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Cited by 231Gut microbiota and healthAutism Spectrum Disorder ResearchGastrointestinal motility and disorders

Comparison of Fecal Microbiota in Children with Autism Spectrum Disorders and Neurotypical Siblings in the Simons Simplex Collection

Open access
Son, Joshua S., Zheng, Ling J., Rowehl, Leahana M., Tian, Xinyu, Zhang, Yuanhao, Zhu, Wei, Litcher-Kelly, Leighann, Gadow, Kenneth D. +5 more·2015·PLOS ONE
DOI 10.1371/journal.pone.0137725PMC PMC4591364
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Abstract

In order to assess potential associations between autism spectrum disorder (ASD) phenotype, functional GI disorders and fecal microbiota, we recruited simplex families, which had only a single ASD proband and neurotypical (NT) siblings, through the Simons Simplex Community at the Interactive Autism Network (SSC@IAN). Fecal samples and metadata related to functional GI disorders and diet were collected from ASD probands and NT siblings of ASD probands (age 7-14). Functional gastrointestinal disorders (FGID) were assessed using the parent-completed ROME III questionnaire for pediatric FGIDs, and problem behaviors were assessed using the Child Behavior Check List (CBCL). Targeted quantitative polymerase chain reaction (qPCR) assays were conducted on selected taxa implicated in ASD, including Sutterella spp., Bacteroidetes spp. and Prevotella spp. Illumina sequencing of the V1V2 and the V1V3 regions of the bacterial 16S rRNA genes from fecal DNA was performed to an average depth of 208,000 and 107,000 high-quality reads respectively. Twenty-five of 59 ASD children and 13 of 44 NT siblings met ROME III criteria for at least one FGID. Functional constipation was more prevalent in ASD (17 of 59) compared to NT siblings (6 of 44, P = 0.035). The mean CBCL scores in NT siblings with FGID, ASD children with FGID and ASD without FGID were comparably higher (58-62 vs. 44, P < 0.0001) when compared to NT children without FGID. There was no significant difference in macronutrient intake between ASD and NT siblings. There was no significant difference in ASD severity scores between ASD children with and without FGID. No significant difference in diversity or overall microbial composition was detected between ASD children with NT siblings. Exploratory analysis of the 16S rRNA sequencing data, however, identified several low abundance taxa binned at the genus level that were associated with ASD and/or first order ASD*FGID interactions (FDR <0.1).

AI snapshot

Written from the paper’s full text.

TL;DR

In simplex families from SSC@IAN, ASD children and their neurotypical siblings showed no significant difference in overall fecal microbial diversity or composition, but functional constipation was more common in ASD children. Exploratory 16S analyses found only low-abundance genus-level taxa associated with ASD and/or ASD*FGID interactions.

Key findings

  • Among 59 ASD children and 44 NT siblings from 66 families, 25/59 ASD children (42%) and 13/44 NT siblings (30%) met ROME III criteria for at least one FGID; functional constipation was more prevalent in ASD children (17/59) than NT siblings (6/44, P = 0.035).
  • Mean CBCL scores in NT siblings with FGID, ASD children with FGID, and ASD children without FGID were comparably higher than NT children without FGID (58–62 vs. 44, P < 0.0001); no significant difference in macronutrient intake was found between ASD and NT siblings, and ADOS-CSS did not differ significantly between ASD children with and without FGID.
  • No significant difference in α-diversity, β-diversity, or overall microbial composition was detected between ASD children and NT siblings; targeted qPCR showed no significant differences for Sutterella, Prevotella, Bacteroidetes, C. coccoides-E. rectales, Faecalibacterium prausnitzii, or Escherichia coli.
  • Exploratory 16S rRNA sequencing identified several low-abundance genus-level taxa associated with ASD and/or first-order ASD*FGID interactions at FDR < 0.1, including Cyanobacteria/Chloroplast, which was increased in the ASD-with-FGID group and appeared linked to chia seed consumption in two ASD children with functional constipation.

