or exacerbate disease outcomes. Herein, we review the effects of potential dietary toxins, i.e., soy phytoestrogens, glyphosate, and polychlorinated biphenyls (PCB) in FXS and other autism models. The rationale is that potentially toxic chemicals in the diet, particularly infant formula, could contribute to the development and/or severity of ASD and that further study in this area has potential to improve ASD outcomes through dietary modification.

Gastrointestinal (GI) symptoms are highly prevalent among individuals with autism spectrum disorder (ASD), but the molecular link between ASD and GI dysfunction remains poorly understood. The enteric nervous system (ENS) is critical for normal GI motility and has been shown to be altered in mouse models of ASD and other neurological disorders. Contactin-associated protein-like 2 (Cntnap2) is an ASD-related synaptic cell-adhesion molecule important for sensory processing. In this study, we examine the role of Cntnap2 in GI motility by characterizing Cntnap2's expression in the ENS and assessing GI function in Cntnap2 mutant mice. We find Cntnap2 expression predominately in enteric sensory neurons. We further assess in-vivo and ex-vivo GI motility in Cntnap2 mutants and show altered transit time and colonic motility patterns. The overall organization of the ENS appears undisturbed. Our results suggest that Cntnap2 plays a role in GI function and may provide a molecular link between ASD and GI dysfunction.

Individuals with Autism Spectrum Disorder (ASD; autism) commonly present with gastrointestinal (GI) illness in addition to core diagnostic behavioural traits. The appendix, or cecum in mice, is important for GI homeostasis via its function as a key site for fermentation and a microbial reservoir. Even so, the role of the appendix and cecum in autism-associated GI symptoms remains uninvestigated. Here, we studied mice with an autism-associated missense mutation in the post-synaptic protein neuroligin-3 (Nlgn3R451C), which impacts brain and enteric neuronal activity. We assessed for changes in cecal motility using a tri-cannulation video-imaging approach in ex vivo preparations from wild-type and Nlgn3R451C mice. We investigated cecal permeability and neurally-evoked secretion in wild-type and Nlgn3R451C tissues using an Ussing chamber set-up. The number of cecal patches in fresh tissue samples were assessed and key immune populations including gut macrophages and dendritic cells were visualised using immunofluorescence. Nlgn3R451C mice displayed accelerated cecal motor complexes and reduced cecal weight in comparison to wildtype littermates. Nlgn3R451C mice also demonstrated reduced neurally-evoked cecal secretion in response to the nicotinic acetylcholine receptor agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP), but permeability was unchanged. We observed an increase in the number of cecal patches in Nlgn3R451C mice, however the cellular morphologies of key immune populations studied were not significantly altered. We show that the R451C nervous system mutation leads to cecal dysmotility, impaired secretion, and neuro-immune alterations. Together, these results suggest that the R451C mutation disrupts the gut-brain axis with GI dysfunction in autism.

Gastrointestinal symptoms (GI) are very common among individuals on the autism spectrum. Prior research reports mixed findings regarding whether individuals with autism and co-occurring intellectual disability (ID) have elevated risk of gastrointestinal symptoms relative to individuals with autism alone. GI symptoms can be challenging to assess in individuals with autism spectrum disorder (ASD) and/or ID given challenges with language, communication, and interoception. Prior research has tended to only include individuals with documented presence or absence of GI symptoms or conditions, that is, to exclude observations in which there is uncertainty regarding presence of GI symptoms. Therefore, none of the prior autism studies reported the association between ID and the certainty regarding presence or absence of GI symptoms. The objective of this study was to examine differences in parental certainty and odds of reporting gastrointestinal signs and symptoms among children on the autism spectrum, with and without intellectual disability. Participants were 308 children (36% ID) with a clinical diagnosis of autism spectrum disorder (6-17 years). Parents endorsed whether their child had experienced or displayed a range of signs or symptoms related to GI problems in the past 3 months. Parents of autistic children with ID were less certain about the presence of more subjective symptoms, including abdominal pain, nausea, and bloating. Conversely, certainty regarding more objective signs (e.g., constipation, diarrhea, spitting up, etc.) was not significantly different. More accurate measures for GI signs/symptoms are needed for this population.

