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. 2009 Oct 6;106(40):17187-92.
doi: 10.1073/pnas.0904847106. Epub 2009 Sep 17.

Human gut microbiome adopts an alternative state following small bowel transplantation

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Human gut microbiome adopts an alternative state following small bowel transplantation

Amber L Hartman et al. Proc Natl Acad Sci U S A. .

Abstract

Small bowel transplants provide an exceptional opportunity for long-term study of the microbial ecology of the human small bowel VSports手机版. The ileostomy created at time of transplant for ongoing monitoring of the allograft provides access to samples of ileal effluent and mucosal biopsies. In this study, we used qPCR to assay the bacterial population of the small bowel lumen of 17 small bowel transplant patients over time. Surprisingly, the posttransplant microbial community was found to be dominated by Lactobacilli and Enterobacteria, both typically facultative anaerobes. This represents an inversion of the normal community that is dominated instead by the strictly anaerobic Bacteroides and Clostridia. We found this inverted community also in patients with ileostomies who did not receive a transplant, suggesting that the ileostomy itself is the primary ecological determinant shaping the microbiota. After surgical closure of the ileostomy, the community reverted to the normal structure. Therefore, we hypothesized that the ileostomy allows oxygen into the otherwise anaerobic distal ileum, thus driving the transition from one microbial community structure to another. Supporting this hypothesis, metabolomic profiling of both communities demonstrated an enrichment for metabolites associated with aerobic respiration in samples from patients with open ileostomies. Viewed from an ecological perspective, the two communities constitute alternative stable states of the human ileum. That the small bowel appears to function normally despite these dramatic shifts suggests that its ecological resilience is greater than previously realized. .

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Bacterial populations as measured by qPCR for each of the 17 SBT patients at all available time points. The bacterial group fractions (colored blocks) were calculated by summing the four individual groups and representing that total as 100%. The different x axis scales reflect each patient's individual timetable. x axis: red bar, graft rejection; green bar, postsurgical closure of the ileostomy; dashed black line beneath, day 0–125, the period used for time-binning (Figs. S2 and S3). Multipatient groupings: green box, ileostomy closed; red box, NOD2 mutations (SI Text); black box, died during the study; black arrow (patient 14), a second SBT at day 128.
Fig. 2.
Fig. 2.
Summary of the relative bacterial populations found under various clinical conditions. In each chart, the population of each of the four bacterial orders is shown as the geometric mean of its percentage of the total population. (A) Ileal effluent from transplant patients, ileostomy present. (B) Ileal effluent from nontransplant patients, ileostomy present (Fig. S4). (C) Biopsy samples from transplant patients, ileostomy present (Fig. 3). (D) Ileal effluent from transplant patients during transplant rejection, ileostomy present. (E) Ileal effluent from transplant patients, ileostomy closed. (F) Regraphed selected data from table 3 in ref. from biopsies of the terminal ileum of six healthy subjects.
Fig. 3.
Fig. 3.
Comparison of effluent and biopsy-associated populations. The log10 of the ratio between biopsy samples (positive direction) and effluent samples (negative direction) [i.e., log10(biopsy percentage/effluent percentage)] for all four subgroups of bacteria measured with qPCR. Biopsy and effluent samples taken during a period of graft rejection are colored in gray, whereas pathologically normal tissue is colored in black. The naming of samples is patient number first, followed by “d” (day pos-transplant of collection). Log scale on the x axis means that 2 is 100× greater proportion of that bacterial group relative to the other sample type.
Fig. 4.
Fig. 4.
Metabolomic network diagram of the 139 chemically identified metabolites. 62 metabolites (18.0%) showed significant enrichment in either preclosure or postclosure samples. Metabolites were mapped by structural similarity (see SI Text for details). Red, compounds enriched in preclosure samples; blue, compounds enriched in postclosure samples. Node size is proportional to the relative enrichment.
Fig. 5.
Fig. 5.
Model of alternative stable states of the small bowel ecosystem. In this ball-in-cup diagram (26), the horizontal length represents all possible states of the ecosystem, the vertical length represents increasing ecosystem instability. The two valleys represent two alternative stable states of the small bowel microbiota: either dominated by strict anaerobes or by facultative anaerobes. The pie charts illustrating the microbial commmunity compositions are from Fig. 2A, D, and E.

References

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