IMR Press / FBL / Volume 26 / Issue 12 / DOI: 10.52586/5051
Open Access Article
Sex-specific differences in the gut microbiota and fecal metabolites in an adolescent valproic acid-induced rat autism model
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1 Department of Pediatrics, Peking University People’s Hospital, 100044 Beijing, China
2 Department of Pediatrics, Peking University First Hospital, 100034 Beijing, China
3 Beijing Gutgene Technology Co. Ltd, 100085 Beijing, China

Academic Editor: Graham Pawelec

Front. Biosci. (Landmark Ed) 2021, 26(12), 1585–1598; https://doi.org/10.52586/5051
Submitted: 23 August 2021 | Revised: 23 September 2021 | Accepted: 30 October 2021 | Published: 30 December 2021
Copyright: © 2021 The Author(s). Published by BRI.
This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).
Abstract

Background: Alterations in the microbiota-gut-brain axis are associated with the onset of autism spectrum disorder (ASD). Numerous studies have reported that the gut microbiota (GM) is significantly altered in individuals with ASD and animal models of ASD. However, few studies have focused on sex-specific differences in the GM and fecal metabolites of ASD. Methods: In this study, we performed 16S rRNA gene sequencing and untargeted metabolomics in parallel on fecal samples from a valproic acid (VPA)-induced rat model of autism (VPA rats). Based on these data, we analyzed differentially abundant metabolites in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database to reveal the possible mechanism of ASD. Data derived from male and female rats were analyzed separately. Finally, we analyzed the correlation between characteristic genera and characteristic fecal metabolites in VPA rats of both sexes. Results: The results showed that VPA rats of both sexes presented remarkable alterations in the GM and fecal metabolites. Sex-specific differences were noticeably detected. We identified 51 annotated differentially abundant fecal metabolites and 1 differentially enriched KEGG pathway between the male VPA and male control groups. Ruminococcus_2, Candidatus_Soleaferrea, Desulfovibrio, Candidatus_Saccharimonas, Intestinimonas, [Eubacterium]_xylanophilum_group, [Eubacterium]_brachy_group and [Bacteroides]_pectinophilus_group were the characteristic genera of male VPA rats. Between the female VPA and female control groups, 124 annotated differentially abundant fecal metabolites were identified without differentially enriched KEGG pathways. Ruminiclostridium, Acetatifactor, Desulfovibrio, [Eubacterium]_xylanophilum_group and Candidatus_Saccharimonas were the characteristic genera of female VPA rats. Correlation analysis revealed a tight relationship between the GM and fecal metabolites in VPA rats of both sexes. Conclusions: In conclusion, alterations in the GM and fecal metabolites in VPA rats showed sex-specific differences. The therapy for ASD might be different between sexes in the future.

Keywords
Autism spectrum disorder
Valproic acid
Gut microbiota
Fecal metabolomics
Sex-specific differences
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