A large number of studies have highlighted the importance of gut microbiome composition in shaping fat deposition in mammals. Several studies have also highlighted how host genome controls the abundance of certain species that make up the gut microbiota. We propose a systematic approach to infer how the host genome can control the gut microbiome, which in turn contributes to the host phenotype determination. We implemented a mediation test that can be applied to measured and latent dependent variables to describe fat deposition in swine (Sus scrofa). In this study, we identify several host genomic features having a microbiome-mediated effects on fat deposition. This demonstrates how the host genome can affect the phenotypic trait by inducing a change in gut microbiome composition that leads to a change in the phenotype. Host genomic variants identified through our analysis are different than the ones detected in a traditional genome-wide association study. In addition, the use of latent dependent variables allows for the discovery of additional host genomic features that do not show a significant effect on the measured variables. Microbiome-mediated host genomic effects can help understand the genetic determination of fat deposition. Since their contribution to the overall genetic variance is usually not included in association studies, they can contribute to filling the missing heritability gap and provide further insights into the host genome – gut microbiome interplay. Further studies should focus on the portability of these effects to other populations as well as their preservation when pro-/pre-/anti-biotics are used (i.e. remediation).

大量研究强调了肠道微生物组组成对哺乳动物脂肪沉积形成的重要性。一些研究还强调了宿​​主基因组如何控制组成肠道微生物群的某些物种的丰度。我们提出了一种系统的方法来推断宿主基因组如何控制肠道微生物组，进而有助于宿主表型的确定。我们实施了一项调解测试，该测试可用于测量和潜在因变量来描述猪中的脂肪沉积（Sus scrofa）。在这项研究中，我们确定了几个宿主基因组特征对脂肪沉积具有微生物组介导的作用。这证明了宿主基因组如何通过诱导肠道微生物组组成的变化而导致表型发生变化，从而影响表型性状。通过我们的分析鉴定出的宿主基因组变异与传统的全基因组关联研究中检测到的变异不同。另外，潜在因变量的使用允许发现其他宿主基因组特征，这些特征对测量变量没有显着影响。微生物组介导的宿主基因组效应可以帮助了解脂肪沉积的遗传测定。由于关联研究通常不包括它们对整体遗传变异的贡献，它们可以帮助填补缺失的遗传力鸿沟，并为宿主基因组（肠道微生物组之间的相互作用）提供进一步的见解。进一步的研究应侧重于这些效应对其他人群的可移植性以及使用前/前/后抗生素（即补救措施）时的保存效果。