The effect of the cecal microbiome on growth of rabbits that were fed under different regimes has been studied previously. However, the term “effect” carries a causal meaning that can be confounded because of potential genetic associations between the microbiome and production traits. Structural equation models (SEM) can help disentangle such a complex interplay by decomposing the effect on a production trait into direct host genetics effects and indirect host genetic effects that are exerted through microbiota effects. These indirect effects can be estimated via structural coefficients that measure the effect of the microbiota on growth while the effects of the host genetics are kept constant. In this study, we applied the SEM approach to infer causal relationships between the cecal microbiota and growth of rabbits fed under ad libitum (ADGAL) or restricted feeding (ADGR). We identified structural coefficients that are statistically different from 0 for 138 of the 946 operational taxonomic units (OTU) analyzed. However, only 15 and 38 of these 138 OTU had an effect greater than 0.2 phenotypic standard deviations (SD) on ADGAL and ADGR, respectively. Many of these OTU had a negative effect on both traits. The largest effects on ADGR were exerted by an OTU that is taxonomically assigned to the Desulfovibrio genus (− 1.929 g/d, CSS-normalized OTU units) and by an OTU that belongs to the Ruminococcaceae family (1.859 g/d, CSS-normalized OTU units). For ADGAL, the largest effect was from OTU that belong to the S24-7 family (− 1.907 g/d, CSS-normalized OTU units). In general, OTU that had a substantial effect had low to moderate estimates of heritability. Disentangling how direct and indirect effects act on production traits is relevant to fully describe the processes of mediation but also to understand how these traits change before considering the application of an external intervention aimed at changing a given microbial composition by blocking/promoting the presence of a particular microorganism.

中文翻译：

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通过结构方程模型解开兔子生长与盲肠微生物群之间的因果关系

先前已经研究了盲肠微生物组对在不同喂养条件下喂养的兔子生长的影响。然而，术语“影响”具有因果关系，由于微生物组和生产性状之间潜在的遗传关联，可能会混淆。结构方程模型 (SEM) 可以通过将对生产性状的影响分解为直接宿主遗传效应和通过微生物群效应施加的间接宿主遗传效应来帮助理清这种复杂的相互作用。这些间接影响可以通过结构系数来估计，结构系数衡量微生物群对生长的影响，同时宿主遗传学的影响保持不变。在这项研究中，我们应用 SEM 方法来推断盲肠微生物群与随意喂养 (ADGAL) 或限制喂养 (ADGR) 的兔子生长之间的因果关系。我们确定了分析的 946 个操作分类单元 (OTU) 中的 138 个的结构系数在统计上不同于 0。然而，这 138 个 OTU 中只有 15 个和 38 个分别对 ADGAL 和 ADGR 具有大于 0.2 表型标准差 (SD) 的影响。其中许多 OTU 对这两种性状都有负面影响。对 ADGR 影响最大的是在分类学上属于脱硫弧菌属的 OTU（− 1.929 g/d，CSS 归一化 OTU 单位）和属于瘤胃球菌科的 OTU（1.859 g/d，CSS 归一化） OTU单位）。对于 ADGAL，最大的影响来自属于 S24-7 家族的 OTU（− 1.907 g/d，CSS 归一化 OTU 单位）。一般而言，具有实质性影响的 OTU 对遗传力的估计值低至中等。弄清直接和间接影响如何影响生产性状与充分描述调解过程有关，而且在考虑应用旨在通过阻断/促进特定的微生物。