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Fecal Microbiota and Metabolome of Children with Autism and Pervasive Developmental Disorder Not Otherwise Specified
Open accessAbstract
This study aimed at investigating the fecal microbiota and metabolome of children with Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) and autism (AD) in comparison to healthy children (HC). Bacterial tag-encoded FLX-titanium amplicon pyrosequencing (bTEFAP) of the 16S rDNA and 16S rRNA analyses were carried out to determine total bacteria (16S rDNA) and metabolically active bacteria (16S rRNA), respectively. The main bacterial phyla (Firmicutes, Bacteroidetes, Fusobacteria and Verrucomicrobia) significantly (P<0.05) changed among the three groups of children. As estimated by rarefaction, Chao and Shannon diversity index, the highest microbial diversity was found in AD children. Based on 16S-rRNA and culture-dependent data, Faecalibacterium and Ruminococcus were present at the highest level in fecal samples of PDD-NOS and HC children. Caloramator, Sarcina and Clostridium genera were the highest in AD children. Compared to HC, the composition of Lachnospiraceae family also differed in PDD-NOS and, especially, AD children. Except for Eubacterium siraeum, the lowest level of Eubacteriaceae was found on fecal samples of AD children. The level of Bacteroidetes genera and some Alistipes and Akkermansia species were almost the highest in PDD-NOS or AD children as well as almost all the identified Sutterellaceae and Enterobacteriaceae were the highest in AD. Compared to HC children, Bifidobacterium species decreased in AD. As shown by Canonical Discriminant Analysis of Principal Coordinates, the levels of free amino acids and volatile organic compounds of fecal samples were markedly affected in PDD-NOS and, especially, AD children. If the gut microbiota differences among AD and PDD-NOS and HC children are one of the concomitant causes or the consequence of autism, they may have implications regarding specific diagnostic test, and/or for treatment and prevention.
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In the citing paper
“Several studies found lower levels of fecal SCFA, including butyrate in feces of ASD children [53, 64], while a 2012 study found increased ammonia and SCFA including acetic, butyric, isobutyric, valeric, and isovaleric acids in ASD [61].”
From The Gut Microbiota and Dysbiosis in Autism Spectrum Disorders (2018) · cites this paper as [64]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Stool-based microbiome characterization in several cohorts identified specific genera that differed in ASD vs control subjects, but most previous studies conducted their analysis at higher taxonomic levels, with little published data at the genus or species (ie, OTU) level.22, 25, 26, 27”
From Distinct Microbiome-Neuroimmune Signatures Correlate With Functional Abdominal Pain in Children With Autism Spectrum Disorder (2017) · cites this paper as [26]
Experimental — accuracy not yet measuredIn the citing paper
“Cross-sectional studies comparing the gut microbiota composition between healthy and ASD individuals have revealed an altered microbiota profile in patients with ASD, with several studies reporting increased levels of Clostridium and Lactobacillus along with elevated levels of SCFAs, including propionic and butyric acid (Wang et al., 2012, 2013; De Angelis et al., 2013; Kang et al., 2013).”
From Microbiome–microglia connections via the gut–brain axis (2019) · cites this paper as De Angelis et al., 2013
In the citing paper
“Studies indicate that autistic children exhibit lower overall SCFA levels, with a particularly pronounced reduction in butyrate [50].”
From The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders (2025) · cites this paper as [50]
In the citing paper
“Furthermore, SCFAs cross the BBB and influence early brain development by regulating the production of serotonin and dopamine [50,52].”
From The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders (2025) · cites this paper as [50]
In the citing paper
“Additionally, SCFAs possess neuroprotective properties and, through epigenetic modifications, enhance memory formation and neural plasticity [49,50,55].”
From The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders (2025) · cites this paper as [50]
In the citing paper
“Moreover, an elevated abundance of Ruminococcaceae, Enterobacteriaceae, Pasteurellaceae, and Lachnospiraceae families has been observed in the digestive tract of individuals with ASD [8,50,52,96,97,98,101,105,110,111].”
