AUTHOR=Gul Farzana , Herrema Hilde , Ameer Aqsa , Davids Mark , Nasir Arshan , Gerasimidis Konstantinos , Ijaz Umer Zeeshan , Javed Sundus TITLE=Dietary composition and fasting regimens differentially impact the gut microbiome and short-chain fatty acid profile in a Pakistani cohort JOURNAL=Frontiers in Systems Biology VOLUME=Volume 5 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/systems-biology/articles/10.3389/fsysb.2025.1622753 DOI=10.3389/fsysb.2025.1622753 ISSN=2674-0702 ABSTRACT=PurposeFasting is known to have beneficial effects on human physiology and health due to changes in gut microbiota and its associated metabolites. We investigated the effects of intermittent and Ramadan fasting on the gut microbial composition, diversity, and short-chain fatty acid (SCFA) profile in a Pakistani population.MethodsPaired fecal samples—a total of 29 for Ramadan fasting (divided into three groups, before and after completion and after 3 months) and 22 for intermittent fasting (divided into two groups, day 1 and day 10)—were collected for both 16S rRNA microbiome profiling and SCFA analysis. Study volunteers also provided a detailed questionnaire about the dietary regimen before and during the fasting period. Descriptive statistics were applied to ascertain variations in the gut microbiome and SCFAs attributable to changes in food consumption during fasting.ResultsRamadan fasting increased the bacterial taxonomic and functional diversity and decreased the abundance of certain harmful microbes such as Blautia, Haemophilus, Desulfovibrio, Lachnoclostridium, and Porphyromonas. Intermittent fasting showed increased abundance of Prevotella, Lactobacillus, and Anaerostipes. Ramadan fasting also led to a significant increase in SCFAs including C7, iC4, and iC6, accounting for variability in microbial composition and phylogeny, respectively. In intermittent fasting, C5, iC5, and iC6 contributed to variability in microbial composition, phylogeny, and function, respectively.ConclusionBoth fasting regimens impacted gut microbiome and metabolic signatures, but Ramadan fasting showed a more drastic effect due to the 30 days compliance period and water restriction than intermittent fasting. Ramadan fasting also improved metabolic health by increasing the abundance of SCFA-producing microbes. With Ramadan fasting, most microbial taxa reverted to their prefasting state after resumption of normal feeding patterns with few exceptions, indicating impact on microbial niche creation with prolonged fasting regimens that benefit Enterococcus, Turibacter, and Klebsiella colonization. The dietary regimen adopted during fasting, especially the consumption of high-fat-content food items, accounted for persistent gut microbial changes.