A prebiotic intervention study in children with autism spectrum disorders (ASDs)

BACKGROUND: Autism spectrum disorder (ASD) is an early-onset neurodevelopmental disorder with 1 in 68 children prevalence. The key symptoms of ASD include social deficits, verbal and non-verbal communication deficits, and restricted, repetitive patterns of behavior, interests, or activities. For unknown reasons, gastrointestinal symptoms are related to ASD. The aim of the current paper is to review the available literature on dietary interventions in children with ASD and provide up-to-date evidence. METHODS: Searches in online databases, using the search terms’ dietary intervention, “autism spectrum disorders,” and “autism” were conducted. The search targeted publications ranging from 2010 to 2020. RESULTS: Twenty-six studies with different study designs which evaluated the effectiveness of specific dietary interventions in children with ASD were included in our review. Several dietary interventions were of popular practice in the management of children with ASD, including elimination (gluten-/casein-free diet and oligoantigenic diet), modification (modified ketogenic diet), supplementation (minerals, vitamins, omega 3, and omega 6), and exclusion (food additives). Studies showed different results with varying degrees of evidence. Overall, data were inadequate to make accurate conclusions. CONCLUSION: There is little evidence to support the use of dietary interventions for children with ASD. Additional high-quality studies and further research are, therefore, needed.

Human microbiota are colonies of microorganisms located in different parts of the human body with diverse functions. Healthy gut microbiota comprises differing ratios of microoganisms wholly contributing to metabolic and other molecular reactions in a healthy, functioning body. After the demonstration of the bidirectional interaction between the central nervous system and gut microbiota through neuroendocrine, neuroimmune, and autonomic nervous mechanisms, investigations have been started on the microbiota-gut-brain axis in psychiatric disorders. Autism spectrum disorder (ASD), which is a neurodevelopmental disorder of early childhood, is one of these disorders. Most of such studies were cross-sectional and mainly investigated the bacterial species. Changes in gut microbiota composition and the leaky gut syndrome are some of the hypotheses proposed to explain the core symptoms and gastrointestinal (GI) symptoms of ASD. Probiotics, prebiotics, fecal microbiota transplantation, diet have been proposed as treatment options. However, the role of microbiota in diagnosis, followup, and treatment is not yet clear. The bidirectional interaction between central nervous system and intestinal microbiota makes it difficult to establish the cause-effect relationship. The current data on microbiota may be useful to plan patient-specific treatment in autistic children with GI symptoms. This article aims to review the results of the studies on microbiota in animal models and children and discuss the emerging clinical relationship of ASD and gut microbiota.

Gluten-free and casein-free diet is frequently used in the support of therapy of children with autism spectrum disorders. In addition, many parents restrict the consumption of simple sugars for their children. The aim of this paper was to understand factors influencing purchase decision in case of family with children with autism spectrum disorders on gluten-free and/or casein-free and/or sugar-free diet and the difficulties associated with this type of nutrition. The study covered a group of 40 families with children with autism spectrum disorders (32 boys and 8 girls) aged 3 to 10 years. Data were collected with questionnaire included questions concerning overall characteristics of caregivers, availability of foods used in the special diet, factors affecting decision on the purchase of products, difficulties in maintaining the child nutrition method. The factors having strongest impact on parents' decisions on the purchase of products were product composition, presence of a certificate confirming the absence of gluten and/or milk and taste values. Exclusion diet constituted a considerable obstruction for traveling, social gatherings and resulted in conflicts with family and the environment. The limited range of healthy gluten-free, casein-free and sugar-free foods, low taste quality and unsatisfactory quality impeded purchase and preparation of varied meals. The surveyed parents were aware consumers, paying attention primarily to product composition and safety. The respondents were looking for healthy, organic and nutritionally valuable products with low sugar content. Further development of the gluten/casein/ sugar free products market may considerably improve certain aspects of family's life with children with autism spectrum disorders.

Aims and HypothesisWe propose a medical hypothesis on pathophysiology of psychogenic polydipsia in psychiatric patients.BackgroundCompulsive behaviours, which aim to reduce distress, are common in severe psychosis, autistic spectrum disorders and...

