Inflammatory disease microbiomes share a functional pathogenicity predicted by C-reactive protein.

Area of Science:

• Microbiome research
• Immunology
• Gastroenterology

Background:

• The human gut microbiome plays a crucial role in health and disease.
• Dysbiosis of the gut microbiome is implicated in various inflammatory conditions.
• Understanding microbiome functions is key to developing novel therapeutic strategies.

Purpose of the Study:

• To investigate the disease-specific and cross-disease functions of the human gut microbiome.
• To identify how different human microbiomes influence inflammatory conditions in a host.
• To explore the relationship between microbiome composition and host systemic inflammation.

Main Methods:

• Colonization of germ-free mice with over 100 human fecal microbiomes from individuals with various inflammatory diseases.
• Assessment of inflammatory phenotypes (arthritis, colitis, neuroinflammation) in colonized mice.
• Correlation analysis between mouse inflammatory disease and host systemic inflammation markers (e.g., C-reactive protein) in human donors.

Main Results:

• Common inflammatory phenotypes were observed across different diseases, driven by microbiomes from individuals with intestinal inflammation or inflammatory arthritis.
• Distinct microbiome functions specific to multiple sclerosis patients were identified.
• Inflammatory disease severity in mice correlated with systemic inflammation levels in human donors, indicating a link between donor and host inflammation.

Conclusions:

• Human gut microbiomes harbor both shared and disease-specific pathogenic functions.
• Microbiome-driven inflammation mirrors disease features, including therapeutic targets and systemic inflammation status.
• These findings suggest that the gut microbiome is a significant factor in shaping and driving inflammatory responses across multiple diseases.