Clinical Trial Details
— Status: Recruiting
Administrative data
NCT number |
NCT05830591 |
Other study ID # |
RC 20/21 |
Secondary ID |
|
Status |
Recruiting |
Phase |
|
First received |
|
Last updated |
|
Start date |
May 20, 2021 |
Est. completion date |
December 31, 2023 |
Study information
Verified date |
April 2023 |
Source |
IRCCS Burlo Garofolo |
Contact |
Manola Comar, BSc |
Phone |
+39.040.3785.527 |
Email |
manola.comar[@]burlo.trieste.it |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational
|
Clinical Trial Summary
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
Description:
Autism Spectrum Disorder (ASD) is a neurodevelopment disorder characterized by impairment in
social interaction, communication, and behavior, as well as sensory challenges. In addition
to the main symptoms, secondary symptoms can appear, such as gastrointestinal disorders. Gut
microbiota has an important role in the harvest of nutrients and energy from our diet.
Furthermore, 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. For
instance, 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 (like some short-chain fatty acids: acetate and propionate) or an increment of
Sutterella spp. and Ruminococcus torques in feces of ASD children, which are negatively
associated with the health of the gut. Similarly, very 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: as a matter of fact, 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. Interestingly, 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 gastro-intestinal (GI) tract,
given the transit of bacteria from the oral cavity to the gut, leading to different effects
depending on the type of bacteria. This implies that an oral microbiota dysbiosis may be one
of the leading causes of the gut microbiota dysbiosis reported in numerous ASD studies as
demonstrated by studies of the Human Microbiome Project, the 45% of the gut and oral
microbiota bacteria over-lap. In light of these facts, the oral microbiota could have a
significant role within the ASD-associated GI disorders and CNS inflammation. The main
objective of this project is to identify descriptive features relative to bacterial species
in gut and oral microbiota of pediatric subjects with ASD diagnosis. The purpose is to find
whether these species overlap in order to identify descriptive features of ASD, which are
collectable by means of a simple oral swab (rather than a fecal sample). These species will
be identified with both DNA sequencing, followed by bioinformatic analysis, and a culturomic
approach. The innovative approach of "network analysis" will be employed in order to find
definite bacterial consortia, named Species Interacting Groups (SIGs) able to collect the
abovementioned featuring species. These data could be useful for a better ASD description in
terms of bacterial compositional differences, especially within a defined pediatric group.