Introduction: Diet and dietary interventions have drawn considerable attention in the literature as etiopathogenic factors and therapeutic approaches to Autism Spectrum Disorders (ASD), respectively. The objective of this study was to determine the influence of a gluten-free, casein-free (GFCF) diet on the alterations of behavior in children and adolescents diagnosed with ASD. We also aim to explore the possible association between ASD symptoms and urinary concentrations of beta-casomorphin. Methods: A total of 28 patients were recruited for this crossover clinical trial. Patients followed a normal diet (including gluten and casein) for three months and a GFCF diet for another three months. The order of the intervention —i.e., beginning with normal diet or with GFCF diet— was determined at random. The subjects were evaluated at three time points: at the onset of the study, after the first diet, and after the second diet. Each evaluation entailed three questionnaires on behavior and autism, a food frequency questionnaire (to determine adherence to the diet) and a determination of concentrations of beta-casomorphin in urine using chromatographic techniques. Results: No significant behavioral changes were found after a GFCF diet. No association was found between ASD symptoms and urinary concentrations of beta-casomorphin. Conclusion: A GFCF diet followed for three months do neither show significant changes in behavioral symptoms of autism nor in urine concentrations of beta-casomorphin using chromatographic detection. However, we need further studies including elements of placebo and double-blindness and more sophisticated beta-casomorphin detection techniques to better define subjects who might benefit from these diets.

Diet therapy for autism spectrum disorders (ASD) remains one of the most popular alternative therapies. despite conflicting opinions regarding the effectiveness of the dietary approach. According to the theory of exorphin intoxication, gluten and casein peptides enter the bloodstream through the mucous membrane of the small intestine, penetrate the blood-brain barrier and affect the neurons of the cerebral cortex. The wellknown hypothesis of the relationship between autism and gluten intolerance is based on this theory. The aim of this work was to study the correlation between the blood concentration of intestinal fatty acid - binding protein (I-FABP) and gliadomorphin and casomorphin as markers of opioid intoxication, depending on the use of diet therapy in children with ASD. Material and methods. The study included 85 patients aged 3 to 15 years with an established diagnosis of ASD. The first group consisted of 36 children who followed a gluten-free diet (GFD) for at least 6 months, 3 of them also followed a casein-free diet (CFD), the second group included 49 patients with ASD who had no dietary restrictions. The concentration of I-FABP, gliadomorphin, and casomorphin in the blood serum was determined by enzyme immunoassay in all patients. Results. In children with ASD who followed GDD, the average values of the studied parameters were significantly lower than in patients with ASD who have no dietary restrictions: gliadomorphine - 0.98±1.27 vs 1.68±0.97 ng/ml, casomorphine - 1.62± 0.76 vs 2.37±0.53 pg/ml, I-FABP - 156.2±102.16 vs 528.26±255.95 pg/ml (p0.01). In patients with ASD using diet therapy, there was a significant increase in gliadomorifin (r=0.64, p=0.0001) and casomorphin (r=0.53, p=0.001) with an increase in I-FABP. In children with ASD, not adhering GFD, there was also an increase in blood gliadomorphin (r=0.30, p=0.036) with an increase in I-FABP level; this trend was not observed relative to casomorphin (r=-0.0050, p=0.973). Perhaps, with the expansion of the sample, this pattern will also be observed in children who are on a regular diet. Conclusion. When including diet therapy in the therapeutic treatment of autism, it is necessary to take into account the individual intolerance to gluten and casein, conduct additional examinations in order to specify the nature of the intolerance and the need to prescribe a diet.

Oxymatrine and Gut Microbiota Modulation: A Potential Therapeutic Strategy for Bone Cancer Pain Management

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication and interaction problems. The prevalence of ASD is increasing globally, with a higher ratio of males to females. Gastrointestinal symptoms are common in individuals with ASD, and gut microbiota has been implicated in the disorder’s development. This study aimed to investigate the gut microbiota alteration in Thai individuals with ASD compared to healthy controls using 16S rRNA gene sequencing. The influence of gender and age on gut microbiota composition and function was also examined. A total of 65 ASD individuals and 30 neurotypical (NT) individuals were included in the analysis. The results revealed notable differences in gut microbiota composition between the ASD and NT groups, with variations observed in microbial richness and the presence of enriched microbial taxa. These differences were influenced by both gender and age. Fusobacteriota, Fusobacteriaceae, and Fusobacterium were found to be enriched in individuals with ASD. Furthermore, the study identified gender-related taxa, such as Bacteroides plebeius, enriched in ASD females. Age-related taxa, including Veillonella, known to be associated with poor oral hygiene, were also observed in ASD children. The analysis of differentially abundant pathways highlighted the enrichment of various metabolic pathways in individuals with ASD, including those related to endocrine-disrupting chemicals. These findings underscore the importance of considering gender and age when studying gut microbiota in ASD. They provide valuable insights into the potential role of gut microbiota dysbiosis in ASD pathogenesis and highlight the influence of environmental factors.