Gastrointestinal (GI) symptoms are frequently experienced by children with autism spectrum disorder (ASD), and these symptoms cause difficulties for these children and their families. However, studies of GI symptom prevalence differ significantly. This meta-analysis aimed to analyze the prevalence of GI symptoms in children with ASD.

PubMed, Scopus, Web of Science, EMBASE were electronically searched to collect all literature on gastrointestinal symptoms of children with ASD collected through questionnaires or scales from January 2012 to May 2021. Four researchers independently scanned the literature and extracted information on general characteristics. First author name, year of publication, geographical location, type of study, sample sizes of ASD and control (if any) children, sex and average age, number of GI cases, number of GI symptoms, GI assessment tools (gastrointestinal symptoms scale), autism diagnosis methods, and other necessary data were collected and analyzed using Stata V16. The questionnaires included the Rome, 6-GSI, GIQ, GSRS, GSIQ, ADI-R, PedsQL-GI, parent-report, GI-related, and self-administered questionnaires. Compared with typically developing (TD) children, the odds ratio for In children with ASD with at least one GI symptom was 3.64, and the total prevalence was 55%. The cumulative prevalence rates of various symptoms were summarized, showing that 37% of children with ASD had constipation, 21% had abdominal pain, 19% had diarrhea, 8% had vomiting, and 23% had abdominal distension.

The results of this meta-analysis on GI symptoms in ASD show that patients with ASD are more likely to develop symptoms than TD children. The prevalence of GI symptoms in In children with ASD was 55%.

www.crd.york.ac.uk/PROSPERO, identifier, #CRD42017080579.

Autism spectrum disorder (ASD) includes a range of multifactorial neurodevelopmental disabilities characterized by a variable set of neuropsychiatric symptoms. Immunological abnormalities have been considered to play important roles in the pathogenesis of ASD, but it is still unknown which abnormalities are more prominent.

A total of 105 children with ASD and 105 age and gender-matched typically developing (TD) children were recruited. An eating and mealtime behavior questionnaire, dietary habits, and the Bristol Stool Scale were investigated. The immune cell profiles in peripheral blood were analyzed by flow cytometry, and cytokines (IFN-γ, IL-8, IL-10, IL-17A, and TNF-α) in plasma were examined by Luminex assay. The obtained results were further validated using an external validation cohort including 82 children with ASD and 51 TD children.

Compared to TD children, children with ASD had significant eating and mealtime behavioral changes and gastrointestinal symptoms characterized by increased food fussiness and emotional eating, decreased fruit and vegetable consumption, and increased stool astriction. The proportion of γδT cells was significantly higher in children with ASD than TD children (β: 0.156; 95% CI: 0.888 ∼ 2.135, p < 0.001) even after adjusting for gender, eating and mealtime behaviors, and dietary habits. In addition, the increased γδT cells were evident in all age groups (age < 48 months: β: 0.288; 95% CI: 0.420 ∼ 4.899, p = 0.020; age ≥ 48 months: β: 0.458; 95% CI: 0.694 ∼ 9.352, p = 0.024), as well as in boys (β: 0.174; 95% CI: 0.834 ∼ 2.625, p < 0.001) but not in girls. These findings were also confirmed by an external validation cohort. Furthermore, IL-17, but not IFN-γ, secretion by the circulating γδT cells was increased in ASD children. Machine learning revealed that the area under the curve in nomogram plots for increased γδT cells combined with eating behavior/dietary factors was 0.905, which held true in both boys and girls and in all the age groups of ASD children. The decision curves showed that children can receive significantly higher diagnostic benefit within the threshold probability range from 0 to 1.0 in the nomogram model.

Children with ASD present with divergent eating and mealtime behaviors and dietary habits as well as gastrointestinal symptoms. In peripheral blood, γδT cells but not αβT cells are associated with ASD. The increased γδT cells combined with eating and mealtime behavior/dietary factors have a high value for assisting in the diagnosis of ASD.

