HMGB1 mediates microbiome-immune axis dysregulation underlying reduced neutralization capacity in obesity-related...

Area of Science:

• Immunology
• Microbiology
• Infectious Diseases

Background:

• Obesity is a known risk factor for post-acute sequelae of SARS-CoV-2 infection (PASC), commonly known as long-COVID.
• The precise mechanisms linking obesity to PASC remain inadequately understood, necessitating further investigation into immune and microbiome alterations.

Purpose of the Study:

• To investigate the relationship between obesity, immune dysregulation, and gut microbiome changes in patients experiencing PASC.
• To identify potential biomarkers and therapeutic targets for obesity-associated PASC.

Main Methods:

• A 6-week longitudinal study involving weekly symptom tracking and blood sample collection for biomarker and immune cell profiling.
• Plasma samples analyzed using ELISA and Luminex assays.
• Gut microbiome composition assessed via 16S-based metagenomic sequencing of stool samples.

Main Results:

• Obesity-related PASC was associated with a persistent proinflammatory state and diminished adaptive immunity.
• Reduced gut microbial diversity was observed in patients with obesity-related PASC.
• Elevated high mobility group box 1 (HMGB1) protein levels in plasma correlated with impaired viral neutralization, particularly in obese individuals.

Conclusions:

• Sustained inflammation, reduced adaptive immunity, and gut dysbiosis are key features of obesity-associated PASC.
• HMGB1 protein emerges as a potential biomarker for PASC risk assessment and may play a role in therapeutic strategies.
• Targeting HMGB1 signaling could offer a novel approach for managing PASC in obese patients.