Cardiovascular changes under the microgravity environment and the gut microbiome

Autism spectrum disorder (ASD) is a severe, complex neurodevelopmental disorder, characterized by impairments in social interaction and communication with restricted and stereotyped behavior patterns. ASD symptoms result from a complex interaction between genetic and environment factors. Food intolerances, allergies, altered intestinal permeability (leaky gut), immune dysregulation, neuroinflammation and oxidative stress may trigger ASD symptoms. ASD patients have shown increased urinary levels of β-casomorphin and gliadorphin peptides produced by incomplete digestion of gluten proteins and milk casein. “Leaky gut” may facilitate the transport of these peptides into the central nervous system (CNS) inducing direct “opioid activity” and thus affecting neurotransmission. ASD patients on gluten and/or casein-free diet have shown improvement in most behavior and cognitive scores. Immune dysregulation leads to a neuroinflammatory response that correlates between immune dysfunction with behavioral and cognitive impairments in ASD patients. Genetic variants of the MET gene (7q31.2) are risk factors for ASD. The MET receptor participates in brain cortex and cerebellum development and in gastrointestinal and immunological functions. A high percentage of ASD children have shown non-celiac gluten sensitivity, an immune reaction against gluten in subjects not affected with celiac disease with prominent mucosal eosinophil infiltration and increased blood eosinophilia. ASD patients have shown alterations in brain anatomy involved in language and social interaction skills, correlating with specific aspects of ASD symptoms. ASD behavior results from abnormal interactions between the opioid system and various pathways together with anatomical alterations in the CNS. Individualized diagnosis and prognostic predictions should provide effective personalized therapies in ASD patients.

Objectives Inappropriate vitamin supply is a public health problem and is related to abnormalities in brain development, immune response and, more recently, in changes of gut microbial composition. It is known that low levels of vitamin in early life are linked to increased susceptibility to neurodevelopmental disorders, such as Autism Spectrum Disorders (ASD). Unfortunately, the possible peripheral influences of vitamin deficiency that leads to alterations in the gut microbiota-immune-brain axis, one important modulator of the ASD pathology, remain unclear. This narrative review discusses how the impact of vitamin deficiency results in changes in the immune regulation and in the gut microbiota composition, trying to understand how these changes may contribute for the development and severity of ASD. Methods The papers were selected using Pubmed and other databases. This review discusses the following topics: (1) vitamin deficiency in alterations of central nervous system in autism, (2) the impact of low levels of vitamins in immunomodulation and how it can favor imbalance in gut microbiota composition and gastrointestinal (GI) disturbances, (3) gut microbiota imbalance/inflammation associated with the ASD pathophysiology, and (4) possible evidences of the role of vitamin deficiency in dysfunctional gut microbiota-immune-brain axis in ASD. Results Studies indicate that hypovitaminosis A, B12, D, and K have been co-related with the ASD neuropathology. Furthermore, it was shown that low levels of these vitamins favor the Th1/Th17 environment in the gut, as well as the growth of enteropathogens linked to GI disorders. Discussion GI disorders and alterations in the gut microbiota-immune-brain axis seems to be linked with ASD severity. Although unclear, hypovitaminosis appears to regulate peripherally the ASD pathophysiology by modulating the gut microbiota-immune-brain axis, however, more research is still necessary to confirm this hypothesis.

Pharmacological, non-pharmacological and stem cell therapies for the management of autism spectrum disorders: A focus on human studies

Emerging evidence suggests novel cardiometabolic roles for bacterially-synthesized vitamin K forms known as menaquinones (MK-n). Though gut bacteria synthesize MK-n, relationships between gut microbiota composition, MK-n biosynthesis, and cardiometabolic health have not been examined. To examine these relationships, MK-n and microbiota composition were measured in fecal samples collected from 77 Chinese adults (41 ± 7 y, BMI 32 ± 2 kg/m2) during a 23-wk diet intervention previously shown to alter gut microbiota composition and improve cardiometabolic health. Variability in fecal MK-n content was associated with gut microbiota composition, and longitudinal changes in the relative abundance of > 100 phylotypes were associated with altered fecal content of 蠅 1 individual MK-n. The strongest and most consistent relationships were between Prevotella spp. and MK-5, -11 -12, and -13, between Bacteroides spp. and MK-9 and -10, and between Eschericia/Shigella spp. and MK-8. Baseline fecal MK-9 content was inversely associated with BMI (r = -.30, P = 0.05) and HOMA-IR (r = -.37, P = 0.01). No other cross-sectional or longitudinal associations between fecal MK-n and cardiometabolic health biomarkers were observed. Findings suggest that variability in fecal MKn content is associated with the gut microbiota, and that diet-mediated changes in gut microbiota composition may alter gut MK-n content. The implications for human health merit further investigation. Funding: Dr. James Sadowski Memorial Internship, USDA contract #58-1950-7-707, National Nature Science Foundation of China.

