Sequential Changes in the Mesenteric Lymph Node Microbiome and Immune Response during Cirrhosis Induction in Rats

Area of Science:

• Microbiology
• Immunology
• Gastroenterology

Background:

• The gut microbiota's role in cirrhosis evolution and immune response is unclear.
• Bacterial translocation from the gut may significantly impact cirrhosis outcomes.

Purpose of the Study:

• To investigate gut microbiome and immune response modifications during cirrhosis progression.
• To identify microbial shifts and their association with inflammation in cirrhosis.

Main Methods:

• Carbon tetrachloride (CCl4) induced cirrhosis in rats.
• Analyzed microbiome composition and load in various tissues (stool, ICCs, MLNs, blood, AFs) over 10 weeks.
• Measured cytokine production in MLNs and blood.

Main Results:

• Distinct microbiome compositions were observed in MLN, blood, and AF compared to stool and ICCs.
• Increased microbial load and pathobionts in MLN correlated with decompensated cirrhosis.
• Specific bacteria (Sutterella, Escherichia, "Candidatus Arthromitus") were associated with decompensation and elevated cytokines.
• "Candidatus Arthromitus" and Escherichia translocation from gut to AF/blood suggested.

Conclusions:

• Gut microbiome changes in distinct sites correlate with MLN microbial shifts and increased cytokine production.
• Evidence supports the gut-liver-immunity axis's role in cirrhosis progression.
• Microbiome compartmentalization and bacterial translocation are key factors in cirrhosis.