Association Between Intestinal Microbiota Collected at Hospital Admission and Outcomes of Patients With Cirrhosis

Jasmohan S. Bajaj, Hugo E Vargas, K. Rajender Reddy, Jennifer C. Lai, Jacqueline G. O'Leary, Puneeta Tandon, Florence Wong, Robert Mitrani, Melanie B. White, Megan Kelly, Andrew Fagan, Rohan Patil, Shaimaa Sait, Masoumeh Sikaroodi, Leroy R. Thacker, Patrick M. Gillevet

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background & Aims: Inpatients with cirrhosis are prone to develop acute-on-chronic liver failure (ACLF). ACLF is associated with dysbiosis of the intestinal microbiota, which might serve as a prognostic factor. We investigated whether features of the intestinal microbiota associate organ failure, transfer to intensive care, and mortality within 30 days in patients admitted to the hospital with cirrhosis. Methods: Stool samples were collected from 181 patients with cirrhosis (age 56 years; mean model for end-stage liver disease score, 21; 43% with infections) at time of admission, from multiple hospitals in North America. Patients were followed for 30 days for development of ACLF, extra-hepatic organ failures, and death or hospice care. Microbiota were analyzed by 16s rRNA sequencing for alpha diversity (within groups), beta diversity (between groups), cirrhosis dysbiosis ratio (CDR), and taxa that differed between groups with vs without negative outcomes (individual organ failures, transfer to intensive care, ACLF, death, or hospice). Regression analyses were performed using microbial and clinical variables for each outcome. Results: ACLF developed in 8% of study subjects; 16% were transferred to intensive care and 21% died. Beta diversity of the intestinal microbiome was significantly different, whereas alpha diversity was similar, between subjects with vs without outcomes. The CDR was lower in subjects who developed ACLF, especially among those with renal failure. Taxa belonging to phylum Proteobacteria (Enterobacteriaceae, Campylobacteriaceae, and Pasteurellaceae) and Firmicutes (Enterococcaceae and Streptococcaceae) were associated with development of negative outcomes, whereas other Firmicutes members (Lachnospiraceae and Clostridiales) reduced risk of negative outcomes. Changes in the microbiota associated with extra-hepatic organ failure, transfer to intensive care, ACLF, and death, independently on logistic regression analyses. Conclusion: In hospitalized patients with cirrhosis, dysbiosis of the intestinal microbiota on admission (particularly changes in Protebacteria constituents) associates with increased risk of extra-hepatic organ failure, ACLF, and death, independent of clinical factors. Strategies to reduce gut dysbiosis might improve outcomes of patients with cirrhosis.

Original languageEnglish (US)
Pages (from-to)756-765.e3
JournalClinical Gastroenterology and Hepatology
Volume17
Issue number4
DOIs
StatePublished - Mar 1 2019

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Patient Admission
Dysbiosis
Fibrosis
Critical Care
Liver Failure
Microbiota
Streptococcaceae
Enterococcaceae
Pasteurellaceae
Regression Analysis
Hospice Care
Proteobacteria
End Stage Liver Disease
Hospices
Acute-On-Chronic Liver Failure
Gastrointestinal Microbiome
Enterobacteriaceae
North America
Renal Insufficiency
Inpatients

Keywords

  • Acute-on-chronic Liver Failure
  • Bacteria
  • Biomarker
  • Critical Care
  • Infection

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Association Between Intestinal Microbiota Collected at Hospital Admission and Outcomes of Patients With Cirrhosis. / Bajaj, Jasmohan S.; Vargas, Hugo E; Reddy, K. Rajender; Lai, Jennifer C.; O'Leary, Jacqueline G.; Tandon, Puneeta; Wong, Florence; Mitrani, Robert; White, Melanie B.; Kelly, Megan; Fagan, Andrew; Patil, Rohan; Sait, Shaimaa; Sikaroodi, Masoumeh; Thacker, Leroy R.; Gillevet, Patrick M.

In: Clinical Gastroenterology and Hepatology, Vol. 17, No. 4, 01.03.2019, p. 756-765.e3.

