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A pilot study to investigate the alteration of gut microbial profile in Dip2a knockout mice


Accumulating evidence has pointed out that the gut-brain axis plays important roles in the etiology of autism spectrum disorder (ASD). Gut dysbiosis was reported in both ASD human patients and animal models. Dip2a was identified as a human ASD candidate gene. Deletion of Dip2a led to dendritic spine dysfunction and autistic-like behaviors in mice. To further investigate if Dip2a deletion leads to gut dysbiosis, we used 16S rDNA sequencing to study the gut microbiota in Dip2a KO mice. In both co-housed and separated breeding conditions, deletion of Dip2a could affect the gut microbiome composition. The probiotic bacteria, Lactobacillus and Bifidobacterium, became less abundant, while some potentially harmful bacteria, Alistipes, Lachnospiraceae_NK4A136_group, Clostridium, Desulfovibrio, and Enterorhabdus, became more abundant. We further found that probiotic treatment could help to reconstitute the gut microbiome composition in Dip2a KO mice. Altogether, these data showed DIP2A is required for the proper composition of gut microbiota, and the probiotics have potential roles in rectifying the gut microbiota in Dip2a KO mice.

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This work was supported by the National Natural Science Foundation of China (31871040 and 32070809), the Jilin Science and Technology department (20191008009TC), and the Fundamental Research Funds for the Central Universities (2412019FZ025 and 2412019FZ027).The sponsors had no role in the design, execution, interpretation, or writing of the study.

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Conceptualization, X.H. and S.L.; methodology and validation, Y.Z., Y.Q., J.Y., and J.L; writing (original draft preparation), X.H. and Y.Z.; writing (review and editing), S.L. and X.H.; funding acquisition, X.H.

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Correspondence to Shengnan Li or Xiaoxiao He.

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All mice used in this study were handled in accordance with the guidelines of the Institutional Animal Care and Use Committee of Northeast Normal University, China (NENU/IACUC, AP20151009).

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The authors declare no competing interests.

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Zhang, Y., Qu, Y., Yang, J. et al. A pilot study to investigate the alteration of gut microbial profile in Dip2a knockout mice. Int Microbiol 25, 267–274 (2022).

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  • Autism spectrum disorder
  • Dip2a
  • Gut-brain axis
  • Gut microbiota
  • Probiotic
  • 16 s rDNA