Gut-oral Axis Microbiome in Autism Spectrum Disorders

Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age1-17
SponsorIRCCS Burlo Garofolo

About this trial

Autism Spectrum Disorder (ASD) is a neurodevelopment disorder characterized by impairment in social interaction, communication, and behavior, as well as sensory challenges. In addition, secondary symptoms can appear, such as gastrointestinal disorders. Gut microbiota has an important role in the harvest of nutrients and energy from our diet. It influences a wide range of metabolic, developmental, and physiological processes such as the maintenance of the gut epithelial layer, immune system development, protection against pathogens, detoxification and xenobiotics degradation. The ecosystem of a healthy human gastrointestinal (GI) tract is mainly populated by Firmicutes and Bacteroidetes phyla, to a lesser extent by Actinobacteria and Proteobacteria, in this case the microbiota is in an eubiosis condition. Whether a disturbance of the microbial ecosystem occurs, gut microbiota is in a dysbiosis condition and it could lead different metabolic disorders. The two-way communication between gut microbiota and central nervous system (CNS) affects stress response, pain perception, neurochemistry and several disorders. The gut microbiota in ASD patients revealed some peculiarities such as the high percentage of Propionibacter and Clostridium, well known for their production of pro inflammatory metabolites, or an increment of Sutterella spp. and Ruminococcus torques, which are negatively associated with the health of the gut. Recent studies suggest that also the oral microbiota may be involved in ASD symptoms assuming the existence of a "microbiota-oral-brain axis". ASD patients are often suffering of several oral cavity disorders like caries, gingivitis and periodontitis, probably due to the poor oral hygiene. These disorders are linked to a dysbiosis of the oral microbiota: the characterization of the ASD subjects oral microbiota showed a lower biodiversity of bacteria species and different levels of specific bacteria, comparing to the controls. Several studies suggest that some bacteria species invade the blood-brain barriers as well as their metabolites, triggering inflammatory response and an alteration of the metabolic activity in the CNS. It has been demonstrated that ASD patients have a high level of pro-inflammatory cytokines and chemokines in the cerebrospinal fluid and an upregulation of the microglia. The oral microbiota could also affect the lower GI tract and have a significant role within the ASD-associated GI disorders and CNS inflammation

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Caucasian

Diagnosed with ASD or with a newly formulated diagnosis of ASD

Aged between 1 and 17 years

Caucasian

Disqualifiers

Antibiotic use in the month before sample collection

Probiotic use in the month before sample collection

Other neurological diseases

Chronic inflammatory diseases

Trial population

Pediatric subjects: * children coming to the Division of Child Neurology and Psychiatry for the first clinical evaluation (1 year to 5 years old) * children with confirmed ASD diagnosis (6 years to 17 years old) coming to the Odonto-Stomatology Department for the periodical dental hygiene session. * children control group with matched demographic characteristics accessing our Institute for different purposes

Trial design

Design model

Other

Time perspective

Cross-sectional

Treatments tested in this trial

  • Characterization of the microbiome in oral and fecal samples

    Other intervention

    The oral and fecal samples are collected during the periodical dental hygiene session at the odonto-stomatology unit and during day hospital for younger children admitted for the first clinical evaluation at Division of Child Neurology and Psychiatry. Procedures will follow standardized protocols.

Treatment groups

86 Participants
are divided into 3 treatment groups
Group A: Children with autism disorders 1-5 years1 intervention
Group B: Children with autism disorders 6-17 years1 intervention
Group C: Children control group1 intervention

Trial outcomes

Primary outcomes

1

To compare oral and GI microbiota

Oral and GI bacterial species will be evaluated in oral and fecal samples collected and compared through bioinformatic and statistical analysis among case and control groups to isolate the discriminant ones. The technical activity is focused on samples DNA extraction and sequencing and on a culturomic approach.

Time frame
At baseline

Secondary outcomes

1

To evaluate the association between the key bacteria species found in ASD microbiota and soluble concentration of salivary cytokines

Oral and GI bacterial species will be evaluated in oral and fecal samples. The soluble concentrations (picograms per millilitre) of a panel of 27 cytokines and chemokines will be simultaneously assessed in saliva samples.

Time frame
At baseline
2

To evaluate the association between the key bacteria species found in ASD microbiota and soluble concentration of salivary chemokines

Oral and GI bacterial species will be evaluated in oral and fecal samples. The soluble concentrations (picograms per millilitre) of a panel of 27 cytokines and chemokines will be simultaneously assessed in saliva samples.

Time frame
At baseline
3

To evaluate the association between the microbiota structure and the severity of the ASD symptoms

Oral and GI bacterial species will be evaluated in oral and fecal samples. Clinical data will be collected from medical records.

Time frame
At baseline
4

To evaluate the association between the microbiota structure and eating habits of ASD children

A food diary will be distributed at enrollment to evaluate eating habits of ASD children

Time frame
At baseline

Other outcomes

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