Altered gut microbial profile is associated with abnormal metabolism activity of Autism Spectrum Disorder

From BugSigDB
Needs review
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Dan Z, Mao X, Liu Q, Guo M, Zhuang Y, Liu Z, Chen K, Chen J, Xu R, Tang J, Qin L, Gu B, Liu K, Su C, Zhang F, Xia Y, Hu Z, Liu X
Journal
Gut microbes
Year
2020
Keywords:
16s rRNA, ASD, gut microbiota, metabolism, metagenomics, neurotransmitter
Autism Spectrum Disorder (ASD) is a severe neurodevelopmental disorder. To enhance the understanding of the gut microbiota structure in ASD children at different ages as well as the relationship between gut microbiota and fecal metabolites, we first used the 16S rRNA sequencing to evaluate the gut microbial population in a cohort of 143 children aged 2-13 years old. We found that the α-diversity of ASD group showed no significant change with age, while the TD group showed increased α-diversity with age, which indicates that the compositional development of the gut microbiota in ASD varies at different ages in ways that are not consistent with TD group. Recent studies have shown that chronic constipation is one of the most commonly obvious gastrointestinal (GI) symptoms along with ASD core symptoms. To further investigate the potential interaction effects between ASD and GI symptoms, the 30 C-ASD and their aged-matched TD were picked out to perform metagenomics analysis. We observed that C-ASD group displayed decreased diversity, depletion of species of Sutterella, Prevotella, and Bacteroides as well as dysregulation of associated metabolism activities, which may involve in the pathogenesis of C-ASD. Consistent with metagenomic analysis, liquid chromatography-mass spectrometry (LC/MS) revealed some of the differential metabolites between C-ASD and TD group were involved in the metabolic network of neurotransmitters including serotonin, dopamine, histidine, and GABA. Furthermore, we found these differences in metabolites were associated with altered abundance of specific bacteria. The study suggested possible future modalities for ASD intervention through targeting the specific bacteria associated with neurotransmitter metabolism.

Experiment 1


Needs review

Curated date: 2024/12/11

Curator: AlishaM

Revision editor(s): AlishaM

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,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,Autism spectrum disorder
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Typically developing individuals
Group 1 name Corresponds to the case (exposed) group for case-control studies
Children with Autism Spectrum Disorder (ASD)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition
Group 0 sample size Number of subjects in the control (unexposed) group
143
Group 1 sample size Number of subjects in the case (exposed) group
143
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
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
3.5
Matched on Factors on which subjects have been matched on in a case-control study
age, sex

Alpha Diversity

Richness Number of species
decreased

Signature 1

Needs review

Curated date: 2024/12/11

Curator: AlishaM

Revision editor(s): AlishaM

Source: Figure 1 f-g

Description: Bacterial taxa differentially abundant between TD and ASD

Abundance in Group 1: increased abundance in Children with Autism Spectrum Disorder (ASD)

NCBI Quality ControlLinks
Betaproteobacteria
Alcaligenaceae
Burkholderiales
Parasutterella
Escherichia/Shigella sp.
Enterobacterales
Enterobacteriaceae
Gammaproteobacteria
Bifidobacteriales
Bifidobacterium
Bifidobacteriaceae
Dialister
Actinomycetota
Pseudomonadota
Clostridioides

Revision editor(s): AlishaM

Signature 2

Needs review

Curated date: 2024/12/11

Curator: AlishaM

Revision editor(s): AlishaM

Source: Figure 1 f-g

Description: Bacterial taxa differentially abundant between TD and ASD

Abundance in Group 1: decreased abundance in Children with Autism Spectrum Disorder (ASD)

NCBI Quality ControlLinks
Bacteroidia
Bacteroidales
Prevotellaceae
Prevotella_9Prevotella_9
Megamonas
Ruminococcus_2Ruminococcus_2

Revision editor(s): AlishaM

Experiment 2


Needs review

Curated date: 2024/12/12

Curator: AlishaM

Revision editor(s): AlishaM

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Children with constipated Autism Spectrum Disorder (C-ASD)
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
30

Lab analysis

Statistical Analysis

Statistical test
Mann-Whitney (Wilcoxon)
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
Not specified

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Richness Number of species
increased

Signature 1

Needs review

Curated date: 2024/12/12

Curator: AlishaM

Revision editor(s): AlishaM

Source: Figure 3F, Table S6

Description: Relative abundance of species enriched in TD versus C-ASD

Abundance in Group 1: decreased abundance in Children with constipated Autism Spectrum Disorder (C-ASD)

