Recurrent Clostridium difficile infection associates with distinct bile acid and microbiome profiles
Background: The healthy microbiome protects against the development of Clostridium difficile infection (CDI), which typically develops following antibiotics. The microbiome metabolises primary to secondary bile acids, a process if disrupted by antibiotics, may be critical for the initiation of CDI....
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Wiley Blackwell
2017
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| Online Access: | http://hdl.handle.net/1721.1/109870 https://orcid.org/0000-0002-8033-8380 https://orcid.org/0000-0001-8294-9364 |
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| author | Allegretti, J. R. Li, N. Bogart, E. Bullock, K. Gerber, G. K. Bry, L. Clish, C. B. Korzenik, J. R. Kearney, Sean M Alm, Eric J |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Allegretti, J. R. Li, N. Bogart, E. Bullock, K. Gerber, G. K. Bry, L. Clish, C. B. Korzenik, J. R. Kearney, Sean M Alm, Eric J |
| author_sort | Allegretti, J. R. |
| collection | MIT |
| description | Background: The healthy microbiome protects against the development of Clostridium difficile infection (CDI), which typically develops following antibiotics. The microbiome metabolises primary to secondary bile acids, a process if disrupted by antibiotics, may be critical for the initiation of CDI.
Aim: To assess the levels of primary and secondary bile acids associated with CDI and associated microbial changes.
Methods: Stool and serum were collected from patients with (i) first CDI (fCDI), (ii) recurrent CDI (rCDI) and (iii) healthy controls. 16S rRNA sequencing and bile salt metabolomics were performed. Random forest regression models were constructed to predict disease status. PICRUSt analyses were used to test for associations between predicted bacterial bile salt hydrolase (BSH) gene abundances and bile acid levels.
Results: Sixty patients (20 fCDI, 19 rCDI and 21 controls) were enrolled. Secondary bile acids in stool were significantly elevated in controls compared to rCDI and fCDI (P < 0.0001 and P = 0.0007 respectively). Primary bile acids in stool were significantly elevated in rCDI compared to controls (P < 0.0001) and in rCDI compared to fCDI (P = 0.02). Using random forest regression, we distinguished rCDI and fCDI patients 84.2% of the time using bile acid ratios. Stool deoxycholate to glycoursodeoxycholate ratio was the single best predictor. PICRUSt analyses found significant differences in predicted abundances of bacterial BSH genes in stool samples across the groups.
Conclusions: Primary and secondary bile acid composition in stool was different in those with rCDI, fCDI and controls. The ratio of stool deoxycholate to glycoursodeoxycholate was the single best predictor of disease state and may be a potential biomarker for recurrence. |
| first_indexed | 2024-09-23T08:44:12Z |
| format | Article |
| id | mit-1721.1/109870 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:44:12Z |
| publishDate | 2017 |
| publisher | Wiley Blackwell |
| record_format | dspace |
| spelling | mit-1721.1/1098702022-09-30T10:52:22Z Recurrent Clostridium difficile infection associates with distinct bile acid and microbiome profiles Allegretti, J. R. Li, N. Bogart, E. Bullock, K. Gerber, G. K. Bry, L. Clish, C. B. Korzenik, J. R. Kearney, Sean M Alm, Eric J Massachusetts Institute of Technology. Department of Biological Engineering Kearney, Sean M Alm, Eric J Background: The healthy microbiome protects against the development of Clostridium difficile infection (CDI), which typically develops following antibiotics. The microbiome metabolises primary to secondary bile acids, a process if disrupted by antibiotics, may be critical for the initiation of CDI. Aim: To assess the levels of primary and secondary bile acids associated with CDI and associated microbial changes. Methods: Stool and serum were collected from patients with (i) first CDI (fCDI), (ii) recurrent CDI (rCDI) and (iii) healthy controls. 16S rRNA sequencing and bile salt metabolomics were performed. Random forest regression models were constructed to predict disease status. PICRUSt analyses were used to test for associations between predicted bacterial bile salt hydrolase (BSH) gene abundances and bile acid levels. Results: Sixty patients (20 fCDI, 19 rCDI and 21 controls) were enrolled. Secondary bile acids in stool were significantly elevated in controls compared to rCDI and fCDI (P < 0.0001 and P = 0.0007 respectively). Primary bile acids in stool were significantly elevated in rCDI compared to controls (P < 0.0001) and in rCDI compared to fCDI (P = 0.02). Using random forest regression, we distinguished rCDI and fCDI patients 84.2% of the time using bile acid ratios. Stool deoxycholate to glycoursodeoxycholate ratio was the single best predictor. PICRUSt analyses found significant differences in predicted abundances of bacterial BSH genes in stool samples across the groups. Conclusions: Primary and secondary bile acid composition in stool was different in those with rCDI, fCDI and controls. The ratio of stool deoxycholate to glycoursodeoxycholate was the single best predictor of disease state and may be a potential biomarker for recurrence. American College of Gastroenterology (Clinical Research Award ACGJR-017-2015) 2017-06-14T20:05:30Z 2017-06-14T20:05:30Z 2016-04 2016-03 Article http://purl.org/eprint/type/JournalArticle 1365-2036 0269-2813 http://hdl.handle.net/1721.1/109870 Allegretti, J. R. et al. “Recurrent Clostridium Difficile Infection Associates with Distinct Bile Acid and Microbiome Profiles.” Alimentary Pharmacology & Therapeutics 43.11 (2016): 1142–1153. https://orcid.org/0000-0002-8033-8380 https://orcid.org/0000-0001-8294-9364 en_US http://dx.doi.org/10.1111/apt.13616 Alimentary Pharmacology & Therapeutics Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Wiley Blackwell PMC |
| spellingShingle | Allegretti, J. R. Li, N. Bogart, E. Bullock, K. Gerber, G. K. Bry, L. Clish, C. B. Korzenik, J. R. Kearney, Sean M Alm, Eric J Recurrent Clostridium difficile infection associates with distinct bile acid and microbiome profiles |
| title | Recurrent Clostridium difficile infection associates with distinct bile acid and microbiome profiles |
| title_full | Recurrent Clostridium difficile infection associates with distinct bile acid and microbiome profiles |
| title_fullStr | Recurrent Clostridium difficile infection associates with distinct bile acid and microbiome profiles |
| title_full_unstemmed | Recurrent Clostridium difficile infection associates with distinct bile acid and microbiome profiles |
| title_short | Recurrent Clostridium difficile infection associates with distinct bile acid and microbiome profiles |
| title_sort | recurrent clostridium difficile infection associates with distinct bile acid and microbiome profiles |
| url | http://hdl.handle.net/1721.1/109870 https://orcid.org/0000-0002-8033-8380 https://orcid.org/0000-0001-8294-9364 |
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