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Author Spotlight: Investigating Bacteriophage-Induced Immune Responses in Gnotobiotic Mice
Published on: January 26, 2024
Impact of bacterial infections and spontaneous bacterial peritonitis prophylaxis on phage-bacterial dynamics in
Jasmohan S Bajaj1, Marcela Peňa Rodriguez2, Andrew Fagan1
1Division of Gastroenterology, Hepatology and NutritionVirginia Commonwealth University and Central Virginia Veterans Healthcare System Medical CenterVirginiaUSA.
Background And Aims:
Gut microbiota, including bacteria and phages, are altered in cirrhosis, but their role during infections and spontaneous bacterial peritonitis (SBP) prophylaxis is unclear. Our aim was determine metagenomic changes in gut bacteria; phages and their linkages centered around Gram-negative and Gram-positive pathobionts in patients with cirrhosis with/without infections or SBP prophylaxis.
Approach And Results:
We included uninfected (n = 231) and infected (n = 30, SBP n = 19 and urinary tract infection n = 11 before antibiotics) patients who gave stool for bacterial and phage metagenomics. We matched uninfected to infected patients 1:1 on a model for end-stage liver disease (MELD). We also analyzed subgroups of patients with ascites matched on an MELD (n = 73) to patients on SBP prophylaxis (n = 7) and then to SBP infection. Phage and bacterial taxa differences (DESeq2) and correlation networks centered around Escherichia coli and Enterococcus faecium were analyzed. Infections were mostly due to Enterobacteriaceae and Enterococcus spp. On metagenomics, higher fold changes of Enterobacteriaceae members, Enterococcus and Streptococcus spp., and Escherichia phages were seen in infected patients. Correlation networks showed more complex bacteria-phage linkages in infected patients compared with uninfected ones overall and centered around E. coli and E. faecium. SBP prophylaxis induced higher Gram-positive bacteria. In SBP, Enterococcus and Escherichia were higher versus ascites. Correlation networks around E. coli were complex in ascites but sparse with SBP prophylaxis, whereas the reverse was seen with E. faecium. Lytic phages and those associated with antibiotic resistance were correlated with E. faecium.
Conclusion:
In cirrhosis, there are significant changes in phage-bacterial linkages in infected patients and those on SBP prophylaxis compared to the remaining patients. SBP prophylaxis enriches complexity of E. faecium-centered but induces a collapse in E. coli-centered phage-bacterial correlations.
Insights
In cirrhosis patients, gut bacteria and phages shift during infection and spontaneous bacterial peritonitis (SBP) prophylaxis. These changes impact bacterial-phage interactions, particularly concerning Escherichia coli and Enterococcus faecium.
Area of Science:
- Gastroenterology
- Microbiology
- Infectious Diseases
Background:
- Cirrhosis alters gut microbiota, including bacteria and phages.
- The role of these alterations in infections and spontaneous bacterial peritonitis (SBP) prophylaxis remains unclear.
Purpose of the Study:
- To determine metagenomic changes in gut bacteria and phages.
- To analyze bacteria-phage linkages centered around Gram-negative and Gram-positive pathobionts in cirrhosis patients with or without infections or SBP prophylaxis.
Main Methods:
- Stool samples analyzed for bacterial and phage metagenomics from uninfected and infected cirrhosis patients.
- Patients matched by Model for End-Stage Liver Disease (MELD) score.
- Correlation networks analyzed for bacteria-phage linkages, focusing on Escherichia coli and Enterococcus faecium.
Main Results:
- Infected patients showed higher levels of Enterobacteriaceae, Enterococcus, Streptococcus spp., and Escherichia phages.
- Bacteria-phage correlation networks were more complex in infected patients.
- Spontaneous bacterial peritonitis (SBP) prophylaxis increased Gram-positive bacteria and altered phage-bacterial correlations around E. coli and E. faecium.
Conclusions:
- Cirrhosis patients exhibit significant changes in phage-bacterial linkages during infection and SBP prophylaxis.
- SBP prophylaxis enriches Enterococcus faecium-centered linkages but collapses Escherichia coli-centered correlations.
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