From The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders (2025) · cites this paper as [50]
In the citing paper
“Studies has shown a significant increase in the prevalence of Clostridium bacteria in ASD patients compared to the general population [8,50,52,96,97,98,99,100,101,102,103,104,105,106,107,108,109].”
From The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders (2025) · cites this paper as [50]
In the citing paper
“Additionally, studies suggest a potential increase in the prevalence of Lactobacillus in the fecal samples of patients diagnosed with ASD [8,18,50,96,97,98,102,103,106,109,110,111].”
From The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders (2025) · cites this paper as [50]
In the citing paper
“Furthermore, the presence of Alistipes may be observed at elevated levels in patients diagnosed with ASD [50,89,96,97,98].”
From The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders (2025) · cites this paper as [50]
In the citing paper
“An increasing number of studies indicate that the population of Desulfovibrio could exhibit an increase in cases of ASD [50,96,97,98,103,106,107,109].”
From The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders (2025) · cites this paper as [50]
In the citing paper
“in both plasma (17) and feces (18), abnormal tryptophan metabolism has been reported in children with ASD”
In the citing paper
“which are fermentation end products of non-digested carbohydrates, act both in the brain via free fatty acid receptors FFAR2 and FFAR3, and in the gut.In the brain, they have an impact on the production of neurotransmitters and catecholamines [280,282] and partially they affect the reward system, synaptic plasticity, and memory formation [286,287].In the intestine, they influence water and”
From The Role of Microbiota-Gut-Brain Axis in Neuropsychiatric and Neurological Disorders (2021) · cites this paper as [280]
In the citing paper
“Some studies found increased diversity of the microbiota in ASD [47, 64], whereas other studies show the opposite trend towards decreased diversity and richness [73, 74], or no differences in diversity [75, 77].”
From The Gut Microbiota and Dysbiosis in Autism Spectrum Disorders (2018) · cites this paper as [64]
In the citing paper
“metabolomic analyses of serum, feces, and urine from ASD subjects have uncovered differences in various molecules compared to TD individuals, with many dysregulated compounds being of microbial origin (De Angelis et al., 2013; Kang et al., 2017a; Ming et al., 2012; Mussap et al., 2016; Wang et al., 2019).”
From Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice (2019) · cites this paper as De Angelis et al., 2013
In the citing paper
“Gut bacterial communities differ between individuals with ASD and typically-developing (TD) controls (Coretti et al., 2018; De Angelis et al., 2013; Finegold et al., 2010; Gondalia et al., 2012; Kang et al., 2013, 2017a; Kushak et al., 2016; Liu et al., 2019; Son et al., 2015; Strati et al., 2017; Wang et al., 2019; Williams et al., 2011)”
From Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice (2019) · cites this paper as De Angelis et al., 2013
In the citing paper
“There were higher concentrations of amino acids in colon contents of oASD mice, similar to reports studying individuals with ASD (De Angelis et al., 2013).”
From Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice (2019) · cites this paper as De Angelis et al., 2013
In the citing paper
“Since then numerous studies from diverse cohorts have reported that microbiome profiles of ASD individuals, especially those with co-morbid GI dysfunction, differ from that of TD controls (Coretti et al., 2018; De Angelis et al., 2013; Finegold et al., 2010; Gondalia et al., 2012; Kang et al., 2013, 2017a; Kushak et al., 2016; Liu et al., 2019; Son et al., 2015; Strati et al., 2017; Wang et al., 2”
From Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice (2019) · cites this paper as De Angelis et al., 2013
In the citing paper
“Two studies showed increases [31, 33] and six studies showed no significant changes in alpha diversity [36, 42, 43, 48, 50, 54].”
From Gut microbiota changes in children with autism spectrum disorder: a systematic review (2020) · cites this paper as [31]
In the citing paper
“The rest of the studies observed either a decrease in Bacteroidetes percentage [50, 54] or no significant differences between cases and controls [31, 36, 48].”
From Gut microbiota changes in children with autism spectrum disorder: a systematic review (2020) · cites this paper as [31]
In the citing paper
“Among the seven [31, 36, 40–42, 48, 50] papers that reported on beta diversity, four [31, 40, 41, 50] papers showed significant differences in beta diversity between ASD and SIB/HC while the rest did not (Additional file 1: Table S2).”
