Diet Modification and Not Timed Feeding Strategies Result in Intestinal Microbiome Alterations (P21-030-19)

Abstract

Abstract Objectives Time-restricted feeding strategies have been shown to normalize obesity parameters, even under high fat feeding conditions. The objective of this study is to examine whether timed feeding alters parameters of gut health or intestinal microbiome composition. Methods C57BL/6 male mice were randomized to Chow or a high fat diet (HFD) for 6 weeks, followed by a switch from HFD to 1) Chow (sChow), 2) Purified Vegan – Daniel Fast (DF), 3) HFD ad lib, 4) HFD time restricted (TRF), 5) HFD alternative day fasting (ADF), or 6) HFD 60% caloric restriction (CR) for an additional 8 weeks. Results We observed that body mass gain was reduced for all intervention groups (P ≤ 0.0001). Small intestinal length and cecal weight were increased in Chow, sChow and DF (P ≤ 0.02), while total cecal short chain fatty acid (SCFA) concentration was non-significantly increased for all groups consuming the HFD. Proprionate was specifically increased in the Chow, sChow and DF groups (P ≤ 0.02). Chow fed microbiota remained stable in taxonomic composition and alpha diversity (Shannon diversity index) throughout the study. HF fed microbiota displayed lower alpha diversity along with reduced phylum levels of Bacteroidetes and increase Firmicutes. Animals switched from HF to Chow demonstrated a rapid transition in taxonomic composition, alpha, and beta diversity that initially resembled HF, but clustered closely with Chow by weeks 4 and 8 of intervention. After 8 weeks on the respective dietary protocols, alpha diversity of the DF was most similar to Chow fed animals and also resulted in the largest increase in Bacteriodetes and largest decrease in Firmicutes. Beta diversity (weighted UniFrac) showed Chow, sChow, and DF clustered together, while high fat fed groups (HF, CR, ADF, and TRF) clustered. Compared with HF controls, CR and TRF led to a relative increase in the classes Clostridia, Deferribacteres and Deltaproteobacteria. The taxonomic composition and alpha diversity of ADF fasting resembled HF under fed conditions, while ADF under fasting conditions more closely resembled CR and TRF. Conclusions In conclusion, timed feeding on a high fat diet did not result in significant changes in the microbiome, demonstrating that diet, and not fasting is the major determinant for microbiome composition. Funding Sources University of Memphis & Children's Foundation Research Institute, Memphis.