Research output: Contribution to journalArticle

Bajaj, JS, Vargas, HE, Reddy, KR, Lai, JC, O'Leary, JG, Tandon, P, Wong, F, Mitrani, R, White, MB, Kelly, M, Fagan, A, Patil, R, Sait, S, Sikaroodi, M, Thacker, LR & Gillevet, PM 2019, 'Association Between Intestinal Microbiota Collected at Hospital Admission and Outcomes of Patients With Cirrhosis', Clinical Gastroenterology and Hepatology, vol. 17, no. 4, pp. 756-765.e3. https://doi.org/10.1016/j.cgh.2018.07.022
Bajaj, Jasmohan S. ; Vargas, Hugo E ; Reddy, K. Rajender ; Lai, Jennifer C. ; O'Leary, Jacqueline G. ; Tandon, Puneeta ; Wong, Florence ; Mitrani, Robert ; White, Melanie B. ; Kelly, Megan ; Fagan, Andrew ; Patil, Rohan ; Sait, Shaimaa ; Sikaroodi, Masoumeh ; Thacker, Leroy R. ; Gillevet, Patrick M. / Association Between Intestinal Microbiota Collected at Hospital Admission and Outcomes of Patients With Cirrhosis. In: Clinical Gastroenterology and Hepatology. 2019 ; Vol. 17, No. 4. pp. 756-765.e3.
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abstract = "Background & Aims: Inpatients with cirrhosis are prone to develop acute-on-chronic liver failure (ACLF). ACLF is associated with dysbiosis of the intestinal microbiota, which might serve as a prognostic factor. We investigated whether features of the intestinal microbiota associate organ failure, transfer to intensive care, and mortality within 30 days in patients admitted to the hospital with cirrhosis. Methods: Stool samples were collected from 181 patients with cirrhosis (age 56 years; mean model for end-stage liver disease score, 21; 43{\%} with infections) at time of admission, from multiple hospitals in North America. Patients were followed for 30 days for development of ACLF, extra-hepatic organ failures, and death or hospice care. Microbiota were analyzed by 16s rRNA sequencing for alpha diversity (within groups), beta diversity (between groups), cirrhosis dysbiosis ratio (CDR), and taxa that differed between groups with vs without negative outcomes (individual organ failures, transfer to intensive care, ACLF, death, or hospice). Regression analyses were performed using microbial and clinical variables for each outcome. Results: ACLF developed in 8{\%} of study subjects; 16{\%} were transferred to intensive care and 21{\%} died. Beta diversity of the intestinal microbiome was significantly different, whereas alpha diversity was similar, between subjects with vs without outcomes. The CDR was lower in subjects who developed ACLF, especially among those with renal failure. Taxa belonging to phylum Proteobacteria (Enterobacteriaceae, Campylobacteriaceae, and Pasteurellaceae) and Firmicutes (Enterococcaceae and Streptococcaceae) were associated with development of negative outcomes, whereas other Firmicutes members (Lachnospiraceae and Clostridiales) reduced risk of negative outcomes. Changes in the microbiota associated with extra-hepatic organ failure, transfer to intensive care, ACLF, and death, independently on logistic regression analyses. Conclusion: In hospitalized patients with cirrhosis, dysbiosis of the intestinal microbiota on admission (particularly changes in Protebacteria constituents) associates with increased risk of extra-hepatic organ failure, ACLF, and death, independent of clinical factors. Strategies to reduce gut dysbiosis might improve outcomes of patients with cirrhosis.",
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T1 - Association Between Intestinal Microbiota Collected at Hospital Admission and Outcomes of Patients With Cirrhosis

AU - Bajaj, Jasmohan S.

AU - Vargas, Hugo E

AU - Reddy, K. Rajender

AU - Lai, Jennifer C.

AU - O'Leary, Jacqueline G.

AU - Tandon, Puneeta

AU - Wong, Florence

AU - Mitrani, Robert

AU - White, Melanie B.

AU - Kelly, Megan

AU - Fagan, Andrew

AU - Patil, Rohan

AU - Sait, Shaimaa

AU - Sikaroodi, Masoumeh

AU - Thacker, Leroy R.

AU - Gillevet, Patrick M.

