Altered Gut Microbiota and Short-chain Fatty Acids in Chinese Children with Constipated Autism Spectrum Disorder

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Needs review
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
He J, Gong X, Hu B, Lin L, Lin X, Gong W, Zhang B, Cao M, Xu Y, Xia R, Zheng G, Wu S, Zhang Y
Journal
Scientific reports
Year
2023
Gastrointestinal symptoms are more prevalent in children with autism spectrum disorder (ASD) than in typically developing (TD) children. Constipation is a significant gastrointestinal comorbidity of ASD, but the associations among constipated autism spectrum disorder (C-ASD), microbiota and short-chain fatty acids (SCFAs) are still debated. We enrolled 80 children, divided into the C-ASD group (n = 40) and the TD group (n = 40). In this study, an integrated 16S rRNA gene sequencing and gas chromatography-mass spectrometry-based metabolomics approach was applied to explore the association of the gut microbiota and SCFAs in C-ASD children in China. The community diversity estimated by the Observe, Chao1, and ACE indices was significantly lower in the C-ASD group than in the TD group. We observed that Ruminococcaceae_UCG_002, Erysipelotrichaceae_UCG_003, Phascolarctobacterium, Megamonas, Ruminiclostridium_5, Parabacteroides, Prevotella_2, Fusobacterium, and Prevotella_9 were enriched in the C-ASD group, and Anaerostipes, Lactobacillus, Ruminococcus_gnavus_group, Lachnospiraceae_NK4A136_group, Ralstonia, Eubacterium_eligens_group, and Ruminococcus_1 were enriched in the TD group. The propionate levels, which were higher in the C-ASD group, were negatively correlated with the abundance of Lactobacillus taxa, but were positively correlated with the severity of ASD symptoms. The random forest model, based on the 16 representative discriminant genera, achieved a high accuracy (AUC = 0.924). In conclusion, we found that C-ASD is related to altered gut microbiota and SCFAs, especially decreased abundance of Lactobacillus and excessive propionate in faeces, which provide new clues to understand C-ASD and biomarkers for the diagnosis and potential strategies for treatment of the disorder. This study was registered in the Chinese Clinical Trial Registry ( www.chictr.org.cn ; trial registration number ChiCTR2100052106; date of registration: October 17, 2021).

Experiment 1


Needs review

Curated date: 2023/11/07

Curator: Deacme

Revision editor(s): Deacme

Subjects

Location of subjects
China
Host species Species from which microbiome was sampled. Contact us to have more species added.
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 spectrum disorder atypical autism,autism spectrum disease,autism spectrum disorder,Autism Spectrum Disorders,autistic spectrum disorder,CHILD DEVELOPMENT DIS PERVASIVE,Child Development Disorders, Pervasive,Development Disorder, Pervasive,Development Disorders, Pervasive,Disorder, Autism Spectrum,Disorder, Pervasive Development,Disorders, Autism Spectrum,Disorders, Pervasive Development,PDD,PERVASIVE CHILD DEVELOPMENT DIS,Pervasive Child Development Disorders,Pervasive Development Disorder,Pervasive Development Disorders,pervasive developmental disorder - not otherwise specified,pervasive developmental disorders,Spectrum Disorder, Autism,Spectrum Disorders, Autism
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Typically developing (TD) group
Group 1 name Corresponds to the case (exposed) group for case-control studies
Constipated autism spectrum disorder (C-ASD) group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Children with autism spectrum disorder (ASD) while also experiencing constipation as an important gastrointestinal (GI) comorbidity.
Group 0 sample size Number of subjects in the control (unexposed) group
40
Group 1 sample size Number of subjects in the case (exposed) group
40
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
3 months

Lab analysis

Sequencing type
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

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
LEfSe
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)?
No
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
3
Matched on Factors on which subjects have been matched on in a case-control study
age, sex, body mass index

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
decreased
Simpson Estimator of species richness and species evenness: more weight on species evenness
unchanged
Richness Number of species
decreased

Signature 1

Needs review

Curated date: 2023/11/07

Curator: Deacme

Revision editor(s): Deacme

Source: Figure 3

Description: Discriminative taxa between the typically developing (TD) group and constipated autism spectrum disorder (C-ASD) group.

Abundance in Group 1: increased abundance in Constipated autism spectrum disorder (C-ASD) group

NCBI Quality ControlLinks
Barnesiella
Candidatus Stoquefichus
Comamonas
Coprobacter
Coprococcus
Desulfovibrio
Enorma
Fusobacterium
Megamonas
Odoribacter
Parabacteroides
Paraprevotella
Peptoclostridium
Peptococcus
Phascolarctobacterium
Ruminiclostridium
Victivallis

Revision editor(s): Deacme

Signature 2

Needs review

Curated date: 2023/11/07

Curator: Deacme

Revision editor(s): Deacme

Source: Figure 3

Description: Discriminative taxa between the typically developing (TD) group and constipated autism spectrum disorder (C-ASD) group.

Abundance in Group 1: decreased abundance in Constipated autism spectrum disorder (C-ASD) group

NCBI Quality ControlLinks
Aerococcus
Anaerostipes
Coriobacteriaceae
Corynebacterium
Eubacterium xylanophilum
Lachnoclostridium
Lachnospira eligens
Lactobacillus
Listeria
Longilinea
Marvinbryantia
Methylobacterium
Microbacterium
Pseudomonas
Ralstonia
Sphaerochaeta
Staphylococcus
Thomasclavelia
Treponema
Tyzzerella
[Eubacterium] brachy
[Ruminococcus] gnavus
Lachnospiraceae bacterium NK4A136
Lachnospiraceae
Prevotellaceae

Revision editor(s): Deacme