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Reduced Incidence of Prevotella and Other Fermenters in Intestinal Microflora of Autistic Children
Open accessAbstract
High proportions of autistic children suffer from gastrointestinal (GI) disorders, implying a link between autism and abnormalities in gut microbial functions. Increasing evidence from recent high-throughput sequencing analyses indicates that disturbances in composition and diversity of gut microbiome are associated with various disease conditions. However, microbiome-level studies on autism are limited and mostly focused on pathogenic bacteria. Therefore, here we aimed to define systemic changes in gut microbiome associated with autism and autism-related GI problems. We recruited 20 neurotypical and 20 autistic children accompanied by a survey of both autistic severity and GI symptoms. By pyrosequencing the V2/V3 regions in bacterial 16S rDNA from fecal DNA samples, we compared gut microbiomes of GI symptom-free neurotypical children with those of autistic children mostly presenting GI symptoms. Unexpectedly, the presence of autistic symptoms, rather than the severity of GI symptoms, was associated with less diverse gut microbiomes. Further, rigorous statistical tests with multiple testing corrections showed significantly lower abundances of the genera Prevotella, Coprococcus, and unclassified Veillonellaceae in autistic samples. These are intriguingly versatile carbohydrate-degrading and/or fermenting bacteria, suggesting a potential influence of unusual diet patterns observed in autistic children. However, multivariate analyses showed that autism-related changes in both overall diversity and individual genus abundances were correlated with the presence of autistic symptoms but not with their diet patterns. Taken together, autism and accompanying GI symptoms were characterized by distinct and less diverse gut microbial compositions with lower levels of Prevotella, Coprococcus, and unclassified Veillonellaceae.
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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 [25]
Checked by a reasoning model — may be wrong.
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
“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 Kang et al., 2013
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
“In the case of impaired BBB, which can be observed in certain (but not all) autistic subjects [37,254], LPS or SCFAs may cause brain inflammation and thus, further facilitate access to the brain for harmful substances, like heavy metals, that can accumulate there [228,246,255].”
From The Role of Microbiota-Gut-Brain Axis in Neuropsychiatric and Neurological Disorders (2021) · cites this paper as [228]
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
“Among them, three studies18,19,22 indicated the functional modules of gut microbiota in ASD patients were substantially different from that in HCs (Fig. 2).”
From Altered composition and function of intestinal microbiota in autism spectrum disorders: A systematic review (2019) · cites this paper as [22]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“In two studies of Kang et al. (Figs. 2b, c)19,22, the pathways of “Cell Motility”, “Cellular Processes” and “Bacterial motility proteins” had consistent significant discriminative power in HCs. In addition, “Bacterial chemotaxis” and “Flagellar assembly” were also noted.”
From Altered composition and function of intestinal microbiota in autism spectrum disorders: A systematic review (2019) · cites this paper as [22]
Experimental — accuracy not yet measured
In the citing paper
“Nevertheless, reduced bacterial diversity and increased biomass were reported in individuals with ASD [228,230].”
From The Role of Microbiota-Gut-Brain Axis in Neuropsychiatric and Neurological Disorders (2021) · cites this paper as [228]
In the citing paper
“The most important may be reduced amounts of Prevotella, Corprococcus, and Veilonellaceae (participating in carbohydrate ingestion and fermentation), Bacteroidetes, Actinobacteria, Proteobacteria [228]”
From The Role of Microbiota-Gut-Brain Axis in Neuropsychiatric and Neurological Disorders (2021) · cites this paper as [228]
In the citing paper
“The last three studies indicated decreases; however, the studies came from one laboratory [39–41].”
From Gut microbiota changes in children with autism spectrum disorder: a systematic review (2020) · cites this paper as [39]
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 [39]
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 [39]
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 [11]
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 [11]
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 [25]
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 [143]
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 [143]
In the citing paper
“In the scientific literature, some studies highlight a higher abundance of Clostridia and Desulfovibrio bacteria and a lower ratio of Bacteroidetes to Firmicutes in ASD [37,39,143,145].”
From Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions (2019) · cites this paper as [143]
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 [143]
In the citing paper
“Of the nine studies compared α-diversity, three studies demonstrated that α-diversity has a significant reduction in ASD patients16,19,22.”