NCBI Quality ControlLinks
Alloprevotella rava
Alloprevotella tannerae
Bacillus cereus
Bacteroidales bacterium Barb7
Bacteroides acidifaciens
Bacteroides caccae
Bacteroides clarus
Bacteroides faecichinchillae
Bacteroides fluxus
Bacteroides helcogenes
Bacteroides salyersiae
Bacteroides sp. CAG:144
Bacteroides sp. CAG:443
Bacteroides sp. CAG:462
Bacteroides sp. CAG:598
Bacteroides sp. CAG:633
Bacteroides sp. CAG:702
Bacteroides sp. CAG:875
Bacteroides sp. HMSC073E02
Bacteroides stercoris
Bacteroides stercoris CAG:120
Bacteroides timonensis
Barnesiella viscericola
Campylobacter gracilis
Clostridium botulinum
Crocosphaera watsonii
Desulfovibrio piger
Eubacterium limosum
Flavobacterium columnare
Hallella bergensis
Hoylesella nanceiensis
Hoylesella pleuritidis
Lachnospiraceae bacterium A2
Leyella stercorea CAG:629
Parabacteroides gordonii
Parabacteroides sp. CAG:409
Paraprevotella xylaniphila
Pedobacter panaciterrae
Phascolarctobacterium succinatutens
Phocaeicola barnesiae
Phocaeicola coprophilus CAG:333
Phocaeicola plebeius
Phocaeicola plebeius CAG:211
Phocaeicola salanitronis
Porphyromonas cangingivalis
Porphyromonas gingivalis
Prevotella amnii
Prevotella denticola
Prevotella fusca
Prevotella histicola
Prevotella pallens
Prevotella sp. CAG:1058
Prevotella sp. CAG:1185
Prevotella sp. CAG:279
Prevotella sp. CAG:755
Prevotella sp. CAG:891
Prevotella sp. MSX73
Prevotella sp. oral taxon 306
Pseudobutyrivibrio ruminis
Pseudomonas aeruginosa
Segatella maculosa
Segatella salivae
Selenomonas ruminantium
Streptococcus suis
Sutterella parvirubra
Xylanibacter rarus
uncultured Bacteroides sp.
Bacteroides stercorirosorisBacteroides stercorirosoris
Bacteroides ndongoniaeBacteroides ndongoniae
Bacillus sp. Soil768D1Bacillus sp. Soil768D1
Hydrogenovibrio sp. Milos-T1Hydrogenovibrio sp. Milos-T1
Bacteroidales bacterium KHT7Bacteroidales bacterium KHT7
Sutterella sp. CAG:397Sutterella sp. CAG:397
Phascolarctobacterium sp. CAG:266Phascolarctobacterium sp. CAG:266
Prevotella sp. CAG:255Prevotella sp. CAG:255
Bacteroides sp. CAG:754Bacteroides sp. CAG:754
Porphyromonas macacaePorphyromonas macacae
Alistipes sp. CAG:831Alistipes sp. CAG:831
Gabonia massiliensisGabonia massiliensis
Bacteroides sp. 14(A)Bacteroides sp. 14(A)
Virgibacillus salinusVirgibacillus salinus
Bacteroides sp. CAG:189Bacteroides sp. CAG:189
Chryseobacterium sp. Leaf404Chryseobacterium sp. Leaf404
Bacteroides ihuaeBacteroides ihuae
Bacteroides reticulotermitisBacteroides reticulotermitis
Prevotella sp. CAG:1320Prevotella sp. CAG:1320
Prevotella sp. khp7Prevotella sp. khp7
Sporomusa acidovoransSporomusa acidovorans
Polaribacter sp. Hel_I_88Polaribacter sp. Hel_I_88
Prevotella sp. RM4Prevotella sp. RM4
Prevotella sp. khp1Prevotella sp. khp1
Dysgonomonas sp. HGC4Dysgonomonas sp. HGC4
Prevotella sp. CAG:592Prevotella sp. CAG:592
Prevotella sp. HJM029Prevotella sp. HJM029
Candidatus Symbiothrix dinenymphaeCandidatus Symbiothrix dinenymphae
Prevotella sp. FD3004Prevotella sp. FD3004
Cellulophaga phage phiSTCellulophaga phage phiST
Bacteroidales bacterium KA00251Bacteroidales bacterium KA00251
Maribacter sp. MAR_2009_60Maribacter sp. MAR_2009_60
Denitrovibrio acetiphilusDenitrovibrio acetiphilus
Bacteroides neonatiBacteroides neonati
Algibacter lectusAlgibacter lectus
uncultured bacterium 2M03uncultured bacterium 2M03
Chryseobacterium sp. ERMR1:04Chryseobacterium sp. ERMR1:04
Geobacillus sp. 12AMOR1Geobacillus sp. 12AMOR1
Algoriphagus boritoleransAlgoriphagus boritolerans
Eubacterium sp. SB2Eubacterium sp. SB2
Prevotella sp. oral taxon 317Prevotella sp. oral taxon 317
Psychroflexus torquisPsychroflexus torquis
Pedobacter terraePedobacter terrae
Clostridiales bacterium oral taxon 876Clostridiales bacterium oral taxon 876
Scytonema milleiScytonema millei
Thermoanaerobacter siderophilusThermoanaerobacter siderophilus
Nitrospirae bacterium RBG_19FT_COMBO_42_15Nitrospirae bacterium RBG_19FT_COMBO_42_15
Succinispira mobilisSuccinispira mobilis
Gabonibacter massiliensisGabonibacter massiliensis
Verrucomicrobia bacterium SCGC AAA168-F10Verrucomicrobia bacterium SCGC AAA168-F10
Clostridia bacterium UC5.1-2H6Clostridia bacterium UC5.1-2H6
Bacillus phage BCP8-2Bacillus phage BCP8-2
Mucilaginibacter gotjawaliMucilaginibacter gotjawali
Aliarcobacter butzleriAliarcobacter butzleri
Prevotella sp. P5-125Prevotella sp. P5-125
Exiguobacterium sp. BMC-KPExiguobacterium sp. BMC-KP
Burkholderiales bacterium GJ-E10Burkholderiales bacterium GJ-E10
Bacteroides sp. HMSC068A09Bacteroides sp. HMSC068A09
Tannerella sp. CAG:118Tannerella sp. CAG:118
Myroides phaeusMyroides phaeus
Thiomonas sp. FB-6Thiomonas sp. FB-6
Saccharicrinis fermentansSaccharicrinis fermentans
Marinobacterium stanieriMarinobacterium stanieri
Sulfurovum sp. AS07-7Sulfurovum sp. AS07-7
Bacteroides sp. CAG:98Bacteroides sp. CAG:98
Capnocytophaga sp. oral taxon 332Capnocytophaga sp. oral taxon 332
Human mastadenovirus CHuman mastadenovirus C
Parabacteroides sp. D13Parabacteroides sp. D13
Bacillus sp. 17376Bacillus sp. 17376

