Autism Spectrum Disorder (ASD) with and without Mental Regression is Associated with Changes in the Fecal Microbiota

From BugSigDB
Reviewed Marked as Reviewed by Claregrieve1 on 15 July 2022
study design
case-control
Citation
PMID
URI
Authors
Plaza-Díaz J, Gómez-Fernández A, Chueca N, Torre-Aguilar MJ, Gil Á, Perez-Navero JL, Flores-Rojas K, Martín-Borreguero P, Solis-Urra P, Ruiz-Ojeda FJ, Garcia F, Gil-Campos M
Journal
Nutrients
Year
2019
New microbiome sequencing technologies provide novel information about the potential interactions among intestinal microorganisms and the host in some neuropathologies as autism spectrum disorders (ASD). The microbiota⁻gut⁻brain axis is an emerging aspect in the generation of autistic behaviors; evidence from animal models suggests that intestinal microbial shifts may produce changes fitting the clinical picture of autism. The aim of the present study was to evaluate the fecal metagenomic profiles in children with ASD and compare them with healthy participants. This comparison allows us to ascertain how mental regression (an important variable in ASD) could influence the intestinal microbiota profile. For this reason, a subclassification in children with ASD by mental regression (AMR) and no mental regression (ANMR) phenotype was performed. The present report was a descriptive observational study. Forty-eight children aged 2⁻6 years with ASD were included: 30 with ANMR and 18 with AMR. In addition, a control group of 57 normally developing children was selected and matched to the ASD group by sex and age. Fecal samples were analyzed with a metagenomic approach using a next-generation sequencing platform. Several differences between children with ASD, compared with the healthy group, were detected. Namely, Actinobacteria and Proteobacteria at phylum level, as well as, Actinobacteria, Bacilli, Erysipelotrichi, and Gammaproteobacteria at class level were found at higher proportions in children with ASD. Additionally, Proteobacteria levels showed to be augmented exclusively in AMR children. Preliminary results, using a principal component analysis, showed differential patterns in children with ASD, ANMR and AMR, compared to healthy group, both for intestinal microbiota and food patterns. In this study, we report, higher levels of Actinobacteria, Proteobacteria and Bacilli, aside from Erysipelotrichi, and Gammaproteobacteria in children with ASD compared to healthy group. Furthermore, AMR children exhibited higher levels of Proteobacteria. Further analysis using these preliminary results and mixing metagenomic and other "omic" technologies are needed in larger cohorts of children with ASD to confirm these intestinal microbiota changes.

Experiment 1


Reviewed Marked as Reviewed by Claregrieve1 on 15 July 2022

Curated date: 2021/01/10

Curator: WikiWorks743

Revision editor(s): WikiWorks753, WikiWorks743, Claregrieve1, WikiWorks

Subjects

Location of subjects Country from which study subjects were recruited
Spain
Host species Species from which microbiome was sampled (if applicable)
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
autism autism,autism (disease),autism spectrum disorder,Autism, Early Infantile,Autism, Infantile,autism, susceptiblity to,Autisms,Autistic Disorder,autistic disorder,autistic disorder of childhood onset,Autistic disorder of childhood onset (disorder),childhood autism,Disorder, Autistic,Disorders, Autistic,Early Infantile Autism,Infantile Autism,infantile autism,Infantile autism (disorder),Infantile Autism, Early,Infantile psychosis (disorder),Kanner Syndrome,Kanner's Syndrome,Kanner's syndrome,Kanners Syndrome,Syndrome, Kanner's
Group 0 name Corresponds to the control (unexposed) group for case-control studies
children with autism non-mental regression (ANMR)
Group 1 name Corresponds to the case (exposed) group for case-control studies
children with autism mental regression (AMR)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Children between 2-6 years old with an agreed clinical diagnosis of autism per the ICD 10th Edition for ASD and DSM-5 who had development regression during the first two years of life.
Group 0 sample size Number of subjects in the control (unexposed) group
30
Group 1 sample size Number of subjects in the case (exposed) group
18

Lab analysis

Sequencing type Experimental technique used for quantifying microbial abundance
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V4
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Statistical test Statistical test or computational tool used for differential abundance testing
Kruskall-Wallis
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes



Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 15 July 2022

Curated date: 2020-01-28

Curator: Shaimaa Elsafoury

Revision editor(s): WikiWorks743

Source: Table 2 & Table 3

Description: Relative abundances of bacteria in fecal microbiota of children with ASD (AMR or ANMR) and healthy children.

