Gut microbiota-regulated glutathione metabolic rhythms restore obesity-induced colonic inflammato… — Gut microbes (2026)

Resumo clínico (PT)

Estudo experimental que explora a ligação entre ritmos circadianos, microbiota intestinal e inflamação colónica na obesidade induzida por dieta hiperlipídica. A suplementação com fruto-oligossacarídeos restaurou ritmicidade microbiana e oscilações de metabolismo da glutationa, atenuando inflamação colónica independentemente do relógio circadiano central. Transplante fecal e omics integrados sugerem a glutatione colónica (via Gclc) como mediador downstream; o knockdown de Gclc anulou o efeito restaurador. Implicação: a obesidade pode desorganizar eixos microbiota–metabolismo com impacto inflamatório rítmico; intervenções que recuperem ritmos microbianos são hipótese mecanística relevante, ainda sem tradução clínica directa.

Abstract (original)

Obesity disrupts circadian inflammatory rhythms, a defining feature of metabolic syndrome. However, the mechanisms connecting microbial and host circadian communication remain unclear. By using the fermentable fiber fructo-oligosaccharide (FOS) to restore microbial rhythmicity, we found that a high-fat diet (HFD) disrupts microbiota-regulated oscillations in glutathione metabolism, thereby dampening colonic inflammatory rhythms independently of the core clock machinery. Fecal microbiota transplantation (FMT) further supported a causal role for rhythmic fecal microbial signals in restoring inflammatory oscillations. Integrated multi-omics analysis highlighted circadian glutathione metabolism as a prominent candidate pathway linking microbial rhythmicity to host inflammatory oscillations. Importantly, colon-specific knockdown of Gclc , the rate-limiting enzyme in glutathione synthesis, abolished the restorative effects of microbial rhythms, functionally positioning host glutathione metabolism as a critical downstream mediator. Collectively, our study supports the existence of a microbiota-glutathione axis that contributes to the regulation of colonic inflammatory rhythms, uncovering a new chronobiological layer of microbial control over host inflammation.