Heterosis has been widely utilized in agricultural production. Despite over a century of extensive research, the underlying mechanisms of heterosis remain elusive. Most hypotheses and research have focused on the genetic basis of heterosis. However, the potential role of gut microbiota in heterosis has been largely ignored. Here, we carefully design a crossbreeding experiment with two distinct broiler breeds and conduct 16S rRNA amplicon and transcriptome sequencing to investigate the synergistic role of gut microbiota and host genes in driving heterosis. We find that the breast muscle weight of the hybrids exhibits a high heterosis, 6.28% higher than the mid-parent value. A notable difference is observed in the composition and potential function of cecal microbiota between hybrids and their parents. Over 90% of the differentially colonized microbiota and differentially expressed genes exhibit nonadditive patterns. Integrative analyses uncover associations between nonadditive genes and nonadditive microbiota, including a connection between the expression of cellular signaling pathways and metabolism-related genes and the abundance of Odoribacter, Oscillibacter, and Alistipes in hybrids. Moreover, higher abundances of these microbiota are related to better meat yield. In summary, these findings highlight the importance of gut microbiota in heterosis, serving as crucial factors that modulate heterosis expression in chickens.

Heterosis is widely used in agriculture. However, its molecular mechanisms are still unclear in plants. Here, we develop, sequence, and record the phenotypes of 418 hybrids from crosses between two testers and 265 rice varieties from a mini-core collection.
Phenotypic analysis shows that heterosis is dependent on genetic backgrounds and environments. By genome-wide association study of 418 hybrids and their parents, we find that nonadditive QTLs are the main genetic contributors to heterosis. We show that nonadditive QTLs are more sensitive to the genetic background and environment than additive ones. Further simulations and experimental analysis support a novel mechanism, homo-insufficiency under insufficient background (HoIIB), underlying heterosis. We propose heterosis in most cases is not due to heterozygote advantage but homozygote disadvantage under the insufficient genetic background.
The HoIIB model elucidates that genetic background insufficiency is the intrinsic mechanism of background dependence, and also the core mechanism of nonadditive effects and heterosis. This model can explain most known hypotheses and phenomena about heterosis, and thus provides a novel theory for hybrid rice breeding in future.