Ketogenic diet alleviates septic lung injury via microbial gut-lung axis.

Summary

A ketogenic diet reprograms the gut microbiota to enrich strains expressing an FMO that converts dietary oleic acid into azelaic acid, which traffics to the lung during sepsis to promote neutrophil apoptosis and expansion of MerTK+ macrophages, thereby resolving inflammation and mitigating lung injury.

Key Findings

• Ketogenic diet alleviates sepsis-induced lung injury via a gut–lung microbial axis.
• KD enriches Limosilactobacillus reuteri and Lactiplantibacillus plantarum in mice and humans.
• Specific strains express FMO that converts oleic acid into azelaic acid, which traffics to lung during sepsis.
• Azelaic acid promotes neutrophil apoptosis and expands MerTK+ macrophages to resolve inflammation.

Clinical Implications

Motivates evaluation of ketogenic-like nutritional strategies, FMO-bearing probiotics, or azelaic acid administration as adjuncts in sepsis, with careful safety and metabolic monitoring.

Limitations

• Human data appear observational; causal mechanisms are primarily demonstrated in mice.
• Safety and feasibility of ketogenic diets or metabolite supplementation in acute sepsis remain uncertain.

Future Directions

Test FMO-expressing probiotic strains or azelaic acid as therapeutics; define dietary parameters and patient subgroups for safe translation in sepsis.