Methods

  • Families were recruited through the Simons Simplex Community at the Interactive Autism Network (SSC@IAN); of 245 potentially eligible families with 339 children, 107 families with 145 children consented and 66 families with 103 children completed the study. Participants were ASD probands and NT siblings aged 7–14, excluding those with GI disease, serious medical problems, or antibiotics within one month of stool collection.
  • Parents completed the ROME III questionnaire for pediatric FGIDs, the CBCL/6-18, and a one-week food diary; fecal samples underwent targeted qPCR for selected bacterial subgroups and Illumina sequencing of the V1V2 and V1V3 regions of bacterial 16S rRNA genes.
  • Analyses included Fisher exact tests, mixed-effect models with ASD, FGID, and ASD*FGID as fixed effects and family as random effect, α-diversity indices, PERMANOVA for β-diversity, and negative binomial/zero-inflated negative binomial models for individual OTUs with Benjamini-Hochberg FDR adjustment.

Limitations

  • The paper states that although this is one of the larger studies of its kind, the sample size is still modest given the number of variables included, and that additional ASD children, NT siblings (preferably family matched), and unrelated controls using the same phenotyping tools are needed to confirm the findings.
  • The paper states that it may be necessary to restrict dietary intake of plant-derived supplements such as chia seeds to determine whether the Cyanobacteria/Chloroplast signal is biologically significant for ASD pathophysiology.
  • Evident from the text: the study lacked unrelated NT controls, so it cannot distinguish whether NT siblings of ASD children have altered microbiomes relative to the general population; the significant microbial findings are exploratory, low-abundance, and not consistently replicated across V1V2 and V1V3 datasets.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1371/journal.pone.0137725

Cites

73 of 73 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 45 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    No significant difference in beta-diversity was noted between ASD and NT sibling bacterial communities at the phyla, family or genus level using Bray-Curtis, Jaccard or Morisita-Horn indices.

    “No significant difference (p < 0.05) was noted in β-diversity between ASD and NT sibling bacterial communities analyzed at the phyla, family or genus level and using Bray-Curtis, Jaccard or Morisita-Horn indices as dissimilarity measurements.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The study had adequate statistical power to detect differences in the microbial outcomes measured between ASD and NT siblings.
  • Findingown data

    There was no significant change in the prevalence of GI symptoms in ASD children between the previous SSC registry assessment and the current study assessment approximately 2-3 years later.

    “there was no significant change in the prevalence of the GI symptoms occurred over time.”
    • Also stated in: § Demographics and functional GI disorders (FGID) in ASD and NT siblings · plain
      “There was no significant change in the prevalence of any of the seven problematic GI symptoms in the ASD children at the two time points.”
    Quote in the paperNot a substantial claim
  • Findingown data

    The mean relative abundance of the Cyanobacteria/Chloroplast genus was increased in the ASD-with FGID group compared to the other three categories (ASD without FGID, NT siblings with FGID, and NT siblings without FGID).

    “The mean relative abundance of this genus was increased in the ASD-with FGID group compared to those of the other three categories (ASD without FGID, NT siblings with FGID and NT siblings without FGID, see S4 Table for mean relative abundances).”
    Quote in the paperNot a substantial claim
  • Findingown data

    No significant associations were detected between the relative abundance of the Sutterella or Prevotella genera and ASD, FGID or ASD*FGID first order interactions in either the V1V2 or V1V3 datasets.

    “No significant associations were detected between the relative abundance of the Sutterella or Prevotella genera and ASD, FGID or ASD*FGID first order interactions (see Table 6) in either the V1V2 or V1V3 datasets.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Inspection of the daily dietary logs of the ASD children with high counts of Chloroplast sequences revealed that these particular children were fed shakes containing chia seeds.

    “Inspection of the daily dietary logs of the ASD children with high counts of Chloroplast sequences revealed that these particular children were fed shakes containing chia seeds.”
    Quote in the paperSubstantial claim
  • May combine two claims. 11
  • Classified as probably not a substantial claim. 23

  • May combine two claims.

