Editor's Note: Most patients with acute-on-chronic liver failure (ACLF) exhibit varying degrees of cholestasis. Previous studies have shown that compared to standard medical treatment alone, the artificial liver support system (ALSS) can improve prognosis and extend survival time in ACLF patients. Additionally, research has confirmed gut microbiota dysbiosis in ACLF patients. However, the specific impact of ALSS on the gut microbiota composition in these patients remains unclear. Considering the complex interactions between gut microbiota, bile acids (BAs), and the liver, researchers conducted a study to elucidate the unique effects of ALSS on gut microbiota and serum BAs in ACLF patients. Furthermore, the study visualized the relationships between gut microbiota, serum BAs, and clinical outcomes in ACLF patients using correlation heatmaps, providing insights into potential therapeutic targets for ACLF. The study was recently published in Hepatology International.Background
ACLF patients often exhibit gut microbiota dysbiosis, and BAs can influence the composition of gut microbiota. Previous studies have indicated that ALSS can improve prognosis and extend survival time in ACLF patients, but the impact of ALSS on gut microbiota and serum BAs in these patients remains unclear.
Methods
Researchers conducted a prospective study involving 51 patients diagnosed with ACLF. Based on the use of ALSS during treatment, participants were divided into two groups: the standard medical treatment group (SMT group, n=19) and the ALSS combined with SMT group (ALSS group, n=32). Blood and stool samples were collected on the day of admission and 14 days after treatment. Healthy control subjects (HC group, n=8) were also recruited, and their stool samples were collected. Researchers performed 16S rRNA sequencing to analyze the gut microbiota and used ultra-high-performance liquid chromatography/mass spectrometry to measure serum BAs.
Results
Compared to the SMT group, patients in the ALSS group had higher liver inflammation markers, particularly alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (P < 0.05). Other indicators, such as age, total bilirubin, and MELD scores, showed no significant differences.
01. Impact of ALSS on Gut Microbiota
Alpha diversity analysis showed that Chao 1, Shannon, and Pielou_e indices in the ACLF group were significantly lower than those in the HC group. Compared to the SMT group, these indices were slightly higher in the ALSS group, but the differences were not statistically significant. Additionally, beta diversity analysis based on Bray-Curtis distance showed clear separation between the ACLF and HC groups on the PCo1 and PCo2 axes (Figure 1). There was no clear separation on the PCo1 axis between the SMT and ALSS groups, but there was some separation on the PCo2 axis.
Combining alpha and beta diversity analyses, the gut microbiota abundance and diversity in ACLF patients were decreased, and ALSS could partially improve gut microbiota dysbiosis in ACLF patients.
To further compare differences in gut microbiota composition among groups, researchers constructed a heatmap based on the average abundance data of the top 20 genera. The heatmap showed relatively higher abundances of beneficial genera in the ALSS group, such as Parabacteroides_B, Ligilactobacillus, Lactobacillus, and Phocaeicola_A.
Researchers then analyzed differences in species relative abundance at the genus level. Results indicated that, compared to the HC group, the ACLF group had increased relative abundances of Escherichia and Streptococcus and decreased relative abundance of Collinsella. This indicates changes in gut microbiota composition in ACLF patients, characterized by an increase in harmful bacteria and a decrease in beneficial bacteria. Comparing the ALSS and SMT groups, researchers observed higher relative abundances of Phocaeicola_A and Ligilactobacillus and lower relative abundance of Escherichia in the ALSS group. This indicates that ALSS has a regulatory effect on gut microbiota composition.
02. Impact of ALSS on Serum BAs
Researchers quantitatively analyzed the concentrations of 18 BAs in serum samples from ACLF patients before treatment (n=51) and 14 days after treatment (n=26). The top five BAs by concentration were glycocholic acid (GCA), glycochenodeoxycholic acid (GCDCA), taurochenodeoxycholic acid (TCDCA), taurocholic acid (TCA), and glycoursodeoxycholic acid (GUDCA), accounting for over 90% of total BA concentration. Principal component analysis showed greater sample separation in the post-treatment group compared to the pre-treatment group. Additionally, samples within the ALSS group were more clustered compared to the SMT group.
Compared to the pre-treatment group, the concentrations of cholic acid (CA), chenodeoxycholic acid (CDCA), and ursodeoxycholic acid (UDCA) were significantly increased in the post-treatment group (P < 0.05), while concentrations of TCDCA and GCDCA were decreased (P < 0.05). There were no significant differences in the concentrations of the remaining unconjugated and conjugated BAs, nor in total unconjugated and total conjugated BAs. Compared to the SMT group, the concentrations of UDCA, GUDCA, and total unconjugated BAs were significantly higher in the ALSS group (P < 0.05).
There were no significant differences in total primary and secondary BA concentrations between the pre-treatment and post-treatment groups. Similarly, there were no significant differences in total primary and secondary BA concentrations between the ALSS and SMT groups, indicating that ALSS did not significantly affect the overall composition of primary and secondary BAs.
Compared to the pre-treatment group, the total hydrophilic and hydrophobic BA concentrations were significantly reduced in the post-treatment group (P < 0.05), but the ratio of total hydrophilic to total hydrophobic BAs increased (P < 0.05). There were no differences in the concentrations of total hydrophobic and total hydrophilic BAs between the ALSS and SMT groups.
In summary, compared to SMT, ALSS effectively increased the concentrations of UDCA and GUDCA.
Conclusion
ACLF patients exhibit gut microbiota dysbiosis and abnormal BA profiles. Compared to SMT alone, ALSS combined with SMT is more effective in regulating gut microbiota dysbiosis and increasing UDCA and GUDCA concentrations. Correlation analysis showed a significant relationship between gut microbiota and BAs.
This study identified the characteristics of gut microbiota and serum BA composition in ACLF patients and emphasized the impact of ALSS on gut microbiota and serum BAs.
