Short-Term Dietary Restriction Potentiates an Anti-Inflammatory Circulating Mucosal-Associated Invariant T-Cell...

Area of Science:

• Immunology
• Microbiology
• Nutritional Science

Background:

• Short-term protein-calorie dietary restriction (StDR) is a potential preoperative strategy to reduce inflammation.
• The interplay between StDR, the gut microbiome, and systemic immunity is not fully understood.
• Mucosal-associated invariant T-cells (MAITs) link innate and adaptive immunity and are sensitive to gut microbial alterations.

Purpose of the Study:

• To investigate the impact of StDR on MAIT cell transcriptomics.
• To analyze changes in gut microbial composition during StDR.
• To explore the relationship between StDR, gut microbiota, and MAIT cell responses.

Main Methods:

• Single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) from healthy volunteers undergoing 4 days of StDR.
• Sequencing of stool samples to assess gut microbial species abundance.
• Collection of blood and stool samples before, during, and after the dietary intervention.

Main Results:

• MAIT cells constituted 2.4% of PBMCs.
• StDR led to downregulation of MAIT activation and pro-inflammatory genes (e.g., CD69, IL1, IL6, TNFα), and upregulation of anti-inflammatory IL10 signaling genes.
• A decrease in the abundance of MAIT-stimulating *Bacteroides* species was observed during StDR.

Conclusions:

• StDR may induce an anti-inflammatory MAIT cell phenotype.
• This immunophenotypic shift may be mediated by alterations in T-cell receptor-dependent signaling.
• Changes in gut microbial composition during StDR could contribute to the observed anti-inflammatory immune response.