State Key Laboratory of Herbage Improvement and Grassland Agro-ecosystems; Key Laboratory of Grassland Livestock Industry Innovation, Ministry of Agriculture and Rural Afairs; Engineering Research Center of Grassland Industry, Ministry of Education; College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou, 730020, People's Republic of China.
College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, 730046, People's Republic of China.
NPJ Biofilms Microbiomes. 2024 Nov 17;10(1):129. doi: 10.1038/s41522-024-00606-5.
Rumen microbiotas are known to influence the fat deposition (FD) in sheep, but controversy over causality remains unresolved. Here, we performed microbiome-wide association studies (MWAS), microbiome genome-wide association analysis (mbGWAS) and bidirectional mendelian randomization (MR) analyses on 1,150 sheep with genotype data from whole-genome resequencing, 16S rRNA sequencing and multilevel FD-traits data. We quantified the proportion of individual variation in FD-traits explained by host genetics, rumen microbiota, and their interaction effects. We identified 32 rumen microbiota biomarkers including Bifidobacterium that were associated with FD-traits (P <0.05). Further, utilizing five MR methods, we identified eight causal associations between marker genera and FD-traits (P <0.05), including Butyrivibrio, Olsenella, p-2534-18B5 gut group, Prevotellaceae UCG-003, and Pseudobutyrivibrio causing forward causal effects on FD, and changes in Flexilinea and Suttonella induced by FD. To our knowledge, this is the inaugural attempt to employ MR in sheep to investigate the causal relationships between gastrointestinal microbiota and complex phenotypes, underscoring the potential for developing interventions related to adipose deposition in sheep from the perspective of the rumen microbiome.
瘤胃微生物群被认为会影响绵羊的脂肪沉积（FD），但因果关系仍存在争议。在这里，我们对 1150 只绵羊进行了宏基因组关联研究（MWAS）、宏基因组全基因组关联分析（mbGWAS）和双向孟德尔随机化（MR）分析，这些绵羊具有来自全基因组重测序、16S rRNA 测序和多层次 FD 性状数据的基因型数据。我们量化了 FD 性状中由宿主遗传学、瘤胃微生物群及其相互作用解释的个体变异比例。我们确定了 32 个与 FD 性状相关的瘤胃微生物群生物标志物，包括双歧杆菌（Bifidobacterium）（P<0.05）。此外，利用五种 MR 方法，我们确定了标记属与 FD 性状之间的八个因果关联（P<0.05），包括丁酸弧菌（Butyrivibrio）、奥氏杆菌属（Olsenella）、p-2534-18B5 肠道群、普雷沃氏菌科 UCG-003 和伪丁酸弧菌（Pseudobutyrivibrio）对 FD 产生正向因果效应，以及 FD 引起的 Flexilinea 和 Suttonella 的变化。据我们所知，这是首次利用 MR 研究绵羊来调查胃肠道微生物群与复杂表型之间的因果关系，这突显了从瘤胃微生物群角度开发与绵羊脂肪沉积相关干预措施的潜力。
