Yanfei Chen1, Jing Guo1, Guirong Qian1, Daiqiong Fang1, Ding Shi1, Lihua Guo1, Lanjuan Li1. 1. State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China.
Abstract
BACKGROUND: Bacterial translocation from the gut plays an important role in the pathophysiology of acute-on-chronic liver failure (ACLF). However, gut dysbiosis in ACLF was not widely documented in previous studies. AIM: This research characterized the fecal microbiota in patients with ACLF and analyzed the temporal stability of gut microbiota during illness. METHODS: Fecal microbiota of 79 ACLF patients (42 patients were followed in the next 4 weeks after the first visit for longitudinal study) and 50 healthy controls was analyzed by 16S ribosomal DNA pyrosequencing. RESULTS: There was a marked difference between the ACLF group and the control group. The overall microbial diversity and richness were significantly lower in ACLF than in controls. ACLF patients had lower abundance of Bacteroidaceae, Ruminococcaceae, and Lanchnospiraceae, but higher abundance of Pasteurellaceae, Streptococcaceae, and Enterecoccaceae. The relative abundance of Lachnospiraceae was obviously decreased in ACLF patients with hepatic encephalopathy. The gut microbiota kept relatively stable in a short term after the onset of ACLF. The use of antibiotics only showed moderate impacts on the gut microbiota. The relative abundance of Pasteurellaceae and Model of End Stage Liver Disease score were independent factors predicting mortality rate. Network analysis comparison showed robust correlations between specific bacterial families (Ruminococcaceae and Lachnospiraceae) and inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor alpha, IL-2) in ACLF patients. CONCLUSIONS: These data suggest gut dysbiosis in ACLF and its predictive value for mortality. The results thus open up the possibility of designing diagnostic biomarkers and targeted probiotics aimed at decreasing mortality in ACLF.
BACKGROUND: Bacterial translocation from the gut plays an important role in the pathophysiology of acute-on-chronic liver failure (ACLF). However, gut dysbiosis in ACLF was not widely documented in previous studies. AIM: This research characterized the fecal microbiota in patients with ACLF and analyzed the temporal stability of gut microbiota during illness. METHODS: Fecal microbiota of 79 ACLF patients (42 patients were followed in the next 4 weeks after the first visit for longitudinal study) and 50 healthy controls was analyzed by 16S ribosomal DNA pyrosequencing. RESULTS: There was a marked difference between the ACLF group and the control group. The overall microbial diversity and richness were significantly lower in ACLF than in controls. ACLF patients had lower abundance of Bacteroidaceae, Ruminococcaceae, and Lanchnospiraceae, but higher abundance of Pasteurellaceae, Streptococcaceae, and Enterecoccaceae. The relative abundance of Lachnospiraceae was obviously decreased in ACLF patients with hepatic encephalopathy. The gut microbiota kept relatively stable in a short term after the onset of ACLF. The use of antibiotics only showed moderate impacts on the gut microbiota. The relative abundance of Pasteurellaceae and Model of End Stage Liver Disease score were independent factors predicting mortality rate. Network analysis comparison showed robust correlations between specific bacterial families (Ruminococcaceae and Lachnospiraceae) and inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor alpha, IL-2) in ACLF patients. CONCLUSIONS: These data suggest gut dysbiosis in ACLF and its predictive value for mortality. The results thus open up the possibility of designing diagnostic biomarkers and targeted probiotics aimed at decreasing mortality in ACLF.
Authors: Jasmohan S Bajaj; Leroy R Thacker; Andrew Fagan; Melanie B White; Edith A Gavis; Phillip B Hylemon; Robert Brown; Chathur Acharya; Douglas M Heuman; Michael Fuchs; Swati Dalmet; Masoumeh Sikaroodi; Patrick M Gillevet Journal: JCI Insight Date: 2018-03-08
Authors: Jasmohan S Bajaj; Jacqueline G OʼLeary; Puneeta Tandon; Florence Wong; Guadalupe Garcia-Tsao; Patrick S Kamath; Scott W Biggins; Jennifer C Lai; Hugo E Vargas; Benedict Maliakkal; Michael B Fallon; Paul J Thuluvath; Ram M Subramanian; Leroy R Thacker; K Rajender Reddy Journal: Am J Gastroenterol Date: 2019-07 Impact factor: 10.864
Authors: Jasmohan S Bajaj; Andrew Fagan; Melanie B White; James B Wade; Phillip B Hylemon; Douglas M Heuman; Michael Fuchs; Binu V John; Chathur Acharya; Masoumeh Sikaroodi; Patrick M Gillevet Journal: Am J Gastroenterol Date: 2019-07 Impact factor: 10.864
Authors: Jasmohan S Bajaj; Genta Kakiyama; I Jane Cox; Hiroshi Nittono; Hajime Takei; Melanie White; Andrew Fagan; Edith A Gavis; Douglas M Heuman; Ho Chong Gilles; Phillip Hylemon; Simon D Taylor-Robinson; Cristina Legido-Quigley; Min Kim; Jin Xu; Roger Williams; Masoumeh Sikaroodi; William M Pandak; Patrick M Gillevet Journal: Liver Transpl Date: 2018-05-13 Impact factor: 5.799
Authors: Sara Blasco-Algora; José Masegosa-Ataz; María Luisa Gutiérrez-García; Sonia Alonso-López; Conrado M Fernández-Rodríguez Journal: World J Gastroenterol Date: 2015-11-14 Impact factor: 5.742