Clinical impact of microbiome in patients with decompensated cirrhosis

Table 1 Published studies regarding microbiome over cirrhotic patients

Study	Analysis	Conclusion
Chen et al[10], 2011	36 patients with liver cirrhosis and 24 healthy controls; analysis of fecal microbial community	Fecal microbial communities are distinct in patients with cirrhosis compared with healthy individuals. The prevalence of potentially pathogenic bacteria, such as Enterobacteriaceae and Streptococcaceae, along with the reduction of beneficial populations such as Lachnospiraceae in patients with cirrhosis may affect prognosis
Bajaj et al[11], 2012	60 patients with cirrhosis (24 patients without HE/36 with HE) and 17 age-matched healthy controls; stool and colonic mucosal microbiome analysis, linkage of them with changes in peripheral inflammation and cognition	There was higher abundance of autochthonous genera and a lower abundance of potentially pathogenic ones in controls compared with cirrhotic patients’ mucosa. Significant change was recorded in the microbiome of the mucosa compared with stool. In general HE patients had less “healthy” microbiome
Bajaj et al[30], 2012	25 patients (17 HE and 8 without HE) and 10 controls; fecal microbiota analysis	Cirrhosis, especially when complicated with HE, is associated with significant alterations in the stool microbiome compared with healthy individuals. Specific bacterial families (Alcaligeneceae, Porphyromonadaceae, Enterobacteriaceae) are strongly associated with cognition and inflammation in HE.
Bajaj et al[29], 2014	15 patients with compensated cirrhosis and 15 age-matched healthy controls; stool microbiota profiling before (pre) and after PPI	Significant microbiota change was seen in both controls and cirrhotics after omeprazole. Omeprazole is associated with a microbiota shift and functional change in the distal gut in patients with compensated cirrhosis that could set the stage for bacterial overgrowth
Bajaj et al[12], 2014	219 cirrhotics (121 compensated outpatients, 54 decompensated outpatients, 44 inpatients) and 25 age-matched controls); stool analysis and introduction of the cirrhosis dysbiosis ratio (CDR)	Relative stability of the microbiota and CDR over time within cirrhotics whose disease remained unchanged. Microbiota changed when the underlying disease worsened in HE and infections reflected by CDR reduction. Associations of increased dysbiosis, with lower CDR and higher gram-negative taxa relative abundance. CDR for controls was significantly higher compared to all cirrhotic patients
Kakiyama et al[45], 2014	19 healthy, 6 drinkers without liver disease, and 78 cirrhotic (compensated and decompensated) patients; fecal and serum bile acids (BA), serum endotoxin, and stool microbiota analysis	Bile acids affect the composition of the intestinal microbiota Higher total BA pool in alcoholic cirrhotics could lead to a higher substrate for microbiota. Inflammation and gut barrier injury in alcoholic liver disease
Qin et al[13], 2014	98 cirrhotic patients and 83 healthy controls; gene catalogue of gut microbes analysis	Patients with liver cirrhosis have a less “healthy” gut microbiome, enriched with Veillonella, Streptococcus, Clostridium. Healthy individuals’ microbiome was enriched with autochthonous species (Lachnospiraceae and Ruminococcaceae). Proof that the major change of the gut microbiota in patients with liver cirrhosis, is mainly because of a massive invasion of the gut by oral bacterial species
Bajaj et al[14], 2015	102 patients with cirrhosis (with/without HE) and 32 age-matched healthy controls; stool and saliva microbiome analysis along with evaluation of systemic and salivary inflammatory response	Dysbiosis, represented by reduction in autochthonous bacteria (Lachnospiraceae, Ruminococcaceae, and Clostridiales XIV), is present in both saliva and stool in patients with cirrhosis, compared to controls. Stool cirrhosis dysbiosis ratio (Lachnospiraceae + Ruminococcaceae + Clostridiales Incertae Sedis XIV + Veillonelllaceae/Enterobacteriaceae + Bacteroidaceae) was significantly lower in patients with cirrhosis. Salivary microbiota dysbiosis ratio (Lachnospiraceae + Ruminococcaceae + Clostridiales Incertae Sedis XIV/Streptococcaceae), was lower in patients with cirrhosis, compared to controls
Bajaj et al[36], 2015	278 cirrhotics (39% with HE, 31% with DM); stool microbial analysis and 72 underwent mucosal analyses	Cirrhotic subjects who required non-elective 90 d hospitalization had a different microbial profile DM in the presence of cirrhosis alters the mucosal and stool microbiota compared to cirrhotics without DM, it does not add to the 90 d hospitalization risk
Chen et al[35], 2015	79 ACLF patients and 50 controls; fecal microbiota analysis	ACLF patients had lower abundance of Bacteroidaceae, Ruminococcaceae, and Lanchnospiraceae, but higher abundance of Pasteurellaceae, Streptococcaceae, and Enterecoccaceae. Abundance of Lachnospiraceae was decreased in ACLF patients with HE. Gut dysbiosis in ACLF has predictive value for mortality and could represent diagnostic biomarker
Ling et al[16], 2015	10 CHB patients, 10 patients with HBV-associated compensated liver cirrhosis (LC), and 10 healthy controls (HC)	Differences in the compositions of the oral microbiota revealed the dysbiosis involved in the development of HBV-CLD
Lu et al[17], 2016	35 early liver carcinoma (LC) patients with cirrhosis and 25 matched healthy subjects; study of microbiome of the tongue coat	Certain key bacterial species may characterize LCT microbiota; Oribacterium and Fusobacterium could distinguish LC patients from healthy subjects. Microbiota dysbiosis of tongue coat in LC patients, may provide novel and non-invasive potential diagnostic biomarker of LC.
Ahluwalia et al[31], 2016	40 healthy controls and 147 cirrhotics (85 cirrhotic patients had HE); stool samples and brain MRI assessment	Effort to understand the role of impaired gut-liver-brain axis in cirrhosis. Gut microbial changes are linked with systemic inflammation, ammonia and ultimately with neuronal and astrocytic dysfunction in cirrhotic patients, especially those with HE
Chen et al[15], 2016	30 cirrhotic patients and 28 healthy subjects; study of the duodenal microbiome	Duodenal mucosa microbiota in cirrhotic patients is dramatically different from healthy controls. The duodenum dysbiosis might be related to alterations of oral microbiota and changes in duodenal micro-environment. Possible associations between small intestinal microbiota of oral origins and hepatic encephalopathy.
Santiago et al[34], 2016	27 patients (13 with ascites and 14 without ascites), 17 healthy controls; stool (n = 17) and serum (n = 7) microbiome analysis	Patients with ascites have a greater deterioration of the intestinal barrier integrity, also a higher degree of microbial translocation than those without ascites, thus leading to a higher microbial diversity and higher concentration of lipopolysaccharide binding protein (LBP) in serum Specific serum microbiome is linked to the presence of ascites Alteration of the serum and fecal microbiome composition be considered indicators of cirrhosis progression

HE: Hepatic encephalopathy; PPI: Proton-pump inhibitor; CDR: Cirrhosis dysbiosis ratio; ACLF: Acute-on-chronic liver failure; HBV: Hepatitis B virus; CLD: Chronic liver disease; DM: Diabetes mellitus.