The microbiota and T cells non-genetically modulate inherited phenotypes transgenerationally

• DOI: 10.1016/j.celrep.2024.114029
• Publication Date: 2024-04-04T02:03:17Z
• Authors: Jordan C. Harris; Natalie A. Trigg; Bruktawit Goshu; Yuichi Yokoyama; Lenka Dohnalová; Ellen K. White; Adele Harman; Sofía M. Murga-Ga...; Jamie Ting-Chun Pan; Preeti Bhanap; Christoph A. Thaiss; Elizabeth A. Grice; Colin C. Conine; Taku Kambayashi
• Keywords: Male; 0301 basic medicine; 0303 health sciences; QH301-705.5; T-Lymphocytes; Microbiota; CP: Microbiology; CP: Immunology; Article; Mice, Inbred C57BL; Mice; Phenotype; Animals; Female; Biology (General)

The host-microbiota relationship has evolved to shape mammalian physiology, including immunity, metabolism, and development. Germ-free models are widely used to study microbial effects on host processes such as immunity. Here, we find that both germ-free and T cell-deficient mice exhibit a robust sebum secretion defect persisting across multiple generations despite microbial colonization and T cell repletion. These phenotypes are inherited by progeny conceived during in vitro fertilization using germ-free sperm and eggs, demonstrating that non-genetic information in the gametes is required for microbial-dependent phenotypic transmission. Accordingly, gene expression in early embryos derived from gametes from germ-free or T cell-deficient mice is strikingly and similarly altered. Our findings demonstrate that microbial- and immune-dependent regulation of non-genetic information in the gametes can transmit inherited phenotypes transgenerationally in mice. This mechanism could rapidly generate phenotypic diversity to enhance host adaptation to environmental perturbations.