    Findingown data

    Comparisons of the relative abundances of the Bacteroidetes phylum, and the Sutterella and Prevotella genera reveal high correlations between MiSeq V1V2 and V1V3 (ρ≈0.9) and small proportional biases.

    “Comparisons of the relative abundances of the Bacteroidetes phylum, and the Sutterella and Prevotella genera reveal high correlations between MiSeq V1V2 and V1V3 (ρ≈0.9) and small proportional biases (S5 Table and S1 Fig).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    No significant effect of ASD, FGID or ASD*FGID was observed on OTU complexity or richness (Shannon diversity and Chao1) in the 16S rRNA data.

    “No significant effect of ASD, FGID or ASD*FGID was observed on OTU complexity or richness, two measures of α-diversity, Shannon diversity and Chao 1 (see Table 5for mean values).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The study had adequate statistical power to detect differences in the microbial outcomes measured between ASD and NT siblings.

  • May combine two claims.

    Findingown data

    Fifteen ASD children and 13 NT siblings in 37 families met ROME III criteria for at least one FGID, with concordance for FGIDs in 6 (18%) ASD/NT sibling pairs.

    “Fifteen ASD children and 13 NT siblings in 37 families met ROME III criteria for at least one FGID, with concordance for FGIDs in 6 (18%) ASD/NT sibling pairs.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingnone given

    None of the other subjects consumed chia seeds except one ASD child who ingested a serving of mixed grain bread that included chia grain.

    “None of the other subjects consumed chia seeds except one ASD child who ingested a serving of mixed grain bread that included chia grain.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Mean total, internalizing, externalizing and subscale CBCL scores were significantly increased in ASD children compared to NT children.

    “Mean total, internalizing, externalizing and subscale CBCL scores were significantly increased (p < 0.05) in the ASD children in both the ASD/NT sibling pairs and in comparison of all the ASD with NT children (matched and unmatched).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning

    While there were generally positively correlated measurements between the MiSeq and qPCR platforms, large systematic biases were observed particularly with the two relative low abundance genera, Sutterella and Provetella.

    “While there were generally positively correlated measurements between the MiSeq and qPCR platforms, we observed large systematic biases particularly with the two relative low abundance genera, Sutterella and Provetella.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Our study detected no differences in either α or β diversity between ASD and NT siblings.

    “Our study also detected no differences in either α or β diversity between ASD and NT siblings.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Phyla of lower abundance, including RF3, Tenericutes, Cyanobacteria, Verrucomicrobia, Lentisphaerae, and Fusobacterium, were detected.

    “Phyla of lower abundance, including RF3, Tenericutes, Cyanobacteria, Verrucomicrobia, Lentisphaerae, and Fusobacterium were also detected (see S3 Table).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    The Silva database used in the current study binned the Melainabacteria sequences in a taxon that was distinct from the Chloroplast taxon.

    “The Silva database used in the current study, however, binned the Melainabacteria sequences in a taxon that was distinct from the Chloroplast taxon.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    At the genus level, 359 operational taxonomic units (OTU) were detected for the V1V2 dataset and 189 OTUs for the V1-V3 datasets.

    “At the genus level, 359 operational taxonomic units (OTU) were detected for the V1V2 dataset and 189 OTUs for the V1-V3 datasets, respectively.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The CBCL/6-18 is a parent report form to screen for emotional, behavioral, and social problems in children ages 6-18.

    “The CBCL/6-18 is a parent report form to screen for emotional, behavioral, and social problems in children ages 6–18 [33].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [33] TM Achenbach, 2001

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    The failure to replicate previously reported differences may reflect the smaller number of subjects enrolled in the previous studies, possibly resulting in Type 1 errors.