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Background & Aims: Inpatients with cirrhosis are prone to develop acute-on-chronic liver failure (ACLF). ACLF is associated with dysbiosis of the intestinal microbiota, which might serve as a prognostic factor. We investigated whether features of the intestinal microbiota associate organ failure, transfer to intensive care, and mortality within 30 days in patients admitted to the hospital with cirrhosis. Methods: Stool samples were collected from 181 patients with cirrhosis (age 56 years; mean model for end-stage liver disease score, 21; 43% with infections) at time of admission, from multiple hospitals in North America. Patients were followed for 30 days for development of ACLF, extra-hepatic organ failures, and death or hospice care. Microbiota were analyzed by 16s rRNA sequencing for alpha diversity (within groups), beta diversity (between groups), cirrhosis dysbiosis ratio (CDR), and taxa that differed between groups with vs without negative outcomes (individual organ failures, transfer to intensive care, ACLF, death, or hospice). Regression analyses were performed using microbial and clinical variables for each outcome. Results: ACLF developed in 8% of study subjects; 16% were transferred to intensive care and 21% died. Beta diversity of the intestinal microbiome was significantly different, whereas alpha diversity was similar, between subjects with vs without outcomes. The CDR was lower in subjects who developed ACLF, especially among those with renal failure. Taxa belonging to phylum Proteobacteria (Enterobacteriaceae, Campylobacteriaceae, and Pasteurellaceae) and Firmicutes (Enterococcaceae and Streptococcaceae) were associated with development of negative outcomes, whereas other Firmicutes members (Lachnospiraceae and Clostridiales) reduced risk of negative outcomes. Changes in the microbiota associated with extra-hepatic organ failure, transfer to intensive care, ACLF, and death, independently on logistic regression analyses. Conclusion: In hospitalized patients with cirrhosis, dysbiosis of the intestinal microbiota on admission (particularly changes in Protebacteria constituents) associates with increased risk of extra-hepatic organ failure, ACLF, and death, independent of clinical factors. Strategies to reduce gut dysbiosis might improve outcomes of patients with cirrhosis.

AB - Background & Aims: Inpatients with cirrhosis are prone to develop acute-on-chronic liver failure (ACLF). ACLF is associated with dysbiosis of the intestinal microbiota, which might serve as a prognostic factor. We investigated whether features of the intestinal microbiota associate organ failure, transfer to intensive care, and mortality within 30 days in patients admitted to the hospital with cirrhosis. Methods: Stool samples were collected from 181 patients with cirrhosis (age 56 years; mean model for end-stage liver disease score, 21; 43% with infections) at time of admission, from multiple hospitals in North America. Patients were followed for 30 days for development of ACLF, extra-hepatic organ failures, and death or hospice care. Microbiota were analyzed by 16s rRNA sequencing for alpha diversity (within groups), beta diversity (between groups), cirrhosis dysbiosis ratio (CDR), and taxa that differed between groups with vs without negative outcomes (individual organ failures, transfer to intensive care, ACLF, death, or hospice). Regression analyses were performed using microbial and clinical variables for each outcome. Results: ACLF developed in 8% of study subjects; 16% were transferred to intensive care and 21% died. Beta diversity of the intestinal microbiome was significantly different, whereas alpha diversity was similar, between subjects with vs without outcomes. The CDR was lower in subjects who developed ACLF, especially among those with renal failure. Taxa belonging to phylum Proteobacteria (Enterobacteriaceae, Campylobacteriaceae, and Pasteurellaceae) and Firmicutes (Enterococcaceae and Streptococcaceae) were associated with development of negative outcomes, whereas other Firmicutes members (Lachnospiraceae and Clostridiales) reduced risk of negative outcomes. Changes in the microbiota associated with extra-hepatic organ failure, transfer to intensive care, ACLF, and death, independently on logistic regression analyses. Conclusion: In hospitalized patients with cirrhosis, dysbiosis of the intestinal microbiota on admission (particularly changes in Protebacteria constituents) associates with increased risk of extra-hepatic organ failure, ACLF, and death, independent of clinical factors. Strategies to reduce gut dysbiosis might improve outcomes of patients with cirrhosis.

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KW - Bacteria

KW - Biomarker

KW - Critical Care

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