From Altered composition and function of intestinal microbiota in autism spectrum disorders: A systematic review (2019) · cites this paper as [22]
In the citing paper
“Two sequencing studies reported that the abundance of Akkermansia was elevated in ASD patients22,23. Inconsistently, one qPCR study30 indicated that lower amount of Akkermansia muciniphila was found in feces of ASD patients than HCs.”
From Altered composition and function of intestinal microbiota in autism spectrum disorders: A systematic review (2019) · cites this paper as [22]
In the citing paper
“It should be noted that pathways of “Huntingtons disease” and “Amyotrophic lateral sclerosis (ALS)” under Neurodegenerative Diseases category as well as “Glutamatergic synapse” under Nervous System category were also increased in ASD patients.”
From Altered composition and function of intestinal microbiota in autism spectrum disorders: A systematic review (2019) · cites this paper as [22]
In the citing paper
“In ASD patients, the functional modules of metabolism were higher than that in HCs, such as “Oxidative phosphorylation” under Energy Metabolism category and “Glycine, serine and threonine metabolism” under Amino Acid Metabolism.”
From Altered composition and function of intestinal microbiota in autism spectrum disorders: A systematic review (2019) · cites this paper as [22]
In the citing paper
“Whereas, in ASD patients, the most enhanced functional module of microbiota was metabolism, including amino acid metabolism, lipid metabolism, carbohydrate metabolism, energy metabolism, cofactors and vitamins metabolism and tetracycline biosynthesis.”
From Altered composition and function of intestinal microbiota in autism spectrum disorders: A systematic review (2019) · cites this paper as [22]
In the citing paper
“Akkermansia and Ruminococcus are mucin-degrading bacterium and associated with the gut permeability59,60.”
From Altered composition and function of intestinal microbiota in autism spectrum disorders: A systematic review (2019) · cites this paper as [59]
In the citing paper
“Moreover, some functional modules involved in neurodegenerative diseases in human, such as Huntington disease and ALS were also raised in ASD patients.”
From Altered composition and function of intestinal microbiota in autism spectrum disorders: A systematic review (2019) · cites this paper as [22]
In the citing paper
“Functions of xenobiotics degradation such as toluene, aminobenzoate, polycyclic aromatic hydrocarbon, and bisphenol were also enhanced.”
From Altered composition and function of intestinal microbiota in autism spectrum disorders: A systematic review (2019) · cites this paper as [22]
In the citing paper
“In two accordant studies19,22, functional modules of microbiota in HCs mostly involved in cell motility, cellular processes, bacterial motility proteins, bacterial chemotaxis, and flagellar assembly, which indicated the basic physiological maintenance under normal condition.”
From Altered composition and function of intestinal microbiota in autism spectrum disorders: A systematic review (2019) · cites this paper as [22]
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 [13]
In the citing paper
“However, other studies have shown that Akkermansia levels are higher in children with ASD compared to typically developing children, although species-level composition was not examined [13].”
From Pilot study of probiotic/colostrum supplementation on gut function in children with autism and gastrointestinal symptoms (2019) · cites this paper as [13]
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Metadata
- Authors
- Kang, D.-W., Park, J. G., Ilhan, Z. E., Wallstrom, G., LaBaer, J., Adams, J. B., & Krajmalnik-Brown, R.
- Affiliations
- Arizona State University (US)
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-07-03
- Volume
- 8
- Issue
- 7
- Pages
- e68322
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3700858
- OpenAlex
- W2149756110
- Cited by
- 976
- References
- 71
- Citations by year
- 2026: 36 · 2025: 75 · 2024: 65 · 2023: 94 · 2022: 83 · 2021: 114 · 2020: 85 · 2019: 100 · 2018: 94 · 2017: 53 · 2016: 74 · 2015: 49 · 2014: 39 · 2013: 14
- FWCI
- 26.30
- 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)
- Figshare (submittedVersion, cc-by)
- Arizona State University Library Digital Repository (Arizona State University) (submittedVersion, cc-by)
- HAL (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Autism Research Institute
- National Institutes of Health
- 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, gut microbiota, gastrointestinal symptoms, Prevotella, Coprococcus, Veillonellaceae, microbial diversity, autism severity, diet patterns, fecal microbiota, children
- MeSH terms
- Adolescent, Autistic Disorder, Child, Child, Preschool, Female, Gastrointestinal Diseases, Humans, Male, Phylogeny, ROC Curve, Incidence, Cluster Analysis, Bacteroidaceae Infections, Prevotella, Gastrointestinal Tract, Biodiversity, Metagenome, Microbiota
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