Revision editor(s): AlishaM

Experiment 3


Needs review

Curated date: 2024/12/16

Curator: AlishaM

Revision editor(s): AlishaM

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Children with Autism Spectrum Disorder (ASD)
Group 0 sample size Number of subjects in the control (unexposed) group
143
Group 1 sample size Number of subjects in the case (exposed) group
143

Lab analysis

Statistical Analysis

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
No


Signature 1

Needs review

Curated date: 2024/12/16

Curator: AlishaM

Revision editor(s): AlishaM

Source: Table S3

Description: Operational taxonomic units with significantly different relative abundance between ASD and TD group.

Abundance in Group 1: increased abundance in Children with Autism Spectrum Disorder (ASD)

NCBI Quality ControlLinks
Megasphaera
Comamonas
unclassified Enterobacteriaceae
Anaerostipes
Ruminiclostridium 6Ruminiclostridium 6
Lachnospiraceae
Eubacterium xylanophilum
Lachnospiraceae NK4A136 groupLachnospiraceae NK4A136 group
Morganella
Christensenellaceae R-7 groupChristensenellaceae R-7 group
Ruminococcus 1Ruminococcus 1
Fusobacterium
Pseudobutyrivibrio
Prevotella 7Prevotella 7
Butyrivibrio
Escherichia-ShigellaEscherichia-Shigella
Haemophilus
Bacillus
Diaphorobacter
Granulicatella
Intestinibacter
Subdoligranulum
Porphyromonadaceae
Candidatus Gastranaerophilales
Lachnospiraceae ND3007 groupLachnospiraceae ND3007 group
Uruburuella
Bifidobacterium
Rikenellaceae RC9 gut groupRikenellaceae RC9 gut group
Eggerthella
Coprococcus 1Coprococcus 1
Ruminiclostridium
Collinsella
Ruminiclostridium 5Ruminiclostridium 5
Turicibacter
Cetobacterium
Coriobacteriaceae
Dorea
Lactobacillus
Ruminococcaceae UCG 009Ruminococcaceae UCG 009
Allisonella
Weissella
Ruminiclostridium 9Ruminiclostridium 9
Gemella
Coprococcus 2Coprococcus 2
Mitsuokella
Catenibacterium
Ruminococcaceae NK4A214 groupRuminococcaceae NK4A214 group
Eubacterium ventriosum
unclassified Sphingomonadaceae
Gordonibacter
Ezakiella

Revision editor(s): AlishaM

Signature 2

Needs review

Curated date: 2024/12/16

Curator: AlishaM

Revision editor(s): AlishaM

Source: Table S3

Description: Operational taxonomic units with significantly different relative abundance between ASD and TD group

Abundance in Group 1: decreased abundance in Children with Autism Spectrum Disorder (ASD)

