title: Delayed development induced by toxicity to the host can be inherited by a bacterial-dependent, transgenerational effect.
abstract: Commensal gut bacteria in many species including flies are integral part of their host, and are known to influence its development and homeostasis within generation. Here we report an unexpected impact of host-microbe interactions, which mediates multi-generational, non-Mendelian inheritance of a stress-induced phenotype. We have previously shown that exposure of fly larvae to G418 antibiotic induces transgenerationally heritable phenotypes, including a delay in larval development, gene induction in the gut and morphological changes. We now show that G418 selectively depletes commensal Acetobacter species and that this depletion explains the heritable delay, but not the inheritance of the other phenotypes. Notably, the inheritance of the delay was mediated by a surprising trans-generational effect. Specifically, bacterial removal from F1 embryos did not induce significant delay in F1 larvae, but nonetheless led to a considerable delay in F2. This effect maintains a delay induced by bacterial-independent G418 toxicity to the host. In line with these findings, reintroduction of isolated Acetobacter species prevented the inheritance of the delay. We further show that this prevention is partly mediated by vitamin B2 (Riboflavin) produced by these bacteria; exogenous Riboflavin led to partial prevention and inhibition of Riboflavin synthesis compromised the ability of the bacteria to prevent the inheritance. These results identify host-microbe interactions as a hitherto unrecognized factor capable of mediating non-Mendelian inheritance of a stress-induced phenotype.
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science Rehovot, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Fridmann-Sirkis
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science Rehovot, Israel.
authors.forename: Shay
authors.initials: S
authors.lastname: Stern
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science Rehovot, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Elgart
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science Rehovot, Israel.
authors.forename: Matana
authors.initials: M
authors.lastname: Galili
authors.affiliation: Department of Physics of Complex Systems, Weizmann Institute of Science Rehovot, Israel.
authors.forename: Amit
authors.initials: A
authors.lastname: Zeisel
authors.affiliation: Department of Computer Science, The Open University Raanana, Israel.
authors.forename: Noam
authors.initials: N
authors.lastname: Shental
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science Rehovot, Israel.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Soen
keywords: D. melanogaster; epigenetics; host–microbe interactions; non-Mendelian inheritance; stress responses