Differences in fecal microbial metabolites and microbiota of children with autism spectrum disorders
Open accessAbstract
Evidence supporting that gut problems are linked to ASD symptoms has been accumulating both in humans and animal models of ASD. Gut microbes and their metabolites may be linked not only to GI problems but also to ASD behavior symptoms. Despite this high interest, most previous studies have looked mainly at microbial structure, and studies on fecal metabolites are rare in the context of ASD. Thus, we aimed to detect fecal metabolites that may be present at significantly different concentrations between 21 children with ASD and 23 neurotypical children and to investigate its possible link to human gut microbiome. Using 1 H-NMR spectroscopy and 16S rRNA gene amplicon sequencing, we examined metabolite profiles and microbial compositions in fecal samples, respectively. Of the 59 metabolites detected, isopropanol concentrations were significantly higher in feces of children with ASD after multiple testing corrections. We also observed similar trends of fecal metabolites to previous studies; children with ASD have higher fecal p-cresol and possibly lower GABA concentrations. In addition, Fisher Discriminant Analysis (FDA) with leave-out-validation suggested that a group of metabolites-caprate, nicotinate, glutamine, thymine, and aspartate-may potentially function as a modest biomarker to separate ASD participants from the neurotypical group (78% sensitivity and 81% specificity). Consistent with our previous Arizona cohort study, we also confirmed lower gut microbial diversity and reduced relative abundances of phylotypes most closely related to Prevotella copri in children with ASD. After multiple testing corrections, we also learned that relative abundances of Feacalibacterium prausnitzii and Haemophilus parainfluenzae were lower in feces of children with ASD. Despite a relatively short list of fecal metabolites, the data in this study support that children with ASD have altered metabolite profiles in feces when compared with neurotypical children and warrant further investigation of metabolites in larger cohorts.
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Independent studies have indicated a potential increase in the abundance of Collinsella, Eggerthella, Haemophilus, Klebsiella, and Phyllobacterium bacteria in the intestines of individuals diagnosed with ASD compared to the general population.
“Furthermore, the findings of independent studies have indicated a potential increase in the abundance of Collinsella, Eggerthella, Haemophilus, Klebsiella, and Phyllobacterium bacteria in the intestines of individuals diagnosed with ASD compared to the general population [18,102,104,111].”
From The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders (2025) · cites this paper as [102]
Scientific research on the genus Prevotella, including the species P. copri, yielded equivocal results.
“The scientific research on the genus Prevotella, including the species P. copri, yielded equivocal results [102,103,107,110,112,114,115].”
From The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders (2025) · cites this paper as [102]
The last three studies indicated decreases in alpha diversity, but the studies came from one laboratory.
“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 [41]
Among seven papers reporting beta diversity, four showed significant differences in beta diversity between ASD and SIB/HC while the rest did not.
“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 [41]
These seven Prevotella studies showed either a non-significant result in relative abundance or a lower relative abundance in children classified as ASD versus SIB or HC.
“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 [41]
Despite speculation that Sutterella was increased in children with ASD, this was not true in every study; three studies suggested no significant differences and one suggested a decrease.
“Despite speculation that Sutterella was increased in children with ASD [53, 55], this was not true in every study. There were three studies suggesting no significant differences [38, 41, 48] and one suggesting a decrease [44], but this particular study included adolescents in their cohort.”
From Gut microbiota changes in children with autism spectrum disorder: a systematic review (2020) · cites this paper as [41]
Streptococcus results (not S. thermophilus) corroborated an overall decrease in counts and percentage in ASD cases when statistical significance was reached.
“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 [41]
No specific findings were identified in the Verrucomicrobia phylum and in the Verrucomicrobiaceae family.
“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 [41]
Ten studies analyzed β-diversity, and six consistently reported that the microbiota of ASD patients clustered significantly apart from that of healthy controls.
“In this systematic review, ten studies analyzed β-diversity (unweighted UniFrac distance, weighted UniFrac distances, and Bray-Curtis), six of them consistently reported that the microbiota of ASD patients clustered significantly apart from that of HCs16–18,23,27.”
From Altered composition and function of intestinal microbiota in autism spectrum disorders: A systematic review (2019) · cites this paper as [16]
Of nine studies comparing α-diversity, three demonstrated a significant reduction in α-diversity in ASD patients.
“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 [16]
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- Authors
- Kang, D.-W., Ilhan, Z. E., Isern, N. G., Hoyt, D. W., Howsmon, D. P., Shaffer, M., Lozupone, C. A., Hahn, J., Adams, J. B., & Krajmalnik-Brown, R.
- Affiliations
- Arizona State University (US)
- Pacific Northwest National Laboratory (US)
- Rensselaer Polytechnic Institute (US)
- University of Colorado Anschutz (US)
- ORCID
- Venue
- Anaerobe
- Publisher
- Elsevier BV
- Published
- 2018-02
- Volume
- 49
- Pages
- 121-131
- ISSN
- 1075-9964 (ISSN-L)
- OpenAlex
- W2781422490
- Semantic Scholar
- bcac5fa4db6f53a2814669c41b83055e76cf4476
- Cited by
- 381
- References
- 93
- Citations by year
- 2026: 27 · 2025: 50 · 2024: 40 · 2023: 51 · 2022: 47 · 2021: 68 · 2020: 48 · 2019: 38 · 2018: 12
- FWCI
- 10.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 345 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Anaerobe (acceptedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- Funders
- BHARE (Brenen Hornstein Autism Research & Education) Foundation
- Emch Foundation
- Autism Research Institute
- 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 metabolites, gut microbiota, isopropanol, p-cresol, GABA, metabolomic biomarkers, Prevotella copri, Faecalibacterium prausnitzii, Haemophilus parainfluenzae, microbial diversity, children
- MeSH terms
- Autism Spectrum Disorder, Gastrointestinal Microbiome, Adolescent, Bacteria, Child, Child, Preschool, Feces, Female, Humans, Male, Cohort Studies, Biomarkers, Neurotransmitter Agents, 2-Propanol, Biodiversity
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