BGI-Shenzhen, Shenzhen, 518083, China.
Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, DK-2100, Copenhagen, Denmark.
Microbiome. 2017 Apr 8;5(1):43. doi: 10.1186/s40168-017-0258-6.
It is well known that the microbiota of high-fat (HF) diet-induced obese mice differs from that of lean mice, but to what extent, this difference reflects the obese state or the diet is unclear. To dissociate changes in the gut microbiota associated with high HF feeding from those associated with obesity, we took advantage of the different susceptibility of C57BL/6JBomTac (BL6) and 129S6/SvEvTac (Sv129) mice to diet-induced obesity and of their different responses to inhibition of cyclooxygenase (COX) activity, where inhibition of COX activity in BL6 mice prevents HF diet-induced obesity, but in Sv129 mice accentuates obesity.
Using HiSeq-based whole genome sequencing, we identified taxonomic and functional differences in the gut microbiota of the two mouse strains fed regular low-fat or HF diets with or without supplementation with the COX-inhibitor, indomethacin. HF feeding rather than obesity development led to distinct changes in the gut microbiota. We observed a robust increase in alpha diversity, gene count, abundance of genera known to be butyrate producers, and abundance of genes involved in butyrate production in Sv129 mice compared to BL6 mice fed either a LF or a HF diet. Conversely, the abundance of genes involved in propionate metabolism, associated with increased energy harvest, was higher in BL6 mice than Sv129 mice.
The changes in the composition of the gut microbiota were predominantly driven by high-fat feeding rather than reflecting the obese state of the mice. Differences in the abundance of butyrate and propionate producing bacteria in the gut may at least in part contribute to the observed differences in obesity propensity in Sv129 and BL6 mice.
众所周知，高脂肪（HF）饮食诱导肥胖小鼠的微生物群与瘦小鼠的微生物群不同，但这种差异在多大程度上反映了肥胖状态或饮食尚不清楚。为了将与高脂肪喂养相关的肠道微生物群变化与与肥胖相关的变化区分开来，我们利用 C57BL/6JBomTac（BL6）和 129S6/SvEvTac（Sv129）小鼠对饮食诱导肥胖的不同易感性及其对环氧化酶（COX）活性抑制的不同反应，其中 BL6 小鼠中 COX 活性的抑制可防止 HF 饮食诱导的肥胖，但在 Sv129 小鼠中会加重肥胖。
使用基于 HiSeq 的全基因组测序，我们确定了两种小鼠品系（分别为常规低脂或高脂肪饮食，或补充 COX 抑制剂吲哚美辛）的肠道微生物群的分类和功能差异。高脂肪喂养而不是肥胖发展导致肠道微生物群发生明显变化。与 BL6 小鼠相比，无论是低脂饮食还是高脂肪饮食，Sv129 小鼠的 alpha 多样性、基因计数、已知丁酸产生菌的丰度以及参与丁酸产生的基因丰度均显著增加。相反，与增加能量收获相关的丙酸盐代谢相关基因的丰度在 BL6 小鼠中高于 Sv129 小鼠。
肠道微生物群组成的变化主要是由高脂肪喂养引起的，而不是反映小鼠的肥胖状态。肠道中丁酸和丙酸盐产生菌的丰度差异至少部分解释了 Sv129 和 BL6 小鼠肥胖倾向的差异。
