Short-term dietary changes can result in mucosal and systemic immune depression

Area of Science:

• Immunology
• Nutrition Science
• Microbiology

Background:

• Omnivores, including humans, often prefer high-fat, energy-dense foods over plant-based diets, especially for short durations.
• The health implications of such short-term dietary patterns remain incompletely understood.

Purpose of the Study:

• To investigate the immunological consequences of short-term dietary shifts towards energy-dense foods.
• To determine the impact on intestinal microbiota, immune cell function, and susceptibility to infection.

Main Methods:

• Utilized mouse models subjected to cyclical 'feast diets' mimicking human social eating patterns.
• Assessed changes in mucosa-associated lymphoid tissues (MALT) and systemic immunity.
• Evaluated susceptibility to bacterial infections (Salmonella Typhimurium, Listeria monocytogenes) and immune response to a model antigen.
• Analyzed CD4+ T cell metabolism, mTOR activity, and the role of microbial fiber metabolites.
• Conducted dietary intervention studies with human volunteers.

Main Results:

• Short-term dietary switching impaired mucosal and systemic immunity, increasing infection susceptibility.
• Immune depression was linked to reduced CD4+ T cell metabolic fitness and impaired mTOR activity due to decreased fiber metabolites.
• Reintroducing dietary fiber restored T cell metabolism and immune functions.
• Human studies confirmed that short-term dietary changes affect CD4+ T cell functionality.

Conclusions:

• Transient dietary changes significantly impact immune system function, creating a window for pathogen invasion.
• Gut microbiota and fiber metabolites play a crucial role in maintaining immune homeostasis.
• Dietary interventions can modulate immune responses, highlighting the plasticity of the immune system.