Mounting evidence demonstrates that paternal diet programs offspring metabolism. However, the contribution of a pre-conception paternal high protein (HP) diet to offspring metabolism, gut microbiota, and epigenetic changes remains unclear. Here we show that paternal HP intake in Sprague Dawley rats programs protective metabolic outcomes in offspring. Compared to paternal high fat/sucrose (HF/S), HP diet improved body composition and insulin sensitivity and improved circulating satiety hormones and cecal short-chain fatty acids compared to HF/S and control diet (P < .05). Further, using 16S rRNA gene sequencing to assess gut microbial composition, we observed increased alpha diversity, distinct bacterial clustering, and increased abundance of Bifidobacterium, Akkermansia, Bacteroides, and Marvinbryantia in HP fathers and/or male and female adult offspring. At the epigenetic level, DNMT1and 3b expression was altered intergenerationally. Our study identifies paternal HP diet as a modulator of gut microbial composition, epigenetic markers, and metabolic function intergenerationally.

中文翻译：

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父系高蛋白饮食可代际调节大鼠的身体成分、胰岛素敏感性、表观遗传学和肠道微生物群

越来越多的证据表明，父亲的饮食会影响后代的新陈代谢。然而，受孕前父亲高蛋白（HP）饮食对后代代谢、肠道微生物群和表观遗传变化的贡献仍不清楚。在这里，我们表明在 Sprague Dawley 大鼠中父本 HP 摄入对后代的保护性代谢结果进行了编程。与父亲的高脂肪/蔗糖 (HF/S) 相比，HP 饮食与 HF/S 和对照饮食相比，改善了身体成分和胰岛素敏感性，并改善了循环饱腹感激素和盲肠短链脂肪酸 ( P  < .05)。此外，使用 16S rRNA 基因测序来评估肠道微生物组成，我们观察到增加的 alpha 多样性、不同的细菌聚类和增加的双歧杆菌、阿克曼氏菌、拟杆菌、HP 父亲和/或雄性和雌性成年后代中的Marvinbryantia和Marvinbryantia。在表观遗传水平上，DNMT1和3b的表达发生代际改变。我们的研究将父系 HP 饮食确定为代际肠道微生物组成、表观遗传标记和代谢功能的调节剂。