    “This may reflect the smaller number of subjects enrolled in the previous studies, possibly resulting in Type 1 errors.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    The p-values for each OTU were adjusted for multiple comparisons to calculate a false discovery rate using the Benjamini-Hochberg procedure.

    “The p-values for each OTU were adjusted for multiple comparisons to calculate a false discovery rate (FDR) using the Benjamini-Hochberg procedure [59].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [59] Y Benjamini, 1995, Controlling the false discovery rate: a practical and powerful approach to multiple testing, J R Statist Soc B source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Studies tracking siblings of ASD children have detected vulnerabilities in some neurocognitive domains in the absence of an ASD diagnosis, suggesting that some NT siblings may exhibit a broader subclinical ASD phenotype.

    “Studies tracking siblings of ASD children have detected vulnerabilities in some neurocognitive domains in the absence of an ASD diagnosis [72] suggesting that some of the NT siblings may exhibit a broader subclinical ASD phenotype.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [72] M Wade, 2015, Using sibling designs to understand neurodevelopmental disorders: from genes and environments to prevention programming, Biomed Res Int source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationcitation

    An alternative explanation for why a study comparing ASD children with NT siblings did not replicate differences reported between ASD children with unrelated controls is that NT siblings of ASD children have altered microbiomes compared to unrelated children.

    “An alternative explanation for why a study comparing ASD children with NT siblings did not replicate differences reported between ASD children with unrelated controls, is that NT siblings of ASD children have altered microbiomes compared to that of unrelated children [24].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [24] R Krajmalnik-Brown, 2015, Gut bacteria in children with autism spectrum disorders: challenges and promise of studying how a complex community influences a complex disease, Microb Ecol Health Dis

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Plasmid quantification standards were prepared from representative clones of the target organisms to ensure qPCR assays were conducted within the linear range and with similar slopes.

    “Plasmid quantification standards were prepared from representative clones of the target organisms to insure that the assays were conducted within the linear range and with similar slopes.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    ROME III is the current international standard by which functional GI disorders are diagnosed and classified.

    “which is the current international standard by which functional GI disorders (FGID) are diagnosed and classified [24].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [24] R Krajmalnik-Brown, 2015, Gut bacteria in children with autism spectrum disorders: challenges and promise of studying how a complex community influences a complex disease, Microb Ecol Health Dis

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The qPCR assays were carried out in triplicate.

    “All assays were carried out in triplicate.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Previous epidemiological studies using the ROME III process to survey the prevalence of a child having at least one FGID in general pediatric clinics reported a prevalence of 2% and 16%, respectively.

    “Previous epidemiological studies using the ROME III process to survey the prevalence of a child having at least one FGID in general pediatric clinics reported a prevalence of 2% and 16%, respectively [73,74]”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [73] E Miele, 2004, Functional gastrointestinal disorders in children: an Italian prospective survey, Pediatrics source

      Not checked in the free run.

    • cites [74] GS Karabulut, 2013, The incidence of irritable bowel syndrome in children using the Rome III criteria and the effect of trimebutine treatment, J Neurogastroenterol Motil source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    One previous study used intestinal mucosal samples rather than fecal samples.

    “One study used intestinal mucosal [10] rather than fecal samples.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] BL Williams, 2012, Application of novel PCR-based methods for detection, quantitation, and phylogenetic characterization of Sutterella species in intestinal biopsy samples from children with autism and gastrointestinal disturbances, MBio source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    GI symptoms are more common in ASD children than in NT children.

    “Review of previous studies suggest that GI symptoms are more common in ASD children than in NT children, but these studies suffer from methodological differences in assessing GI symptoms [28–31].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [28] BO McElhanon, 2014, Gastrointestinal symptoms in autism spectrum disorder: a meta-analysis, Pediatrics source

      Not checked in the free run.

    • cites [29] EY Hsiao, 2014, Gastrointestinal issues in autism spectrum disorder, Harv Rev Psychiatry source

      Not checked in the free run.

