Microbiome Alterations Vary With Infections, Disease State

Three studies investigated and assessed changes in the gut microbiome among recipients of liver transplant, patients with hepatitis C virus (HCV), and patients with primary sclerosing cholangitis were presented at The American Association for the Study of Liver Diseases’ The Liver Meeting, held November 8 to 12, 2019 in Boston, Massachusetts.

Because the intestinal microbiome of recipients of liver transplant experiences a high burden of antibiotic exposure and severe iatrogenic pressure before and after the transplant, Pereira et al assessed multidrug-resistant microorganisms [MDRO] acquisition and gut microbiome changes in patients who have received liver transplantation.¹

In total, 28 patients who received a liver transplant were included. Rectal swabs used to sample stool were collected immediately pre- and post-transplant shortly before hospital discharge and tested for vancomycin-resistant enterococci (VRE) and fluoroquinolone-resistant enterococci (FQR), extended-spectrum beta-lactamase (ESBL), and carbapenemase-producing Gram-negative bacilli (GNB) by culture. All patients received carbapenem or an extended spectrum beta-lactam as surgical prophylaxis for ³3 days. The mean number of antibiotic days was 164.8 days in the 6 months pre-transplant and 27.1 days from transplant to discharge. Additional antibiotic exposures in pre- and post-transplant periods included vancomycin (20.5% and 38.2%, respectively) and fluoroquinolones (50% and 14.7%, respectively). Common antibiotic resistance genes were measured and data were compared with a cohort of healthy controls.

Results showed that patients in the pre-liver transplant exhibited worsened decreased microbial diversity and increased burden of antibiotic resistance genes during hospitalization after liver transplant when compared with baseline. For patients in the pre-liver transplant period, cultures detected VRE in 29.6% of samples, FQR GNB in 8.8%, and ESBL-producing GNB in 32.3%. Among patients in the posttransplant period, cultures demonstrated VRE in 36.3% of samples, FQR GNB in 3.5%, and ESBL-producing GNB in 32.1%. Further, the vancomycin resistance-associated gene (vanA) demonstrated approximately 80% accordance with culture-based VRE detection but was not detected in healthy patients.

Overall, the study authors concluded that, “The observed high MDRO carriage rates could underlie the known high burden of peri-[liver transplant] MDRO infections.”

Previous studies have shown that liver disease and infections such as HIV, HCV, hepatitis B, and influenza have been associated with complex microbial communities, as well as qualitative and quantitative dysbiotic changes in the gut microbiota. Therefore, Honda and colleagues investigated changes of gut microbiota before and after eradication of HCV.²

In total, 36 fecal samples from 12 patients who were treated with direct-acting antivirals (DAAs) for HCV were analyzed. The fecal samples were taken before treatment, at treatment end, and 24 weeks after end of treatment. No significant differences in diversity of gut microbiota among any patients between any period were observed. However, results showed a significantly increased relative abundance of Bacillus in patients at 24 weeks after the end of treatment compared with those before treatment. Further, there was a significant decrease in genes associated with immunodeficiency from pretreatment to 24 weeks post-treatment. The study authors concluded that, “Immunity and bile secretion related genes of gut microbiota could be associated with changes after eradication of HCV virus.”

A third study evaluated the microbiome of patients with primary sclerosing cholangitis.³ Researchers investigated the association of this illness with fecal and oral microbial profiles. Known for its frequent concurrence with inflammatory bowel disease (IBD), primary sclerosing cholangitis is a chronic, progressive cholestatic liver disease that can progress to cirrhosis, end-stage liver disease, hepatobiliary cancer, and/or colorectal cancer. Although several studies have reported dysbiosis of the gut microbiome in primary sclerosing cholangitis, little is known about the salivary microbiome of primary sclerosing cholangitis and primary sclerosing cholangitis-IBD. In total, 55 patients were included in the study: 28 patients with primary sclerosing cholangitis who also had IBD (n=18) and those who did not have concomitant IBD (n=17), as well as healthy volunteers matched for age and body mass index.

Results indicated that primary sclerosing cholangitis, with or without concomitant IBD, is a strong modulator of the microbial profile in the gut and saliva. Compared with healthy controls, 293 significantly altered gut microbes were found in patients with primary sclerosing cholangitis, including an overrepresentation of potentially pathogenic bacteria, decreased butyrate-producing beneficial bacteria, and an increased abundance of oral bacteria in the gut. A similar trend was demonstrated from the salivary samples.

“These results may represent an important therapeutic target in the management of [primary sclerosing cholangitis] in the future,” concluded the researchers.

Overall, these studies highlight the diversity of microbiome alterations in patients with various infection and disease states.

References

1. Pereira E, Christopher S, Zhang Q, et al. Changes to the gut microbiome and acquisition of multi-drug resistant microorganisms (MDROs) before and after liver transplantation (LT). Presented at: American Association for the Study of Liver Diseases: The Liver Meeting; November 8-12, 2019; Boston, MA. Abstract 1146.

2. Honda T, Ishigami M, Yamamoto K. Changes of microbiota after hepatitis C virus eradication. Presented at: American Association for the Study of Liver Diseases: The Liver Meeting; November 8-12, 2019; Boston, MA. Abstract 1941.

3. Lapidot L, Amir A, Ben-Simon S, et al. The salivary and fecal microbiome alterations in patients with primary sclerosing cholangitis. Presented at: American Association for the Study of Liver Diseases: The Liver Meeting; November 8-12, 2019; Boston, MA. Abstract 1925.