Symptoms characteristic of autism spectrum disorder were initially believed to protect individuals with autism spectrum disorder from developing substance abuse. However, recent studies suggest that up to 36% of individuals with autism spectrum disorder may have a co-occurring issue with substance abuse. In addition, substance abuse may worsen the difficulties with daily functioning some individuals with autism spectrum disorder experience. It is important to understand occurrence rates, and risk, protective and positive treatment factors of co-occurring autism spectrum disorder and substance abuse in order to promote the best possible support for this special population. This review aimed to find and synthesize evidence regarding risk, protective and treatment factors, and determine a general prevalence rate of co-occurring autism spectrum disorder and substance abuse from all studies on substance use and abuse in individuals with autism spectrum disorder. The review also aimed to assess study quality and identify a diagnostic measure for substance abuse in individuals with autism spectrum disorder. Twenty-six studies on substance use and abuse in autism spectrum disorder were included in the review. The rates of substance abuse among those with autism spectrum disorder identified by included studies ranged from 1.3% to 36%, but due to large differences in study methods, a general prevalence rate could not be determined. Risk and protective factors, recognized in the general population, such as familial substance abuse and co-occurring mental health issues, and factors which may be more likely to occur in individuals with autism spectrum disorder, such as limited social resources and low sensation-seeking, were identified. No diagnostic measures specific to individuals with autism spectrum disorder and substance abuse were identified. This review identified only one exploratory study on an adapted intervention for co-occurring autism spectrum disorder and substance abuse. However, there were many methodological challenges in this study that limit the conclusions that can be drawn from the data. More research, using consistent methods, is needed to understand risk and protective factors and to determine the prevalence of substance abuse among individuals with autism spectrum disorder. The potential for co-occurring autism spectrum disorder and substance abuse should be considered by professional working in both autism spectrum disorder and substance abuse services, as finding suggests substance abuse is possible among individuals with autism spectrum disorder and may occur more frequently than previously believed. In addition, autism spectrum disorder and substance abuse service providers should be sensitive to specific risk and protective factors identified by the review that may impact substance abuse course and outcomes.

Gluten- and casein-containing foods could aggravate the symptoms of children and adolescents with autism spectrum disorder (ASD), and subsequently impact their quality of life. However, there is a mixed opinion among researchers concerning the impact of alternative diet on reducing ASD symptoms. This scoping review aimed at examining the impact of the "gluten-free, casein-free" (GFCF) diet on health outcomes and the quality of life among autistic children and adolescents. A scoping review of the literature was performed following the Joanna Briggs Institute (JBI) guidelines. Four databases, including EbscoHost, Medline, CINAHL, and ProQuest, were used to obtain subject-specific studies relevant to the research question and published between July 2013 and March 2024. A comprehensive search using keywords such as "autism spectrum disorder", "gluten-free diet", and "casein-free diet" was conducted to obtain articles related to the research focus area. Only full-text, peer-reviewed, written in English articles were selected. Data extraction and data analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-extension to Scoping Review (PRISMA-ScR) protocol. From the initial 586 studies, a total of 27 articles were included in the final analysis of the review. The thematic analysis included "GFCF diet and improvement of the core autistic symptoms", "the gut-brain link", "dietary interventions and autism", "possible side effects due to the GCFC diet", and "inconclusive studies and mixed opinions". A majority of the studies showed a positive effect of the GFCF diet on a variety of autistic symptoms, including positive changes in cognitive skills, behaviour, and gastrointestinal symptoms, while some showed conflicting evidence. The currently available evidence on the impact of the "GFCF" diet on the quality of life of autistic children and adolescents may warrant potentially effective interventions for alleviating symptoms of autism spectrum disorders. However, this scoping review highlights the need for more research to provide more reliable evidence on the health outcomes and quality of life of ASD sufferers to guide practice.