Autism spectrum disorder (ASD) is classified as a neurodevelopmental disorder. The Diagnostic and Statistical Manual of Mental Disorders (DSM)-V, which first described ASD, lists persistent deficits in social communication and interrelationships, as well as limited and recurrent modes of behavior, interests, and activities as diagnostic items. Until recently, understanding the pathophysiology of ASD has been mostly from a neurophysiological perspective, and interventions have been mostly behavioral and psychological. In recent years, however, it has become clear that ASD also affects many bodily systems, including the immune system, the sensorimotor system, and the gut-brain axis, and that these factors simultaneously influence it. In light of this background, a new "connectivome theory" has been proposed as a hypothesis for understanding ASD. "Exercise," "nutrition," and "sleep," which are discussed in this mini-review, have a particularly strong relationship with the immune, musculoskeletal, and gut systems among the pathologies mentioned in the "connectivome theory," furthermore, many reports suggest improvements in stereo-responsive behavior and social and communication skills, which are the core symptoms of ASD. In addition, these interventions are characterized by being less subject to location and cost limitations and excel in the continuity of therapeutic intervention, and the three interventions may have a reciprocal positive impact and may function as three pillars to support ASD.

This study examined the relationship between sensory processing (SP) differences and behavioral problems in children with autism spectrum disorder (ASD). We also investigated whether audiological test results could objectively detect auditory processing differences.

Forty-six children with ASD, ages 3-9 years, were enrolled in the study. Problematic behaviors and sensory processing of children were assessed using scales. The otolaryngologist performed a detailed head and neck examination and a formal audiological examination was performed by an audiologist.

Stereotypy, hyperactivity, and irritability were related to sensation seeking. Stereotypy was also associated with visual processing. Touch processing differences was related to irritability and inappropriate speech. Lethargy was associated with auditory processing. There were no differences in SP and behavior problems in the children whose audiological profiles could be measured between those who passed or failed the test.

There was an association between SP differences and behavioral problems in children with ASD, supporting previous studies. Audiological test results did not reveal the SP differences documented in the parent forms.

Neuroplasticity refers to the ability of brain circuits to reorganize and change the properties of the network, resulting in alterations in brain function and behavior. It is traditionally believed that neuroplasticity is influenced by external stimuli, learning, and experience. Intriguingly, there is new evidence suggesting that endogenous signals from the body's periphery may play a role. The gut microbiota, a diverse community of microorganisms living in harmony with their host, may be able to influence plasticity through its modulation of the gut-brain axis. Interestingly, the maturation of the gut microbiota coincides with critical periods of neurodevelopment, during which neural circuits are highly plastic and potentially vulnerable. As such, dysbiosis (an imbalance in the gut microbiota composition) during early life may contribute to the disruption of normal developmental trajectories, leading to neurodevelopmental disorders. This review aims to examine the ways in which the gut microbiota can affect neuroplasticity. It will also discuss recent research linking gastrointestinal issues and bacterial dysbiosis to various neurodevelopmental disorders and their potential impact on neurological outcomes.

Autism spectrum disorder (AU) is present in approximately 2% of the population and is often associated with co-morbidities that can impact quality of life. One of the most common co-morbidities in autism is the presence of gastrointestinal (GI) symptoms consisting of irregular bowel habits such as constipation, diarrhea, or alternating bowel habit. Evidence of immune infiltration and immune activation has been shown in the ileum and colon of children with AU with GI symptoms. Moreover, immune dysfunction is a contributing factor in many GI diseases, and we hypothesize that it would be more apparent in children with AU that exhibit GI symptoms than those who do not present with GI symptoms. The aim of this preliminary study was to determine whether there are altered cytokine levels in plasma in children with AU with GI symptoms compared with children with AU without GI symptoms, typically developing (TD) children with GI symptoms and TD children without GI symptoms, from the same population-based cohort. Plasma cytokine levels were assessed by multiplex assays. No differences in plasma cytokines were observed in TD controls with or without GI symptoms; however, many innate (IL-1α, TNFα, GM-CSF, IFNα) and adaptive cytokines (IL-4, IL-13, IL-12p70) were increased in AU children with GI symptoms compared with children with AU with no GI symptoms. The mucosal relevant cytokine IL-15 was increased in AU with GI symptoms compared with all groups. In contrast, the regulatory cytokine IL-10, was reduced in AU with GI symptoms and may suggest an imbalance in pro-inflammatory/regulatory signals. These data suggest that children with AU and GI symptoms have an imbalance in their immune response that is evident in their circulating plasma cytokine levels. A finding that could point to potential therapeutic and/or monitoring strategies for GI issues in AU.

