Comparative Study of Gut Microbiome signatures in cirrhotics and their healthy donors undergoing Living Donor Liver Transplantation

Background and Aim: There is emerging evidence of gut dysbiosis in end-stage liver disease and its association with poor survival. We intend to study the gut microbiome profile in cirrhotics and compare with their liver donors as healthy individuals, when these patients are proceeding for living donor liver transplantation. Also, to understand the correlation of baseline gut microbiome with severity of liver disease. Methods: Fecal samples were collected from 14 patient donor pairs prior to transplant in this observational study. Genomic DNA was extracted from faecal samples using stool nucleic acid extraction kit and analysed by using 16s rRNA V3-V4 variable region next generation sequencing and metagenomics. Results: The mean age of recipients was 42.7±9.1 years and 37.6±9.7 years in donors. Mean MELD score was 19.4±7.5 and MELD-Na was 23.4±7.3. Predominant etiology was ethanol (50%) followed by MAFLD (21.4%). In phyla distribution, compared to recipients, donors had more Bacteroidetes (48.3%vs.31.9%, p=0.007), less Proteobacteria (7.71%vs.26.57%, p=0.001). At genera level, recipients compared to donors, showed less Prevotella (8.9%vs.29.4%), Lachnospira (4.16%vs.10.1%), more Enterobacteriaceae (20.1%vs.3.5%), p<0.05. Based on MELD score, recipients were categorized into three groups (<15,15-25,>25) and compared with donors. Proteobacteria, Enterobacteriaceae positively correlated and Prevotella, Lachnospira negatively correlated as the MELD score increased (p < 0.05). Based on aetiology, MAFLD>HCV>ethanol groups negatively correlated with Bacteroidetes and positively with Proteobacteria (p<0.05). Interestingly, as events of portal hypertension (SBP, bleed, HE, sepsis) increased, there was more Actinobacteria, Bacteroidetes/Firmicutes ratio, more Lactobacillaceae, Bifidobacteria and reduced Ruminococcus (p<0.05). Conclusions: Compared to donors, there was high abundance of pathogenic bacteria and low abundance of Bacteroides in recipients. This dysbiosis was more evident in increasing MELD scores and with more events of portal hypertension, which may affect prognosis. In conclusion, our study shows that in recipients compared to donors there is significant gut dysbiosis which can have implications on post-transplant outcomes.