    • cites [30] GT Furuta, 2012, Management of constipation in children and adolescents with autism spectrum disorders, Pediatrics source

      Not checked in the free run.

    • cites [31] P Gorrindo, 2012, Gastrointestinal dysfunction in autism: parental report, clinical evaluation, and associated factors, Autism Res source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Our assessment of GI symptoms differs from previous studies in that we used the international standard for assessing FGIDs in the general pediatric population.

    “Our assessment of GI symptoms differs from previous studies in that we used the international standard for assessing FGIDs in the general pediatric population.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Study design and conductnone given

    In this study, 16S rRNA sequencing using MiSeq was carried out to a greater depth than previous studies utilizing pyrosequencing.

    “In this study, 16S rRNA sequencing using MiSeq was carried out to a greater depth than previous studies utilizing pyrosequencing.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Of the 44 NT siblings, 37 were family matched to the ASD children in the study and the remaining seven were siblings of ASD children not in the current study.

    “Of the 44 NT siblings, 37 were family matched to the ASD children in the study and the remaining seven NT children were siblings of ASD children who were not in the current study, in some cases because the ASD child was older than 14 years of age.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Study design and conductreasoning

    Our sample size is still modest given the number of variables included.

    “Although this is one of the larger studies comparing ASD, FGID and the gut microbiota in ASD children and NT siblings, our sample size is still modest given the number of variables included.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The Actinobacteria/Mobiluncus genus has previously been associated with bacterial vaginosis.

    “The Actinobacteria/Mobiluncus genus has previously been associated with bacterial vaginosis [71].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [71] RF Lamont, 2011, The vaginal microbiome: new information about genital tract flora using molecular based techniques, BJOG source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The Firmicutes/Asteroleplasma genus appears to represent a group of uncultured wall-less mycobacterium-like organisms within the class Erysipelotrichia.

    “The Firmicutes/Asteroleplasma genus appears to represent a group of uncultured wall-less mycobacterium like organisms within the class Erysipelotrichia [69].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [69] JJ Davis, 2013, Genomes of the class Erysipelotrichia clarify the firmicute origin of the class Mollicutes, Int J Syst Evol Microbiol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The Proteobacteria/Thalassospira genus appears to represent alpha-proteobacteria present in bacterioplankton and a number of uncultivated organisms.

    “The Proteobacteria/Thalassospira genus appears to represent alpha-proteobacteria present in bacterioplankton and a number of uncultivated organisms [70].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [70] Q Lai, 2014, Multilocus sequence analysis for assessment of phylogenetic diversity and biogeography in Thalassospira bacteria from diverse marine environments, PLoS One source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Constipation has been previously recognized as a significant comorbidity in ASD children.

    “Constipation has been previously recognized as a significant comorbidity in ASD children [28–31].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [28] BO McElhanon, 2014, Gastrointestinal symptoms in autism spectrum disorder: a meta-analysis, Pediatrics source

      Not checked in the free run.

    • cites [29] EY Hsiao, 2014, Gastrointestinal issues in autism spectrum disorder, Harv Rev Psychiatry source

      Not checked in the free run.

    • cites [30] GT Furuta, 2012, Management of constipation in children and adolescents with autism spectrum disorders, Pediatrics source

      Not checked in the free run.

    • cites [31] P Gorrindo, 2012, Gastrointestinal dysfunction in autism: parental report, clinical evaluation, and associated factors, Autism Res source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Metagenomic studies have detected a novel nonphotosynthetic taxon termed "Melainabacteria" present in human gut flora that represents either a sibling phylum or a class within the Cyanobacteria phylum.

    “Metagenomic studies have detected a novel nonphotosynthetic taxa termed “Melainabacteria” present in human gut flora that represents either a sibling phylum or a class within the Cyanobacteria phylum [65,66].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [65] SC Di Rienzi, 2013, The human gut and groundwater harbor non-photosynthetic bacteria belonging to a new candidate phylum sibling to Cyanobacteria, Elife source

      Not checked in the free run.

