Effects of Time-Restricted Eating (Early and Late) Combined with Energy Restriction vs. Energy Restriction Alone on the Gut Microbiome in Adults with Obesity.

Early time-restricted eating combined with energy restriction (eTRE + ER) has been shown to reduce fat mass, diastolic blood pressure (DBP) and fasting glucose more effectively than late TRE with energy restriction (lTRE + ER) or energy restriction (ER) alone. Given the gut microbiome's sensitivity to circadian rhythms, we examined whether adding TRE, particularly eTRE, to ER alters gut microbiota composition beyond ER alone, and whether such effects persist during follow-up. We analysed anthropometric, biochemical and gut microbiome data from 76 participants at baseline and after a 3-month intervention (eTRE + ER: = 33; lTRE + ER: = 23; ER: = 20). Follow-up microbiome data 6-months after the end of intervention were available for 43 participants. Gut microbiota composition was assessed via 16S rRNA gene sequencing of stool samples. No significant between-group differences in beta diversity were observed over time. However, changes in alpha diversity differed significantly across groups at the end of the intervention (Shannon: F = 5.72, < 0.001; Simpson: F = 6.72, < 0.001; Richness: F = 3.99, = 0.01) and at follow-up (Richness: F = 3.77, = 0.02). lTRE + ER led to the greatest reductions in diversity post intervention, while ER was least favourable during follow-up. Although no significant between-group differences were observed at the phylum level either at the end of the intervention or during follow-up, only the eTRE + ER group exhibited a significant decrease in Bacillota and an increase in Bacteroidota during follow-up. At the genus level, differential abundance analysis revealed significant shifts in taxa such as , , and other genera within the and families. In the eTRE + ER, and increased, while in other groups decreased. Notably, the changes in were negatively correlated with fasting glucose, while the increase in was inversely associated with DBP; however, both associations were weak in strength. : eTRE + ER may promote beneficial, lasting shifts in the gut microbiome associated with improved metabolic outcomes. These results support further research into personalized TRE strategies for treatment of obesity.