Quantitatively Different, yet Qualitatively Alike: A Meta-Analysis of the Mouse Core Gut Microbiome with a View towards the Human Gut Microbiome

Background
A number of human diseases such as obesity and diabetes are associated with changes or imbalances in the gut microbiota (GM). Laboratory mice are commonly used as experimental models for such disorders. The introduction and dynamic development of next generation sequencing techniques have enabled detailed mapping of the GM of both humans and animal models. Nevertheless there is still a significant knowledge gap regarding the human and mouse common GM core and thus the applicability of the latter as an animal model. The aim of the present study was to identify inter- and intra-individual differences and similarities between the GM composition of particular mouse strains and humans.
Methodology/Principal Findings
A total of 1509428 high quality tag-encoded partial 16S rRNA gene sequences determined using 454/FLX Titanium (Roche) pyro-sequencing reflecting the GM composition of 32 human samples from 16 individuals and 88 mouse samples from three laboratory mouse strains commonly used in diabetes research were analyzed using Principal Coordinate Analysis (PCoA), nonparametric multivariate analysis of similarity (ANOSIM) and alpha diversity measures. A reliable cutoff threshold for low abundant taxa estimated on the basis of the present study is recommended for similar trials.
Conclusions/Significance
Distinctive quantitative differences in the relative abundance of most taxonomic groups between the examined categories were found. All investigated mouse strains clustered separately, but with a range of shared features when compared to the human GM. However, both mouse fecal, caecal and human fecal samples shared to a large extent not only representatives of the same phyla, but also a substantial fraction of common genera, where the number of shared genera increased with sequencing depth. In conclusion, the GM of mice and humans is quantitatively different (in terms of abundance of specific phyla and species) but share a large qualitatively similar core.

背景
诸多人类疾病（如肥胖症与糖尿病）均与肠道菌群（gut microbiota, GM）的改变或失衡密切相关。实验小鼠常被用作这类疾病研究的动物模型。随着下一代测序技术的问世与不断发展，研究者得以对人类与动物模型的肠道菌群进行精细解析。然而，目前在人与小鼠共有的肠道菌群核心特征，以及后者作为动物模型的适用性方面，仍存在显著的认知空白。本研究旨在明确特定品系实验小鼠与人类的肠道菌群组成在个体间及个体内的差异与相似性。

研究方法/主要结果
本研究共纳入经罗氏454/FLX Titanium焦磷酸测序获得的1509428条高质量标签编码的部分16S rRNA基因序列，这些序列反映了16名个体的32份人类样本以及3种常用于糖尿病研究的实验小鼠品系的88份样本的肠道菌群组成；随后采用主坐标分析（Principal Coordinate Analysis, PCoA）、非参数多元相似性分析（Analysis of Similarity, ANOSIM）以及α多样性指数对上述数据进行分析。本研究还基于实验数据估算得到了低丰度分类群的可靠截断阈值，可为同类研究提供参考。

结论与意义
本研究发现，所分析的各组样本间绝大多数分类群的相对丰度存在显著的定量差异。所有被研究的小鼠品系菌群均各自聚类，但与人类肠道菌群相比仍存在若干共有特征。不过，小鼠粪便、盲肠样本与人类粪便样本不仅在菌门水平上存在大量共有类群，在菌属水平上也有相当比例的共有菌属，且共有菌属的数量随测序深度增加而增多。综上，小鼠与人类的肠道菌群在定量层面存在差异（具体表现为特定菌门与菌种的丰度不同），但二者拥有大量在定性层面高度相似的核心菌群。