NCBI Quality ControlLinks
Prevotella 9Prevotella 9
Alloprevotella
Thermus
Prevotellaceae
VulcaniibacteriumVulcaniibacterium
Prevotellaceae UCG-001Prevotellaceae UCG-001
Paraprevotella
Phascolarctobacterium
Lachnospira
unclassified Bacteroidales
Halomonas
Lachnospira eligens
Alistipes
[Ruminococcus] torques
Intestinimonas
Odoribacter
Megamonas
Christensenellaceae
Anoxybacillus
Rhodospirillaceae
KitasatosporaKitasatospora
unclassified Burkholderiales
Faecalibacterium
Bacteroidales
Lachnospiraceae UCG-004Lachnospiraceae UCG-004
Tyzzerella
Butyricimonas
Caproiciproducens
Tyzzerella 3Tyzzerella 3
Anaeroglobus
Holdemania
Brevibacillus
unclassified Eubacteriales
Acinetobacter
Flavonifractor
Oscillospira
Psychrobacter
unclassified Porphyromonadaceae
Erysipelotrichaceae UCG-004Erysipelotrichaceae UCG-004
Succiniclasticum
Stenotrophomonas

Revision editor(s): AlishaM

Experiment 4


Needs review

Curated date: 2024/12/16

Curator: AlishaM

Revision editor(s): AlishaM

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Children with non-constipated Autism Spectrum Disorder (NC-ASD)
Group 0 sample size Number of subjects in the control (unexposed) group
86
Group 1 sample size Number of subjects in the case (exposed) group
86

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2024/12/16

Curator: AlishaM

Revision editor(s): AlishaM

Source: Table S4

Description: Operational taxonomic units, phylum and genus with significantly different relative abundance between NC-ASD and TD group

Abundance in Group 1: increased abundance in Children with non-constipated Autism Spectrum Disorder (NC-ASD)

NCBI Quality ControlLinks
Anaerostipes
Bacillus
Butyricicoccus
Butyrivibrio
Candidatus Gastranaerophilales
Catenibacterium
Comamonas
Dorea
Eikenella
Eubacterium xylanophilum
Fusobacterium
Granulicatella
Haemophilus
Intestinibacter
Lachnoclostridium
Lachnospiraceae
Megasphaera
Morganella
Subdoligranulum
Turicibacter
Uruburuella
Weissella
unclassified Enterobacteriaceae
Ruminiclostridium 6Ruminiclostridium 6
Ruminococcus 2Ruminococcus 2
Ruminococcus 1Ruminococcus 1
Lachnospiraceae ND3007 groupLachnospiraceae ND3007 group
Lachnospiraceae NK4A136 groupLachnospiraceae NK4A136 group
Coprococcus 2Coprococcus 2
Rikenellaceae RC9 gut groupRikenellaceae RC9 gut group
Escherichia-ShigellaEscherichia-Shigella
Prevotella 7Prevotella 7
Ruminiclostridium 5Ruminiclostridium 5
Cyanobacteriota
Fusobacteriia
Pseudomonadota

Revision editor(s): AlishaM

Signature 2

Needs review

Curated date: 2024/12/16

Curator: AlishaM

Revision editor(s): AlishaM

Source: Table S4

Description: Operational taxonomic units, phylum and genus with significantly different relative abundance between NC-ASD and TD group

Abundance in Group 1: decreased abundance in Children with non-constipated Autism Spectrum Disorder (NC-ASD)

NCBI Quality ControlLinks
Parabacteroides
Alloprevotella
Prevotella_2Prevotella_2
Prevotella_9Prevotella_9
Lachnospira
VulcaniibacteriumVulcaniibacterium
Phascolarctobacterium
Thermus
Odoribacter
Prevotellaceae
Desulfovibrio
[Ruminococcus] torques
Alistipes
Dialister
Rhodospirillaceae
unclassified Bacteroidales
Halomonas
Paraprevotella
Megamonas
Butyricimonas
Parasutterella
Prevotellaceae NK3B31 groupPrevotellaceae NK3B31 group
Intestinimonas
Sellimonas
Roseburia
Oscillospira
Anoxybacillus
unclassified Burkholderiales
Tyzzerella
Slackia
Prevotellaceae UCG-001Prevotellaceae UCG-001
Lachnospiraceae UCG-004Lachnospiraceae UCG-004
unclassified Eubacteriales
KitasatosporaKitasatospora
Caproiciproducens
Hydrogenoanaerobacterium
Lachnospira eligens
Erysipelotrichaceae
Coprococcus 3Coprococcus 3
Stenotrophomonas
Ruminiclostridium 9Ruminiclostridium 9
Anaeroglobus
Peptoniphilus
Ruminococcaceae UCG-013Ruminococcaceae UCG-013
Prevotella
Deinococcus-ThermusDeinococcus-Thermus
Bacteroidia

Revision editor(s): AlishaM