The Microbiota and T Cells Non-Genetically Modulate Inherited Phenotypes Transgenerationally
Cell reports(2024)
Univ Penn | Childrens Hosp Philadelphia
Abstract
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 celldeficient mice is strikingly and similarly altered. Our findings demonstrate that microbial- and immunedependent 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.
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Key words
microbiome,sebaceous glands,germ-free,skin,T cells,epigenetics,transgenerational inheritance,development
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