Gut microbiome and metabolome signatures in liver cirrhosis-related complications

Sharma, Satya Priya; Gupta, Haripriya; Kwon, Goo-Hyun; Lee, Sang Yoon; Song, Seol Hee; Kim, Jeoung Su; Park, Jeong Ha; Kim, Min Ju; Yang, Dong-Hoon; Park, Hyunjoon; Won, Sung-Min; Jeong, Jin-Ju; Oh, Ki-Kwang; Eom, Jung A; Lee, Kyeong Jin; Yoon, Sang Jun; Ham, Young Lim; Baik, Gwang Ho; Kim, Dong Joon; Suk, Ki Tae

doi:.0..

Original Article

Gut microbiome and metabolome signatures in liver cirrhosis-related complications

Satya Priya Sharma¹, Haripriya Gupta¹, Goo-Hyun Kwon¹, Sang Yoon Lee¹, Seol Hee Song¹, Jeoung Su Kim¹, Jeong Ha Park¹, Min Ju Kim¹, Dong-Hoon Yang¹, Hyunjoon Park¹, Sung-Min Won¹, Jin-Ju Jeong¹, Ki-Kwang Oh¹, Jung A Eom¹, Kyeong Jin Lee¹, Sang Jun Yoon¹, Young Lim Ham², Gwang Ho Baik^1,3, Dong Joon Kim^1,3, Ki Tae Suk^1,3

¹Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Republic of Korea 24253
²Department of Nursing Daewon University College Jecheon, Republic of Korea 27135
³Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Republic of Korea 24253

Correspondence :

Ki Tae Suk ,
Tel: +82-33-240-5826, Fax: +82-33-241-8064, Email: ktsuk@hallym.ac.kr

Received: May 10, 2024 Revised: July 24, 2024 Accepted: July 24, 2024
*Satya Priya Sharma and Jeoung Su Kim contributed equally to this work.

ABSTRACT

Background/Aims
Shifts in the gut microbiota and metabolites are interrelated with liver cirrhosis progression and complications. However, causal relationships have not been evaluated comprehensively. Here, we identified complication-dependent gut microbiota and metabolic signatures in patients with liver cirrhosis.
Methods
Microbiome taxonomic profiling was performed on 194 stool samples (52 controls and 142 cirrhosis patients) via V3-V4 16S rRNA sequencing. Next, 51 samples (17 controls and 34 cirrhosis patients) were selected for fecal metabolite profiling via gas chromatography mass spectrometry and liquid chromatography coupled to time-of-flight–mass spectrometry. Correlation analyses were performed targeting the gut- microbiota, metabolites, clinical parameters, and presence of complications (varices, ascites, peritonitis, encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, and deceased).
Results
Veillonella bacteria, Ruminococcus gnavus, and Streptococcus pneumoniae are cirrhosis-related microbiotas compared with control group. Bacteroides ovatus, Clostridium symbiosum, Emergencia timonensis, Fusobacterium varium, and Hungatella_uc were associated with complications in the cirrhosis group. The areas under the receiver operating characteristic curve (AUROCs) for the diagnosis of cirrhosis, encephalopathy, hepatorenal syndrome, and deceased were 0.863, 0.733, 0.71, and 0.69, respectively. The AUROCs of mixed microbial species for the diagnosis of cirrhosis and complication were 0.808 and 0.847, respectively. According to the metabolic profile, 5 increased fecal metabolites in patients with cirrhosis were biomarkers (AUROC > 0.880) for the diagnosis of cirrhosis and complications. Clinical markers were significantly correlated with the gut microbiota and metabolites.
Conclusion
Cirrhosis-dependent gut microbiota and metabolites present unique signatures that can be used as noninvasive biomarkers for the diagnosis of cirrhosis and its complications.

KeyWords: Microbiota; Metabolite; Biomarker; Cirrhosis; Complication