Paper reading (七十六)：Meta-Analysis Reveals Reproducible Gut Microbiome Alterations

论文题目：Meta-Analysis Reveals Reproducible Gut Microbiome Alterations in Response to a High-Fat Diet

scholar 引用：2

页数：13

发表时间：2019.08

发表刊物：Cell Host & Microbe

作者：Jordan E. Bisanz, Vaibhav Upadhyay,...Peter J. Turnbaugh

摘要：

Multiple research groups have shown that diet impacts the gut microbiome; however, variability in experimental design and quantitative assessment have made it challenging to assess the degree to which similar diets have reproducible effects across studies. Through an unbiased subject-level meta-analysis framework, we re-analyzed 27 dietary studies including 1,101 samples from rodents and humans. We demonstrate that a high-fat diet (HFD) reproducibly changes gut microbial community structure. Finer taxonomic analysis revealed that the most reproducible signals of a HFD are Lactococcus species, which we experimentally demonstrate to be common dietary contaminants. Additionally, a machine-learning approach defined a signature that predicts the dietary intake of mice and demonstrated that phylogenetic and gene-centric transformations of this model can be translated to humans. Together, these results demonstrate the utility of microbiome meta-analyses in identifying robust and reproducible features for mechanistic studies in preclinical models.

Highlights：

• A generalizable approach is presented for meta-analysis of microbiome datasets
• High-fat diets induce reproducible shifts in the mouse gut microbiome
• Nonviable Lactococcus(乳球菌) contamination is widespread in experimental diets
• Phylogenetic and gene signatures translate to human microbiomes

正文组织架构：

1. Introduction

2. Results

2.1 Study Selection and Characteristics

2.2 Effect of HFD on Microbial Diversity

2.3 HFD Reproducibly Alters Community Composition

2.4 Predictive Microbial Responses to HFD

3.  Discussion

正文部分内容摘录：

1. Biological Problem: What biological problems have been solved in this paper?

• meta-analysis
•  investigating the effect of HFD on the gut microbiome in murine models.

2. Main discoveries: What is the main discoveries in this paper?

• Through an unbiased subject-level meta-analysis framework, we re-analyzed 27 dietary studies including 1,101 samples from rodents and humans. 明明说筛出来了25个研究做荟萃分析，但是为什么这里就变成了27个呢。。。 Two additional human studies were identified to examine translatability of mouse studies to humans 原来如此
• We demonstrate that a high-fat diet (HFD) reproducibly changes gut microbial community structure.
• Finer taxonomic analysis revealed that the most reproducible signals of a HFD are Lactococcus species, which we experimentally demonstrate to be common dietary contaminants.
• a machine-learning approach defined a signature that predicts the dietary intake of mice and demonstrated that phylogenetic and gene-centric transformations of this model can be translated to humans.
• Despite major differences in experimental design, we are able to identify microbial signatures that are consistent and predictive of HFD intake. 

3. ML(Machine Learning) Methods: What are the ML methods applied in this paper?

• A total of 427 unique studies were retrieved by our search methodology, this left 25 murine studies for inclusion in our meta-analysis.  从427个研究中筛选25个合格的。。。这工作量，好吧。服。。。
• We used a random forest classifier to define reliable biomarkers of the gut microbial response to HFD. As a first pass, we conducted a leave-one-dataset-out analysis in which each study using conventionally colonized mice was systematically excluded from training and then subsequently predicted using the model, demonstrating excellent reproducibility with a median area under the receiver curve (AUROC) of 0.93 (interquartile range = 0.22) using OTU abundances.

4. ML Advantages: Why are these ML methods better than the traditional methods in these biological problems?

5. Biological Significance: What is the biological significance of these ML methods’ results?

6. Prospect: What are the potential applications of these machine learning methods in biological science?

• these results demonstrate the utility of microbiome meta-analyses in identifying robust and reproducible features for mechanistic studies in preclinical models.
• The statistical power of our meta-analysis is also reduced by the large extent of missing data for published studies. 

7. Mine Question(Optional)