From Gut microbiota changes in children with autism spectrum disorder: a systematic review (2020) · cites this paper as [31]
In the citing paper
“At the phylum level, none of the six studies showed an increase in absolute or relative abundance [31, 33, 36, 48, 51, 54].”
From Gut microbiota changes in children with autism spectrum disorder: a systematic review (2020) · cites this paper as [31]
In the citing paper
“Instead, these seven studies showed either a non-significant result in relative abundance [41, 48, 50, 52] or a lower relative abundance in children classified as ASD versus SIB or HC [31, 39, 42].”
From Gut microbiota changes in children with autism spectrum disorder: a systematic review (2020) · cites this paper as [31]
In the citing paper
“For relative abundance in both total and metabolically active Firmicutes, the studies demonstrated either a decrease [31, 33, 36] or no significant differences between children with ASD, SIB, and HC [48, 51, 54].”
From Gut microbiota changes in children with autism spectrum disorder: a systematic review (2020) · cites this paper as [31]
In the citing paper
“The general trend, however, supports no alterations in E. coli for children in ASD in five studies [30, 35, 42, 48, 52] vs one study [31] documenting a decrease in E. coli percentage among other microbiota.”
From Gut microbiota changes in children with autism spectrum disorder: a systematic review (2020) · cites this paper as [31]
In the citing paper
“In the order Lactobacillales and family Streptococcaceae, Streptococcus results (not S. thermophilus) corroborated an overall decrease in counts and percentage in ASD cases when statistical significance was reached [30, 31, 33, 37, 41].”
From Gut microbiota changes in children with autism spectrum disorder: a systematic review (2020) · cites this paper as [31]
In the citing paper
“No specific findings were identified in the Verrucomicrobia phylum [31, 33, 36, 39, 48] and in the Verrucomicrobiaceae family [31, 37, 39, 41, 52].”
From Gut microbiota changes in children with autism spectrum disorder: a systematic review (2020) · cites this paper as [31]
In the citing paper
“however, upon a closer look at Bifidobacterium, consistently lower counts and proportions were found in children with ASD versus their siblings [31, 52] or controls [30, 38, 47].”
From Gut microbiota changes in children with autism spectrum disorder: a systematic review (2020) · cites this paper as [31]
In the citing paper
“This study did not replicate previously reported differences in the relative abundances of bacterial categories, including the Bacteroidetes phylum [12–14], the Sutterella genus [7,8,10] and the Prevotella genus [11] between ASD and unrelated control children.”
From Comparison of Fecal Microbiota in Children with Autism Spectrum Disorders and Neurotypical Siblings in the Simons Simplex Collection (2015) · cites this paper as [13]
In the citing paper
“Of note, previous studies [6–8,12,14], with the exception of one study [13], failed to detect differences in microbial composition between ASD and NT siblings [11].”
From Comparison of Fecal Microbiota in Children with Autism Spectrum Disorders and Neurotypical Siblings in the Simons Simplex Collection (2015) · cites this paper as [13]
In the citing paper
“Stool-based microbiome characterization in several cohorts identified specific genera that differed in ASD vs control subjects, but most previous studies conducted their analysis at higher taxonomic levels, with little published data at the genus or species (ie, OTU) level.22, 25, 26, 27”
From Distinct Microbiome-Neuroimmune Signatures Correlate With Functional Abdominal Pain in Children With Autism Spectrum Disorder (2017) · cites this paper as [26]
In the citing paper
“others show the opposite result (De Angelis et al., 2013; Zhang et al., 2018)”
From Mechanisms underlying microbial-mediated changes in social behavior in mouse models of autism spectrum disorder (2019) · cites this paper as De Angelis et al., 2013
In the citing paper
“Many ASD children have also been shown to carry abnormalities in GI physiology, including: increased intestinal permeability [34,35], overall microbiota alterations [36,37,38,39,40], and gut infection with cresol-producing Clostridium difficile [39,41,42,43,44].”
From Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions (2019) · cites this paper as [36]
In the citing paper
“Indeed, some studies have revealed significant reductions in the relative abundance of Prevotella, Coprococcus, Enterococcus, Lactobacillus, Streptococcus, Lactococcus, Staphylococcus, Ruminococcus, and Bifidobacterium species in children with ASD compared with healthy controls [36,128,143].”
From Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions (2019) · cites this paper as [36]
In the citing paper
“Several studies on ASD have showed changes in the composition of the microbiota, particularly in the relative abundance of the mains gut bacterial phyla [36,37,143,144].”
From Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions (2019) · cites this paper as [36]
In the citing paper
“Others studies observed, in ASD children, high abundance of: Akkermansia muciniphilia, [36,143,148] Desulfovibrio, [37] and Faecalibacterium prausnitzii [36].”
From Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions (2019) · cites this paper as [36]
In the citing paper
“Moreover, ASD patients seem to be characterized by both elevated levels of SCFA concentrations in stool and serum, and increased level of SCFA-producing bacteria (e.g., Clostridia, Desulfovibrio, and Bacteroides) [29,36,180].”
From Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions (2019) · cites this paper as [36]
In the citing paper
“Decreased levels of Bifidobacterium and metabolites of free amino acids and short-chain fatty acids (SCFA) in the feces may also contribute to the development of ASD (23).”
From Association Between Gut Microbiota and Autism Spectrum Disorder: A Systematic Review and Meta-Analysis (2019) · cites this paper as [23]
In the citing paper
“In our meta-analysis, only two studies enrolled children with ASD who had no GI symptoms (23, 37), and one study did not provide details about GI symptoms (33).”
From Association Between Gut Microbiota and Autism Spectrum Disorder: A Systematic Review and Meta-Analysis (2019) · cites this paper as [23]
In the citing paper
“In addition, GI microbial dysbiosis, an imbalance in the organisms that make up the gut microbiota, has been documented in multiple studies of children with ASD [5, 7–14].”
From Pilot study of probiotic/colostrum supplementation on gut function in children with autism and gastrointestinal symptoms (2019) · cites this paper as [14]
In the citing paper
“Most studies demonstrate that children with ASD have more bacterial diversity [10, 14] and possess lower overall abundance of potentially beneficial taxa, such as Bifidobacterium and Akkermansia, [5, 10, 11], although some populations appear to differ from this trend [10, 13].”
From Pilot study of probiotic/colostrum supplementation on gut function in children with autism and gastrointestinal symptoms (2019) · cites this paper as [14]
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Metadata
- Authors
- De Angelis, M., Piccolo, M., Vannini, L., Siragusa, S., De Giacomo, A., Serrazzanetti, D. I., Cristofori, F., Guerzoni, M. E., Gobbetti, M., & Francavilla, R.
- Affiliations
- University of Bologna (IT)
- University of Bari Aldo Moro (IT)
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-10-09
- Volume
- 8
- Issue
- 10
- Pages
- e76993
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3793965
- OpenAlex
- W2144133378
- Cited by
- 887
- References
- 83
- Citations by year
- 2026: 43 · 2025: 68 · 2024: 69 · 2023: 104 · 2022: 98 · 2021: 125 · 2020: 85 · 2019: 76 · 2018: 70 · 2017: 35 · 2016: 52 · 2015: 37 · 2014: 23 · 2013: 1
- FWCI
- 16.86
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion)
- Open Research (University of Surrey) (submittedVersion, other-oa)
- 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, pervasive developmental disorder not otherwise specified, gut microbiota, fecal metabolome, children, microbial diversity, Firmicutes, Bacteroidetes, Faecalibacterium, Ruminococcus, Lachnospiraceae, Akkermansia, Bifidobacterium, free amino acids, volatile organic compounds, 16S rRNA, 16S rRNA gene
- MeSH terms
- Amino Acids, Autistic Disorder, Bacteria, Child, Child Development Disorders, Pervasive, Child, Preschool, Feces, Female, Humans, Male, Sequence Analysis, Metabolome, Volatile Organic Compounds, Microbiota
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