Aging-induced Alternation in the Gut Microbiota Impairs Host Antibacterial Defense

Area of Science:

• Microbiology
• Immunology
• Gerontology

Background:

• Older adults exhibit heightened susceptibility and mortality to bacterial infections.
• The precise reasons for this increased vulnerability remain incompletely understood.
• Gut microbiota alterations are increasingly implicated in age-related health declines.

Purpose of the Study:

• To investigate the role of commensal bacteria in age-related susceptibility to bacterial infections.
• To identify mechanisms by which gut microbiota influences host defense in aging.
• To explore potential therapeutic targets for ameliorating age-associated immune dysfunction.

Main Methods:

• Comparative analysis of gut microbiota composition in aged and young mice, and aged humans.
• Colonization experiments with Parabacteroides goldsteinii in aged mice.
• Metabolomic profiling to identify protective compounds.
• Molecular assays to elucidate the mechanism of action of identified compounds.
• Gene identification using bacterial homologous recombination.

Main Results:

• Aging is associated with a reduction in Parabacteroides goldsteinii in both mice and humans.
• Colonization with live P. goldsteinii protects aged mice against bacterial infections.
• P. goldsteinii produces apigenin, which corrects bacterial clearance defects in aged mice.
• Apigenin directly interacts with Fgr kinase, enhancing macrophage phagocytosis via the Cdc42/Rac1 pathway.
• The gene ampB is identified as crucial for apigenin synthesis in P. goldsteinii.

Conclusions:

• Reduced P. goldsteinii in aging contributes to impaired bacterial defense.
• The gut microbiota-derived compound apigenin can restore aging-associated antibacterial immunity.
• The microbiota-apigenin-Fgr signaling axis presents a novel therapeutic strategy for enhancing immunity in older adults.