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. 2014 May 12;9(5):e97048.
doi: 10.1371/journal.pone.0097048. eCollection 2014.

Aerosol Mycobacterium tuberculosis infection causes rapid loss of diversity in gut microbiota

Kathryn Winglee  1 , Emiley Eloe-Fadrosh  2 , Shashank Gupta  3 , Haidan Guo  1 , Claire Fraser  2 , William Bishai  3
Affiliations

Aerosol Mycobacterium tuberculosis infection causes rapid loss of diversity in gut microbiota

Kathryn Winglee et al. PLoS One. .

Abstract

Mycobacterium tuberculosis is an important human pathogen, and yet diagnosis remains challenging. Little research has focused on the impact of M. tuberculosis on the gut microbiota, despite the significant immunological and homeostatic functions of the gastrointestinal tract. To determine the effect of M. tuberculosis infection on the gut microbiota, we followed mice from M. tuberculosis aerosol infection until death, using 16S rRNA sequencing. We saw a rapid change in the gut microbiota in response to infection, with all mice showing a loss and then recovery of microbial community diversity, and found that pre-infection samples clustered separately from post-infection samples, using ecological beta-diversity measures. The effect on the fecal microbiota was observed as rapidly as six days following lung infection. Analysis of additional mice infected by a different M. tuberculosis strain corroborated these results, together demonstrating that the mouse gut microbiota significantly changes with M. tuberculosis infection.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Community structure of individual M. tuberculosis CDC1551 infected mice over time.
(A) Survival time in days post-infection for each mouse. (B) Phylogenetic profile of bacterial genera. Stacked bar charts in chronological order for each mouse of the 18 main genera identified based on ≥1% abundance present in at least two samples. Unclassified sequences are not shown. Black colored bars along x-axis indicate samples taken prior to infection, while red colored bars indicate post-infection. Each group represents an individual mouse, followed to death. The mice are represented sequentially, with mouse 1 on the left, and mouse 5 on the right. (C) Community diversity in each sample as measured by the Shannon diversity index, plotted against the percent survival time.
Figure 2
Figure 2. Composition of the gut microbiota significantly changes with M. tuberculosis CDC1551 infection.
(A) Unweighted and (B) weighted Unifrac measures of beta-diversity visualized using Principle Coordinate Analysis (PCoA) following individual mice over time with M. tuberculosis CDC1551 infection. Blue dots indicate samples collected pre-infection. Red dots indicate samples collected post-infection. Variance for first two component axes is shown as percent of total variance. An analysis of molecular variance (AMOVA) was performed to test whether the separation of uninfected and TB-infected samples was statistically significant. In both unweighted and weighted Unifrac measures, there was a statistically significant difference (p<0.001). (C) Network analysis of OTUs partitioned among samples, using a five sequence cutoff, and colored by phylum.
Figure 3
Figure 3. Differentially abundant OTUs identified between pre-infection and post-infection.
OTUs are ordered by consensus taxonomic classification, with OTUs scaled by relative abundances for each row ranging from low relative abundance (blue) to high relative abundance (red).
Figure 4
Figure 4. Phylogenetic profile of bacterial genera for uninfected and M. tuberculosis H37Rv infected mice.
Stacked bar charts for uninfected and H37Rv-infected mice of the 16 main genera identified based on ≥1% abundance present in at least two samples. Unclassified sequences are not shown. The black colored bar along x-axis indicates the five uninfected mice, while the red colored bar indicates mice infected with H37Rv.
Figure 5
Figure 5. Gut microbiota composition of M. tuberculosis H37Rv infected mice is significantly different from uninfected mice.
(A) Unweighted and (B) weighted Unifrac measures of beta-diversity visualized using Principle Coordinate Analysis (PCoA) for the comparison of H37Rv-infected mice to uninfected mice at a single time point. Blue dots indicate samples collected pre-infection. Red dots indicate samples collected post-infection. Variance for first two component axes is shown as percent of total variance. In both unweighted and weighted Unifrac measures, there was a statistically significant difference (AMOVA p≤0.005). (C) Network analysis of OTUs partitioned among samples, using a five sequence cutoff, and colored by phylum.
Figure 6
Figure 6. Differentially abundant OTUs identified between uninfected and M. tuberculosis H37Rv infected mice.
OTUs are ordered by consensus taxonomic classification, with OTUs scaled by relative abundances for each row ranging from low relative abundance (blue) to high relative abundance (red).
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