Human gut microbiome adopts an alternative state following small bowel transplantation

Amber L. Hartman, Denver M. Lough, Dinesh K. Barupal, Oliver Fiehn, Thomas Fishbein, Michael Zasloff, Jonathan A Eisen

Research output: Contribution to journalArticle

176 Citations (Scopus)

Abstract

Small bowel transplants provide an exceptional opportunity for long-term study of the microbial ecology of the human small bowel. 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.

Original languageEnglish (US)
Pages (from-to)17187-17192
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number40
DOIs
StatePublished - Oct 6 2009

Fingerprint

Ileostomy
Microbiota
Transplantation
Transplants
Ileum
Bacteroides
Metabolomics
Clostridium
Lactobacillus
Enterobacteriaceae
Ecology
Allografts
Gastrointestinal Microbiome
Respiration
Oxygen
Biopsy
Population

Keywords

  • 16S ribosomal RNA
  • Alternative stable state
  • Human microbiota
  • Intestinal allograft
  • Lactobacilli

ASJC Scopus subject areas

  • General

Cite this

Human gut microbiome adopts an alternative state following small bowel transplantation. / Hartman, Amber L.; Lough, Denver M.; Barupal, Dinesh K.; Fiehn, Oliver; Fishbein, Thomas; Zasloff, Michael; Eisen, Jonathan A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 40, 06.10.2009, p. 17187-17192.

Research output: Contribution to journalArticle

Hartman, Amber L. ; Lough, Denver M. ; Barupal, Dinesh K. ; Fiehn, Oliver ; Fishbein, Thomas ; Zasloff, Michael ; Eisen, Jonathan A. / Human gut microbiome adopts an alternative state following small bowel transplantation. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 40. pp. 17187-17192.
@article{e443efc21dde4cce9a824ed4db7c295e,
title = "Human gut microbiome adopts an alternative state following small bowel transplantation",
abstract = "Small bowel transplants provide an exceptional opportunity for long-term study of the microbial ecology of the human small bowel. 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.",
keywords = "16S ribosomal RNA, Alternative stable state, Human microbiota, Intestinal allograft, Lactobacilli",
author = "Hartman, {Amber L.} and Lough, {Denver M.} and Barupal, {Dinesh K.} and Oliver Fiehn and Thomas Fishbein and Michael Zasloff and Eisen, {Jonathan A}",
year = "2009",
month = "10",
day = "6",
doi = "10.1073/pnas.0904847106",
language = "English (US)",
volume = "106",
pages = "17187--17192",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "40",

}

TY - JOUR

T1 - Human gut microbiome adopts an alternative state following small bowel transplantation

AU - Hartman, Amber L.

AU - Lough, Denver M.

AU - Barupal, Dinesh K.

AU - Fiehn, Oliver

AU - Fishbein, Thomas

AU - Zasloff, Michael

AU - Eisen, Jonathan A

PY - 2009/10/6

Y1 - 2009/10/6

N2 - Small bowel transplants provide an exceptional opportunity for long-term study of the microbial ecology of the human small bowel. 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.

AB - Small bowel transplants provide an exceptional opportunity for long-term study of the microbial ecology of the human small bowel. 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.

KW - 16S ribosomal RNA

KW - Alternative stable state

KW - Human microbiota

KW - Intestinal allograft

KW - Lactobacilli

UR - http://www.scopus.com/inward/record.url?scp=70350125099&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70350125099&partnerID=8YFLogxK

U2 - 10.1073/pnas.0904847106

DO - 10.1073/pnas.0904847106

M3 - Article

C2 - 19805153

AN - SCOPUS:70350125099

VL - 106

SP - 17187

EP - 17192

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 40

ER -