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Peer-reviewedCC BY 4.0Frontiers in Immunology

Microbial intervention on germ-free zebrafish (Danio rerio) developmental delay and gut-brain axis hormones disturbance from innate to adaptive immune stages

  1. 1College of Public Health, Chongqing Medical University
  2. 2Science and Technology Industry Development Center, Chongqing Medical and Pharmaceutical College

Abstract

Introduction: The gut microbiota is associated with host development and endocrine signaling, but its role in early zebrafish development remains incompletely understood. Germ-free (GF) fish models are powerful tools to reveal the functions of intestinal microbiota and special strains.

Methods: This study generated and identified different models of conventionally raised (CR) fish, fish recolonized with a conventional microbial community (ex-GF), and GF fish infected with Aeromo nas sp. (GF-A) or Vibrio sp. (GF-V).

Results: The delayed development indexes assessed at 7 and 14 days-post fertilization (dpf) showed an obviously weaker behavior ability of GF fish without microbiota. Moreover, the histopathological characteristics indicated defects in intestinal morphology, fewer goblet cells, and ultrastructural abnor-malities using H&E and AB-PAS stains and ultra-structure by TEM analyses. The transcriptomic profile and gut microbiota also revealed differentially expressed genes (DEGs) and the dominant genera of GF or ex-GF larvae and juveniles, with the most impacted pathways being immune and cell regulation. Related hormones, short-chain fatty acid concentrations, and key genes were detected and disruption was exhibited by the absence or recolonization of gut microbiota or infection of special bacterial strains. Transcriptomic, microbial, and endocrine alterations differed among groups. Selected phenotypes were partially improved with stage-dependent restructuring but did not completely resemble CR states across all endpoints. The correlation analysis indicated the close relationship between developmental delay and microbiota depletion, behavior, hormone contents, and key genes in regulating pathways.

Conclusion: These findings demonstrate that microbial intervention contributes to early development of zebrafish, which may correlate with the gut-brain axis hormones. Thus, it contributes to the understanding of the roles of microbiota for diverse life stages and contributes to the development of microbial therapies in future.

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BibTeX
@article{zhang2026microbial,
  title = {{Microbial intervention on germ-free zebrafish (Danio rerio) developmental delay and gut-brain axis hormones disturbance from innate to adaptive immune stages}},
  author = {Lan-Chen Zhang and Hao-Yu Yang and Jin-Qiu Jia and Xiao-Bing Li and Jia-Xin He and Ying Tang and Yi-Wei Tang and Pan-Pan Jia},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1930616},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1930616/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Microbial intervention on germ-free zebrafish (Danio rerio) developmental delay and gut-brain axis hormones disturbance from innate to adaptive immune stages
AU  - Lan-Chen Zhang
AU  - Hao-Yu Yang
AU  - Jin-Qiu Jia
AU  - Xiao-Bing Li
AU  - Jia-Xin He
AU  - Ying Tang
AU  - Yi-Wei Tang
AU  - Pan-Pan Jia
PY  - 2026
DA  - 2026/10/19
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1930616
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1930616/full
AB  - Introduction: The gut microbiota is associated with host development and endocrine signaling, but its role in early zebrafish development remains incompletely understood. Germ-free (GF) fish models are powerful tools to reveal the functions of intestinal microbiota and special strains.  Methods: This study generated and identified different models of conventionally raised (CR) fish, fish recolonized with a conventional microbial community (ex-GF), and GF fish infected with Aeromo nas sp. (GF-A) or Vibrio sp. (GF-V).  Results: The delayed development indexes assessed at 7 and 14 days-post fertilization (dpf) showed an obviously weaker behavior ability of GF fish without microbiota. Moreover, the histopathological characteristics indicated defects in intestinal morphology, fewer goblet cells, and ultrastructural abnor-malities using H&E and AB-PAS stains and ultra-structure by TEM analyses. The transcriptomic profile and gut microbiota also revealed differentially expressed genes (DEGs) and the dominant genera of GF or ex-GF larvae and juveniles, with the most impacted pathways being immune and cell regulation. Related hormones, short-chain fatty acid concentrations, and key genes were detected and disruption was exhibited by the absence or recolonization of gut microbiota or infection of special bacterial strains. Transcriptomic, microbial, and endocrine alterations differed among groups. Selected phenotypes were partially improved with stage-dependent restructuring but did not completely resemble CR states across all endpoints. The correlation analysis indicated the close relationship between developmental delay and microbiota depletion, behavior, hormone contents, and key genes in regulating pathways.  Conclusion: These findings demonstrate that microbial intervention contributes to early development of zebrafish, which may correlate with the gut-brain axis hormones. Thus, it contributes to the understanding of the roles of microbiota for diverse life stages and contributes to the development of microbial therapies in future.
SN  - 1664-3224
ER  -