Children with autistic spectrum disorders (ASDs) tend to suffer from severe gastrointestinal problems. Such symptoms may be due to a disruption of the indigenous gut flora promoting the overgrowth of potentially pathogenic micro-organisms. The faecal flora of patients with ASDs was studied and compared with those of two control groups (healthy siblings and unrelated healthy children). Faecal bacterial populations were assessed through the use of a culture-independent technique, fluorescence in situ hybridization, using oligonucleotide probes targeting predominant components of the gut flora. The faecal flora of ASD patients contained a higher incidence of the Clostridium histolyticum group (Clostridium clusters I and II) of bacteria than that of healthy children. However, the non-autistic sibling group had an intermediate level of the C. histolyticum group, which was not significantly different from either of the other subject groups. Members of the C. histolyticum group are recognized toxin-producers and may contribute towards gut dysfunction, with their metabolic products also exerting systemic effects. Strategies to reduce clostridial population levels harboured by ASD patients or to improve their gut microflora profile through dietary modulation may help to alleviate gut disorders common in such patients.

https://www.ncims.com/wp-content/uploads/2016/01/Autism-and-Digestive-Bacteria.pdf

Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children

Autism spectrum disorders (ASD) are part of a broad spectrum of neurodevelopmental disorders known as pervasive developmental disor- ders, which occur in childhood. They are charac- terized by impairments in social interaction, verbal and nonverbal communication and the presence of restricted and repetitive stereotyped behaviors. At the present time, the etiology of ASD is largely unknown, but genetic, environmental, immunolog- ical, and neurological factors are thought to play a role in the development of ASD. Recently, increas- ing research has focused on the connections be- tween the immune system and the nervous system, including its possible role in the development of ASD. These neuroimmune interactions begin early during embryogenesis and persist throughout an individual's lifetime, with successful neurodevelop- ment contingent upon a normal balanced immune response. Immune aberrations consistent with a dysregulated immune response, which so far, have been reported in autistic children, include abnor- mal or skewed T helper cell type 1 (TH1)/TH2 cytokine profiles, decreased lymphocyte numbers, decreased T cell mitogen response, and the imbal- ance of serum immunoglobulin levels. In addition, autism has been linked with autoimmunity and an association with immune-based genes including hu- man leukocyte antigen (HLA)-DRB1 and comple- ment C4 alleles described. There is potential that such aberrant immune activity during vulnerable and critical periods of neurodevelopment could participate in the generation of neurological dys- function characteristic of ASD. This review will examine the status of the research linking the im- mune response with ASD. J. Leukoc. Biol. 80: 1-15; 2006.

/pdf/the-immune-response-in-autism-a-new-frontier-for-autism-233xc007f8.pdf

The immune response in autism: a new frontier for autism research

Objectives: Intestinal permeability (IPT) was investigated in patients with autism as well as in their first-degree relatives to investigate leaky gut hypothesis. Faecal calprotectin (FC) was also measured in patients with autism, either with or without gastrointestinal symptoms, and in their firstdegree relatives. Patients and Methods: IPT results, assessed by means of the lactulose/ mannitol test, were compared with adult and child controls and with FC values. Results: A high percentage of abnormal IPT values were found among patients with autism (36.7%) and their relatives (21.2%) compared with normal subjects (4.8%). Patients with autism on a reported gluten-casein– free diet had significantly lower IPT values compared with those who were on an unrestricted diet and controls. Gastrointestinal symptoms were present in 46.7% of children with autism: constipation (45.5%), diarrhoea (34.1%), and others (alternating diarrhoea/constipation, abdominal pain, etc: 15.9%). FC was elevated in 24.4% of patients with autism and in 11.6% of their relatives; it was not, however, correlated with abnormal IPT values. Conclusions: The results obtained support the leaky gut hypothesis and indicate that measuring IPT could help to identify a subgroup of patients with autism who could benefit from a gluten-free diet. The IPT alterations found in first-degree relatives suggest the presence of an intestinal (tightjunction linked) hereditary factor in the families of subjects with autism.

Alterations of the intestinal barrier in patients with autism spectrum disorders and in their first-degree relatives.

Gastrointestinal disturbances are commonly reported in children with autism, complicate clinical management, and may contribute to behavioral impairment. Reports of deficiencies in disaccharidase enzymatic activity and of beneficial responses to probiotic and dietary therapies led us to survey gene expression and the mucoepithelial microbiota in intestinal biopsies from children with autism and gastrointestinal disease and children with gastrointestinal disease alone. Ileal transcripts encoding disaccharidases and hexose transporters were deficient in children with autism, indicating impairment of the primary pathway for carbohydrate digestion and transport in enterocytes. Deficient expression of these enzymes and transporters was associated with expression of the intestinal transcription factor, CDX2. Metagenomic analysis of intestinal bacteria revealed compositional dysbiosis manifest as decreases in Bacteroidetes, increases in the ratio of Firmicutes to Bacteroidetes, and increases in Betaproteobacteria. Expression levels of disaccharidases and transporters were associated with the abundance of affected bacterial phylotypes. These results indicate a relationship between human intestinal gene expression and bacterial community structure and may provide insights into the pathophysiology of gastrointestinal disturbances in children with autism.

/pdf/impaired-carbohydrate-digestion-and-transport-and-mucosal-1ro1vz9pdo.pdf

Impaired Carbohydrate Digestion and Transport and Mucosal Dysbiosis in the Intestines of Children with Autism and Gastrointestinal Disturbances

Invited review: Milk protein polymorphisms in cattle: Effect on animal breeding and human nutrition

Impaired social interaction, communication and imaginative skills characterize autistic syndromes. In these syndromes urinary peptide abnormalities, derived from gluten, gliadin, and casein, are reported. They reflect processes with opioid effect. The aim of this single blind study was to evaluate effect of gluten and casein-free diet for children with autistic syndromes and urinary peptide abnormalities. A randomly selected diet and control group with 10 children in each group participated. Observations and tests were done before and after a period of 1 year. The development for the group of children on diet was significantly better than for the controls.

A randomised, controlled study of dietary intervention in autistic syndromes.

Probable etiology and possible treatment of childhood autism.

Dietary intervention in autistic syndromes.

Autistic syndromes are characterized by impaired social, communicative, and imaginative skills. Urinary peptide abnormalities, in part due to gluten and casein, have been detected in some individua...

Effect of a Dietary Intervention on Autistic Behavior

Autism is a developmental disorder for which no cure currently exists. Gluten and/or casein free diet has been implemented to reduce autistic behaviour, in addition to special education, since early in the eighties. Over the last twelve years various studies on this dietary intervention have been published in addition to anecdotal, parental reports. The scientific studies include both groups of participants as well as single cases, and beneficial results are reported in all, but one study. While some studies are based on urinary peptide abnormalities, others are not. The reported results are, however, more or less identical; reduction of autistic behaviour, increased social and communicative skills, and reappearance of autistic traits after the diet has been broken.

Magne Nødland

Papers

A randomised, controlled study of dietary intervention in autistic syndromes.

Probable etiology and possible treatment of childhood autism.

Dietary intervention in autistic syndromes.

Effect of a Dietary Intervention on Autistic Behavior

Reports on dietary intervention in autistic disorders.