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We identified glutathione metabolism as a prominent rhythmic pathway linking microbial rhythmicity to host inflammatory oscillations.Citation 61 This interpretation is consistent with previous studies showing that glutathione levels, GCL activity, and Gclc-related biosynthetic programs exhibit circadian variation and are under clock-dependent regulation.Citation 62 Integrated multi-omics analyzes combining transcriptomic and metabolomic profiling revealed that glutathione metabolic oscillations were preserved in LFD and HFD-FOS groups but absent in HFD-fed mice, with the glutamate-cysteine ligase catalytic subunit ( Gclc ) displaying particularly robust circadian expression patterns that correlated with microbial diurnal dynamics.Citation 63 , Citation 64 These oscillations encompassed both glutathione synthesis and regeneration, forming a coherent metabolic rhythm aligned with microbial ecological shifts.Citation 65 Functional validation through colon-specific Gclc knockdown showed that glutathione synthesis is functionally required for maintaining inflammatory rhythms, as its inhibition markedly dampened rhythmic amplitude and abolished the restorative effects of microbial rhythmicity

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The function of nitric oxide in wound repair: inhibition of inducible nitric oxide-synthase severely impairs wound reepithelialization