The relationship between trace elements and neurological development is an emerging research focus. We performed a case-control study to explore (1) the differences of 13 trace elements chromium (Cr), manganese (Mn), cobalt (Co), zinc (Zn), arsenic (As), selenium (Se), molybdenum (Mo), cadmium (Cd), stannum (Sn), stibium (Sb), mercury (Hg), titanium (TI), and plumbum (Pb) concentration in whole blood and urine between autism spectrum disorder (ASD) children and their typical development peers, and (2) the association between the 13 trace elements and core behaviors of ASD. Thirty ASD subjects (cases) and 30 age-sex-matched healthy subjects from Baise City, Guangxi Zhuang Autonomous Region, China, were recruited. Element analysis was carried out by inductively coupled plasma-optical emission spectrometry. Autistic behaviors were assessed using Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), and Children Neuropsychological and Behavior Scale (CNBS). The whole blood concentrations of Mo (p = 0.004), Cd (0.007), Sn (p = 0.003), and Pb (p = 0.037) were significantly higher in the ASD cases than in the controls. Moreover, Se (0.393), Hg (0.408), and Mn (- 0.373) concentrations were significantly correlated between whole blood and urine levels in ASD case subjects. There were significant correlations between whole blood Sb (0.406), Tl (0.365), Mo (- 0.4237), Mn (- 0.389), Zn (0.476), and Se (0.375) levels and core behaviors of ASD. Although the mechanism of trace element imbalance in ASD is unclear, these data demonstrate that core behaviors of ASD may be affected by certain trace elements. Further studies are recommended for exploring the mechanism of element imbalance and providing corresponding clinical treatment measures.

The aim of this study was to evaluate the interaction between gastrointestinal (GI) disorders, sleep problems, and challenging behaviors in children with a diagnosis of Autism Spectrum Disorder (ASD) and their effect on parental stress. The secondary objective was to assess the frequency and type of GI and feeding disorders in a sample of children with ASD through a multidisciplinary assessment and, finally, to investigate families' perceptions and satisfaction with the proposed multidisciplinary approach. All children underwent a comprehensive gastroenterological and neuropsychiatric evaluation supported by standardized questionnaires. Pediatric gastroenterologists, specifically trained in Applied Behavior Analysis (ABA), provided advice for parent-delivered behavioral intervention for food selectivity. Thirty-six children with an autism diagnosis (29 males, age 4.5 +/-2.2 years, mean +/- SD) were enrolled. A positive correlation between sleep problems and aggressive behavior was found, and this association was stronger in children experiencing more problematic mealtime behaviors (b = 0.788, p = 0.014). Sleep difficulties were associated with stereotyped behaviors and parent-perceived stress. Parents interviewed about the gastroenterology visit perceived this multidisciplinary approach as helpful in addressing food selectivity. This study shows that sleep and mealtime issues can have a synergistic negative impact on ASD symptoms. A multidisciplinary approach and an integrated assessment of GI, feeding problems, and sleep disorders could be helpful in diagnosing comorbidities and to provide targeted advice to parents.

This study aimed to investigate the immediate and continual perturbation to the gut microbiota of offspring in the weeks post-weaning and how these may be modulated by treating pregnant C57BL/6J dams with antibiotics (ABX). We used a broad-spectrum antibiotic cocktail consisting of ampicillin 1 mg/mL, neomycin 1 mg/mL, and vancomycin 0.5 mg/mL, or vancomycin 0.5 mg/mL alone, administered ad-lib orally to dams via drinking water during gestation and stopped after delivery. We analyzed the gut microbiota of offspring, cytokine profiles in circulation, and the brain to determine if there was evidence of a gut-immune-brain connection. Computationally predicted metabolic pathways were calculated from 16s rRNA sequencing data. ABX treatment can negatively affect the gut microbiota, including reduced diversity, altered metabolic activity, and immune function. We show that the maternal ABX-treatment continues to alter the offspring's gut microbiota diversity, composition, and metabolic pathways after weaning, with the most significant differences evident in 5-week-olds as opposed to 4-week-olds. Lower levels of chemokines and inflammatory cytokines, such as interleukin (IL)-1α and IL-2, are also seen in the periphery and brains of offspring, respectively. In conclusion, this study shows maternal antibiotic administration alters gut microbiome profiles in offspring, which undergoes a continuous transformation, from week to week, at an early age after weaning.