Abundance in Group 1: increased abundance in children with autism mental regression (AMR)

NCBI Links
Proteobacteria
Enterococcus

Revision editor(s): WikiWorks743

Experiment 2


Reviewed Marked as Reviewed by Claregrieve1 on 15 July 2022

Curated date: 2021/01/10

Curator: WikiWorks743

Revision editor(s): WikiWorks753, WikiWorks743, Claregrieve1

Subjects

Location of subjects Country from which study subjects were recruited
Spain
Host species Species from which microbiome was sampled (if applicable)
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
autism autism,autism (disease),autism spectrum disorder,Autism, Early Infantile,Autism, Infantile,autism, susceptiblity to,Autisms,Autistic Disorder,autistic disorder,autistic disorder of childhood onset,Autistic disorder of childhood onset (disorder),childhood autism,Disorder, Autistic,Disorders, Autistic,Early Infantile Autism,Infantile Autism,infantile autism,Infantile autism (disorder),Infantile Autism, Early,Infantile psychosis (disorder),Kanner Syndrome,Kanner's Syndrome,Kanner's syndrome,Kanners Syndrome,Syndrome, Kanner's
Group 0 name Corresponds to the control (unexposed) group for case-control studies
healthy controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
children with autism non-mental regression (ANMR)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Children between 2-6 years old with an agreed clinical diagnosis of autism per the ICD 10th Edition for ASD and DSM-5 who did not have development regression during the first two years of life.
Group 0 sample size Number of subjects in the control (unexposed) group
57
Group 1 sample size Number of subjects in the case (exposed) group
30

Lab analysis

Sequencing type Experimental technique used for quantifying microbial abundance
16S
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Statistical test Statistical test or computational tool used for differential abundance testing
Kruskall-Wallis
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes
Matched on Factors on which subjects have been matched on in a case-control study
age, sex


Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 15 July 2022

Curated date: 2020-01-28

Curator: Shaimaa Elsafoury

Revision editor(s): WikiWorks743, Claregrieve1

Source: Table 2, Figure 2 & Table 3

Description: Relative abundances of bacteria in fecal microbiota of children with ANMR ASD and healthy children.

Abundance in Group 1: increased abundance in children with autism non-mental regression (ANMR)

NCBI Links
Actinobacteria
Actinomycetia
Bifidobacteriaceae
Bifidobacterium
Enterocloster bolteae
Microbacteriaceae
Thermoanaerobacteraceae
Enterococcus

Revision editor(s): WikiWorks743, Claregrieve1

Experiment 3


Reviewed Marked as Reviewed by Claregrieve1 on 15 July 2022

Curated date: 2021/01/10

Curator: WikiWorks743

Revision editor(s): WikiWorks753, WikiWorks743, Claregrieve1

Subjects

Location of subjects Country from which study subjects were recruited
Spain
Host species Species from which microbiome was sampled (if applicable)
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
autism autism,autism (disease),autism spectrum disorder,Autism, Early Infantile,Autism, Infantile,autism, susceptiblity to,Autisms,Autistic Disorder,autistic disorder,autistic disorder of childhood onset,Autistic disorder of childhood onset (disorder),childhood autism,Disorder, Autistic,Disorders, Autistic,Early Infantile Autism,Infantile Autism,infantile autism,Infantile autism (disorder),Infantile Autism, Early,Infantile psychosis (disorder),Kanner Syndrome,Kanner's Syndrome,Kanner's syndrome,Kanners Syndrome,Syndrome, Kanner's
Group 0 name Corresponds to the control (unexposed) group for case-control studies
healthy controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
children with autism mental regression (AMR)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Children between 2-6 years old with an agreed clinical diagnosis of autism per the ICD 10th Edition for ASD and DSM-5 who had development regression during the first two years of life.
Group 0 sample size Number of subjects in the control (unexposed) group
57
Group 1 sample size Number of subjects in the case (exposed) group
18

