2509-P: Maternal Time-Restricted Feeding Alters the Gut Microbiota–Metabolite Rhythms and Counteracts Metabolic Deterioration in Adult Offspring

Introduction and Objective: Time-restricted feeding (TRF) optimizes energy metabolic efficiency by synchronizing the circadian rhythms, ultimately improving metabolism. However, its function in intergenerational effect remains poorly studied. Here, we tested whether maternal TRF could counteract metabolic deterioration in the adult offspring (PND112) induced by maternal high-fat diet. Methods: Mice were housed with the light following a 12:12 light/dark cycle (lights on at 07:00 = zeitgeber (ZT) 0). 4-week-old C57BL/6J female mice were given access to a normal diet (CTR), high-fat diet (HFD), and time-restricted high-fat diet (TRF). The diet intervention lasted from 9 weeks before pregnancy to the end of delivery. The litter sizes were homogenized to 6 pups for each dam within the first 3 post-natal days.16s sequencing and metabolomics were applied to the feces throughout 24 hours in offspring. dryR was used to characterize rhythmic patterns. Results: Maternal TRF significantly improved glucose tolerance (P < 0.01) and reduced the level of triglyceride (P < 0.01) in adult offspring compared to the maternal HFD group. The compositional and functional circadian rhythms of gut microbiota in the adult offspring were altered by maternal TRF. The dominant beneficial Lachnospiraceae showed circadian rhythm in the maternal control diet group, lost rhythm in the maternal HFD group, while gained rhythm in the maternal TRF group (Model 7, adjP < 0.05). Consistently, tryptophol exhibited the parallel change to the Lachnospiraceae (Model 7, adjP < 0.05), and significantly correlated with triglyceride across time (R = 0.68, adjP < 0.001). Conclusion: Taken together, we show that maternal TRF reprograms the metabolic rhythm and the gut microbiota rhythms, counteracting the metabolic dysfunction in the adult offspring. Disclosure L. Ding: None. Z. Xie: None. Y. Zhang: None. Y. Gao: None. Funding Beijing Natural Science Foundation (7254430), National Natural Science Foundation of China (82500979)