Gut Ruminococcaceae levels at baseline correlate with risk of antibiotic-associated diarrhea

Xiaoqiong Gu; Jean X Y Sim; Wei Lin Lee; Liang Cui; Yvonne F Z Chan; Ega Danu Chang; Yii Ean Teh; An-Ni Zhang; Federica Armas; Franciscus Chandra; Hongjie Chen; Shijie Zhao; Zhanyi Lee; Janelle R Thompson; Eng Eong Ooi; Jenny G Low; Eric J Alm; Shirin Kalimuddin

doi:10.1016/j.isci.2021.103644

Gut Ruminococcaceae levels at baseline correlate with risk of antibiotic-associated diarrhea

iScience. 2021 Dec 16;25(1):103644. doi: 10.1016/j.isci.2021.103644. eCollection 2022 Jan 21.

Authors

Xiaoqiong Gu^{1

2}, Jean X Y Sim³, Wei Lin Lee^{1

2}, Liang Cui^{1

2}, Yvonne F Z Chan³, Ega Danu Chang^{1

2}, Yii Ean Teh³, An-Ni Zhang⁴, Federica Armas^{1

2}, Franciscus Chandra^{1

2}, Hongjie Chen^{1

2}, Shijie Zhao⁴, Zhanyi Lee^{1

2}, Janelle R Thompson^{5

6}, Eng Eong Ooi^{7

8

9}, Jenny G Low^{3

7

8}, Eric J Alm^{1

2

4

10

11}, Shirin Kalimuddin^{3

7}

Affiliations

¹ Antimicrobial Resistance Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, 1 Create Way, Singapore 138602, Singapore.
² Campus for Research Excellence and Technological Enterprise (CREATE), Singapore 138602, Singapore.
³ Department of Infectious Diseases, Singapore General Hospital, Academia Level 3, 20 College Road, Singapore 169856, Singapore.
⁴ Department of Biological Engineering, Massachusetts Institute of Technology, 21 Ames Street, Cambridge, MA 02142, USA.
⁵ Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
⁶ Asian School of the Environment, Nanyang Technological University, 62 Nanyang Drive, Singapore 637459, Singapore.
⁷ Program in Emerging Infectious Diseases, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.
⁸ Viral Research and Experimental Medicine Center, SingHealth Duke-NUS Academic Medical Centre (ViREMiCS), 20 College Road, Singapore 169856, Singapore.
⁹ Saw Swee Hock School of Public Health, National University of Singapore, 12 Science Drive 2, Singapore 117549, Singapore.
¹⁰ Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Building E25-321, Cambridge, MA 02139, USA.
¹¹ Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA.

Abstract

Antibiotic-associated diarrhea (AAD) affects a significant proportion of patients receiving antibiotics. We sought to understand if differences in the gut microbiome would influence the development of AAD. We administered a 3-day course of amoxicillin-clavulanate to 30 healthy adult volunteers, and analyzed their stool microbiome, using 16S rRNA gene sequencing, at baseline and up to 4 weeks post antibiotic administration. Lower levels of gut Ruminococcaceae were significantly and consistently observed from baseline until day 7 in participants who developed AAD. Overall, participants who developed AAD experienced a greater decrease in microbial diversity. The probability of AAD could be predicted based on qPCR-derived levels of Faecalibacterium prausnitzii at baseline. Our findings suggest that a lack of gut Ruminococcaceae influences development of AAD. Quantification of F. prausnitzii in stool prior to antibiotic administration may help identify patients at risk of AAD, and aid clinicians in devising individualized treatment regimens to minimize such adverse effects.

Keywords: Health sciences; Microbiome; Pathophysiology.