The microbiota and immune system non-genetically affect offspring phenotypes transgenerationally.

Area of Science:

• Microbiology
• Immunology
• Epigenetics
• Developmental Biology

Background:

• The host-microbiota relationship is crucial for mammalian immunity, metabolism, and development.
• Host phenotypes are known to change in response to microbial exposures.
• This study investigates if these phenotypic changes extend to subsequent generations.

Approach:

• Examined germ-free mice for sebum secretion defects and transcriptional changes across generations.
• Investigated T cell-deficient mice to explore the role of host-microbe interactions.
• Utilized in vitro fertilization with germ-free gametes to confirm epigenetic transmission.
• Analyzed small non-coding RNAs in gametes of germ-free and T cell-deficient mice.

Key Points:

• Germ-free mice exhibit persistent sebum secretion defects and transcriptional alterations across multiple generations.
• These transgenerational phenotypes are transmitted even after microbial colonization or breeding with conventional mice.
• Phenotypic transmission requires epigenetic information in gametes, as shown by in vitro fertilization experiments.
• Altered small non-coding RNAs in gametes of germ-free and T cell-deficient mice are linked to this inheritance.

Conclusions:

• A novel mechanism of transgenerational epigenetic inheritance, influenced by microbiota and the immune system, has been identified.
• This epigenetic inheritance facilitates rapid host adaptation to environmental changes by increasing phenotypic diversity.
• Small non-coding RNAs in gametes play a critical role in mediating these intergenerational effects.