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. 2013 Oct 1:14:669.
doi: 10.1186/1471-2164-14-669.

Gut microbiota dysbiosis and bacterial community assembly associated with cholesterol gallstones in large-scale study

Tao Wu  1 , Zhigang Zhang, Bin Liu, Dezhi Hou, Yun Liang, Jie Zhang, Peng Shi
Affiliations

Gut microbiota dysbiosis and bacterial community assembly associated with cholesterol gallstones in large-scale study

Tao Wu et al. BMC Genomics. .

Abstract

Background: Elucidating gut microbiota among gallstone patients as well as the complex bacterial colonization of cholesterol gallstones may help in both the prediction and subsequent lowered risk of cholelithiasis. To this end, we studied the composition of bacterial communities of gut, bile, and gallstones from 29 gallstone patients as well as the gut of 38 normal individuals, examining and analyzing some 299, 217 bacterial 16S rRNA gene sequences from 120 samples.

Results: First, as compared with normal individuals, in gallstone patients there were significant (P < 0.001) increases of gut bacterial phylum Proteobacteria and decreases of three gut bacterial genera, Faecalibacterium, Lachnospira, and Roseburia. Second, about 70% of gut bacterial operational taxonomic units (OTUs) from gallstone patients were detectable in the biliary tract and bacteria diversity of biliary tract was significantly (P < 0.001) higher than that of gut. Third, analysis of the biliary tract core microbiome (represented by 106 bacteria OTUs) among gallstone patients showed that 33.96% (36/106) of constituents can be matched to known bacterial species (15 of which have publicly available genomes). A genome-wide search of MDR, BSH, bG, and phL genes purpotedly associated with the formation of cholesterol gallstones showed that all 15 species with known genomes (e.g., Propionibacterium acnes, Bacteroides vulgates, and Pseudomonas putida) contained at least contained one of the four genes. This finding could potentially provide underlying information needed to explain the association between biliary tract microbiota and the formation of cholesterol gallstones.

Conclusions: To the best of our knowledge, this is the first study to discover gut microbiota dysbiosis among gallstone patients, the presence of which may be a key contributor to the complex bacteria community assembly linked with the presence of cholesterol gallstones. Likewise, this study also provides the first large-scale glimpse of biliary tract microbiota potentially associated with cholesterol gallstones. Such a characterization of the biliary tract core microbiome has potentially important biological and medical implications regarding the role of bacteria in the formation cholesterol gallstones.

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Figures

Figure 1
Figure 1
Phyla level comparisons of microbial components between the gut and biliary tract. Only top nine phyla shown. ***P < 0.001.
Figure 2
Figure 2
Genera level comparisons of microbial components between gut and biliary tract. In total, 38 genera distributions are shown, including those genera of each type of sample with relative abundance of at least 0.01%, respectively. Taxons marked by stars were unclassified. C., Clostridiaceae family. L., Lachnospiraceae family. R., Ruminococcaceae family. *P < 0.05.
Figure 3
Figure 3
Microbiota analysis of separates samples based upon where they live in the community. Hierarchical average clustering based on the Spearman/Pearson correlation coefficients of the proportion of all taxons, filtered for taxonomic variables with over 50% percent zeroes. Non-informative variables are characterized using the coefficient of variation (mean/standard deviation). Data normalization between samples was conducted by Sum, and those between taxons Pareto Scaling (mean-centered and divided by the square root of standard deviation of each variable). In total, 35 taxonomic features are shown in the heatmap, with statistical significance among four types of samples based on T-test/ANOVA analyses.
Figure 4
Figure 4
Quantitative comparisons of bacterial OTUs between the gut and biliary tract. Numbers in brackets denote OTU number discovered from each of four different types of samples, corresponding to four different colored boxes. Number in brackets located at the colored boxes denotes shared OTUs (at overlapped boxes) across either the four types of samples or those unique to a given sample type.
Figure 5
Figure 5
Pipeline for identifying biliary tract core microbiome and potential microbial species associated with the presence of gallstones.
See this image and copyright information in PMC

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