Paper reading (七十七)：Pretreatment gut microbiome predicts chemotherapy-related bloodstream infection

论文题目：Identification of an Intestinal Microbiota Signature Associated With Severity of Irritable Bowel Syndrome

scholar 引用：137

页数：21

发表时间：2016.10

发表刊物：Genome Medicine 

作者：Emmanuel Montassier, Gabriel A. Al-Ghalith, ..., Dan Knights 

摘要：

Background & Aims
We have limited knowledge about the association between the composition of the intestinal microbiota and clinical features of irritable bowel syndrome (IBS). We collected information on the fecal and mucosa-associated microbiota of patients with IBS and evaluated whether these were associated with symptoms.
Methods
We collected fecal and mucosal samples from adult patients who met the Rome III criteria for IBS at a secondary/tertiary care outpatient clinics in Sweden, as well as from healthy subjects. The exploratory set comprised 149 subjects (110 with IBS and 39 healthy subjects); 232 fecal samples and 59 mucosal biopsy samples were collected and analyzed by 16S ribosomal RNA targeted pyrosequencing. The validation set comprised 46 subjects (29 with IBS and 17 healthy subjects); 46 fecal samples, but no mucosal samples, were collected and analyzed. For each subject, we measured exhaled H2 and CH4, oro-anal transit time, and the severity of psychological and gastrointestinal symptoms. Fecal methanogens were measured by quantitative polymerase chain reaction. Numerical ecology analyses and a machine learning procedure were used to analyze the data.
Results
Fecal microbiota showed covariation with mucosal adherent microbiota. By using classic approaches, we found no differences in fecal microbiota abundance or composition between patients with IBS vs healthy patients. A machine learning procedure, a computational statistical technique, allowed us to reduce the 16S ribosomal RNA data complexity into a microbial signature for severe IBS, consisting of 90 bacterial operational taxonomic units. We confirmed the robustness of the intestinal microbial signature for severe IBS in the validation set. The signature was able to discriminate between patients with severe symptoms, patients with mild/moderate symptoms, and healthy subjects. By using this intestinal microbiota signature, we found IBS symptom severity to be associated negatively with microbial richness, exhaled CH4, presence of methanogens, and enterotypes enriched with Clostridiales or Prevotella species. This microbiota signature could not be explained by differences in diet or use of medications.
Conclusions
In analyzing fecal and mucosal microbiota from patients with IBS and healthy individuals, we identified an intestinal microbiota profile that is associated with the severity of IBS symptoms. Trial registration number: NCT01252550.

正文组织架构：

1. Introduction

2. Materials and Methods

2.1 Subject Recruitment and Study Design

2.2 Subject Characterization

2.3 Fecal and Mucosal Sample Collections and DNA Extraction

2.4 Microbial Composition Assessment

2.5 Detection of Methanobacteriales by Quantitative PCR

2.6 Numerical Ecology and Statistical Analysis

2.7 Access to Study Data

3. Results

3.1 Clinical Characteristics of IBS Patients and Healthy Subjects

3.2 Fecal and Mucosal Microbiota Are Structurally Distinct but Highly Correlated

3.3 Microbiota Diversity in Fecal and Biopsy Samples

3.4 Enterotype Stratification in Healthy Subjects and IBS Patients

3.5 Prevalence of Methanogens in Healthy Subjects and IBS Patients

3.6 Identification of a Microbial Signature for IBS Symptom Severity

3.7 Taxonomic Characterization of the Gut Microbial Signature for IBS Severity

3.8 Gut Microbial Signature for IBS Severity and Association With Clinical and Microbial Parameters

3.9 Gut Microbial Signature for IBS Severity and Association With Diet and Use of Medications

4. Discussion

正文部分内容摘录：

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

• identify a microbial signature

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

• We confirmed the robustness of the intestinal microbial signature for severe IBS in the validation set. 
• The signature was able to discriminate between patients with severe symptoms, patients with mild/moderate symptoms, and healthy subjects.
• By using this intestinal microbiota signature, we found IBS symptom severity to be associated negatively with microbial richness, exhaled CH4, presence of methanogens, and enterotypes enriched with Clostridiales or Prevotella species.
• This microbiota signature could not be explained by differences in diet or use of medications.
• In analyzing fecal and mucosal microbiota from patients with IBS and healthy individuals, we identified an intestinal microbiota profile that is associated with the severity of IBS symptoms. 
• In our study, the LASSO procedure identified 90 bacterial OTUs that could be used as a composite gut microbial signature for IBS severity. 

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

• The exploratory set comprised 149 subjects (110 with IBS and 39 healthy subjects); 232 fecal samples and 59 mucosal biopsy samples were collected
• The validation set comprised 46 subjects (29 with IBS and 17 healthy subjects); 46 fecal samples, but no mucosal samples, were collected 
• Numerical ecology analyses and a machine learning procedure were used to analyze the data.
• A machine learning procedure, a computational statistical technique, allowed us to reduce the 16S ribosomal RNA data complexity into a microbial signature for severe IBS, consisting of 90 bacterial operational taxonomic units.
• A machine learning procedure to identify a microbial signature for IBS severity was implemented using L1 regularized logistic regression31 (least absolute shrinkage and selection operator [LASSO]) using the LIBLINEAR library32 validated through a 10-fold independent cross-validation. Features selection and data transformation was processed as previously described.33 The performance of prediction models was assessed for its discriminative ability using the area under the receiver operating characteristic curve (AUROC) on exploratory and validation data sets. OTUs selected by machine learning were characterized further by their prevalence in healthy subjects and in patients with severe IBS (IBS-SSS > 300), and by their phylogenetic specificity (see Supplementary Material for more detail).

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

• Here, we used the LASSO logistic regression classifier9 implemented in LIBLINEAR,10 similar to Zeller et al,11 because it generates a parsimonious classification model that selects only a few features out of a potentially very large set.

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

• The performance of prediction models was assessed for its discriminative ability using the area under the receiver operating characteristic curve (AUROC) on exploratory and validation data sets.

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

• The use of machine learning has allowed us to circumvent the issues related to large microbial data sets and to better explore the microbial data. We were able to identify several interesting links between gut microbiota and the clinical profile.

7. Mine Question(Optional)