Lab analysis

Sequencing type Experimental technique used for quantifying microbial abundance
16S
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Statistical test Statistical test or computational tool used for differential abundance testing
Kruskall-Wallis
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes
Matched on Factors on which subjects have been matched on in a case-control study
age, sex


Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 15 July 2022

Curated date: 2020-01-28

Curator: Shaimaa Elsafoury

Revision editor(s): WikiWorks743, Claregrieve1

Source: Table 2, Figure 2 & Table 3

Description: Relative abundances of bacteria in fecal microbiota of children with AMR ASD and healthy children.

Abundance in Group 1: increased abundance in children with autism mental regression (AMR)

NCBI Links
Bifidobacteriaceae
Bifidobacterium
Enterocloster bolteae
Enterococcus
Microbacteriaceae
Proteobacteria
Thermoanaerobacteraceae

Revision editor(s): WikiWorks743, Claregrieve1

Experiment 4


Reviewed Marked as Reviewed by Claregrieve1 on 15 July 2022

Curated date: 2021/01/10

Curator: WikiWorks743

Revision editor(s): WikiWorks753, WikiWorks743, Claregrieve1

Subjects

Location of subjects Country from which study subjects were recruited
Spain
Host species Species from which microbiome was sampled (if applicable)
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
autism autism,autism (disease),autism spectrum disorder,Autism, Early Infantile,Autism, Infantile,autism, susceptiblity to,Autisms,Autistic Disorder,autistic disorder,autistic disorder of childhood onset,Autistic disorder of childhood onset (disorder),childhood autism,Disorder, Autistic,Disorders, Autistic,Early Infantile Autism,Infantile Autism,infantile autism,Infantile autism (disorder),Infantile Autism, Early,Infantile psychosis (disorder),Kanner Syndrome,Kanner's Syndrome,Kanner's syndrome,Kanners Syndrome,Syndrome, Kanner's
Group 0 name Corresponds to the control (unexposed) group for case-control studies
healthy controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
children with autism spectrum disorders (ASD)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Children between 2-6 years old with an agreed clinical diagnosis of autism per the ICD 10th Edition for ASD and DSM-5
Group 0 sample size Number of subjects in the control (unexposed) group
57
Group 1 sample size Number of subjects in the case (exposed) group
48

Lab analysis

Sequencing type Experimental technique used for quantifying microbial abundance
16S
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Statistical test Statistical test or computational tool used for differential abundance testing
Kruskall-Wallis
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes
Matched on Factors on which subjects have been matched on in a case-control study
age, sex


Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 15 July 2022

Curated date: 2020-01-28

Curator: Shaimaa Elsafoury

Revision editor(s): WikiWorks743, Claregrieve1

Source: Figure 1

Description: Relative abundances of bacteria in fecal microbiota of children with ASD (AMR or ANMR) and healthy children.

Abundance in Group 1: increased abundance in children with autism spectrum disorders (ASD)

NCBI Links
Bacillaceae
Bifidobacteriaceae
Corynebacteriaceae
Desulfohalobiaceae
Enterobacteriaceae
Enterococcaceae
Erysipelotrichaceae
Microbacteriaceae
Thermoactinomycetaceae
Fusobacteriaceae

Revision editor(s): WikiWorks743, Claregrieve1

Signature 2

Reviewed Marked as Reviewed by Claregrieve1 on 15 July 2022

Curated date: 2020-01-28

Curator: Shaimaa Elsafoury

Revision editor(s): WikiWorks743

Source: Figure 1

Description: Relative abundances of bacteria in fecal microbiota of children with ASD (AMR or ANMR) and healthy children.

Abundance in Group 1: decreased abundance in children with autism spectrum disorders (ASD)

NCBI Links
Lachnospiraceae

Revision editor(s): WikiWorks743