    • cites [66] RM Soo, 2014, An expanded genomic representation of the phylum cyanobacteria, Genome Biol Evol source

      Not checked in the free run.

30 of 30

  • The paper relies on this without support.

    The 7-day parent-recorded food diary accurately estimates children's daily macronutrient intake.

    “The parents were asked to record the daily dietary intake of ASD and NT siblings on the Stony Brook University Medical Center Department of Pediatrics Food Diary/Calorie Count sheet for 7 days prior to the collection of the stool sample.”

  • The paper relies on this without support.

    The study had adequate statistical power to detect differences in the microbial outcomes measured between ASD and NT siblings.

    “No significant difference in diversity or overall microbial composition was detected between ASD children with NT siblings.”
    “No significant difference was observed for any of these bacterial subgroups in the 37 ASD/NT sibling pairs (see Methods).”

  • The paper relies on this without support.

    The study had adequate statistical power to detect differences in macronutrient intake between ASD and NT siblings.

    “There was no significant difference in macronutrient intake between ASD and NT siblings.”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Completed-study group counts conflict

    Major

    The methods say 66 ASD children and 37 NT siblings completed the study, while the results say 59 ASD children and 44 NT siblings completed it. Both descriptions total 103 children but assign seven children to different groups.

  • Diet-restriction total disagrees with Table 3

    Minor

    The four groups in Table 3 list 1, 3, 0, and 1 children on a gluten- or casein-free diet, totaling five rather than four.

    Reported 4 · recomputed 5

  • FGID concordance percentage uses the wrong denominator

    Minor

    Six of the 37 matched sibling pairs is 16.2%, not the reported 18%.

    Reported 18 · recomputed 16.216216

  • Matched NT sibling FGID count differs from Table 1

    Minor

    The results text says 13 matched NT siblings had an FGID, but Table 1 reports 12.

  • H1b and H1c diagnoses are reversed in Table 1

    Minor

    The results text identifies H1b as cyclic vomiting syndrome and H1c as aerophagia, while Table 1 assigns those labels the other way around.

5 of 5

Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. R Krajmalnik-Brown, 2015, Gut bacteria in children with autism spectrum disorders: challenges and promise of studying how a complex community influences a complex disease, Microb Ecol Health Dis, 26, 26914
  2. Y Rosseel, 2012, lavaanAn R package for structural equation modeling, JSS, 48, 1

Cited by

Sorted by citations

Related

Authors
Son, J. S., Zheng, L. J., Rowehl, L. M., Tian, X., Zhang, Y., Zhu, W., Litcher-Kelly, L., Gadow, K. D., Gathungu, G., Robertson, C. E., Ir, D., Frank, D. N., & Li, E.
Affiliations
  • Stony Brook University (US)
  • University of Colorado Anschutz (US)
Corresponding author
Li, Ellen
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2015-10-01
Volume
10
Issue
10
Pages
e0137725
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0137725
PMC
PMC4591364
OpenAlex
W1860290282
Cited by
229
References
73
Citations by year
2026: 9 · 2025: 17 · 2024: 23 · 2023: 17 · 2022: 18 · 2021: 29 · 2020: 29 · 2019: 33 · 2018: 24 · 2017: 13 · 2016: 14 · 2015: 1 · 2014: 1
FWCI
7.52
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Academic Commons (Stony Brook University) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • Simons Foundation
  • Simons Foundation Autism Research Initiative
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords
autism spectrum disorder, fecal microbiota, functional gastrointestinal disorders, constipation, siblings, gut microbiota, Sutterella, Bacteroidetes, Prevotella, child behavior problems, macronutrient intake, ASD severity, microbial taxa
MeSH terms
Autism Spectrum Disorder, Adolescent, Bacteria, Child, Diet, Feces, Female, Humans, Male, Phenotype, RNA, Ribosomal, 16S, Case-Control Studies, Siblings, Gastrointestinal Tract, Microbiota

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