Our recent meta-analysis (Pham et al. 2024) on n=1,186 participants from 23 clinical trials highlights beneficial effects of increased short-chain fatty acid (SCFA) concentrations in improving insulin sensitivity. However, longitudinal changes in gut microbiome and SCFAs during the progression to obesity/diabetes are not well understood.
We aimed to capture longitudinal changes in gut SCFAs through two mouse models of diet-induced-obesity using high fat-diet (HFD) and dietary weight cycling, which comprised of 2-week oscillation between HFD and normal (chow) diet for 24 weeks (study-endpoint). Body weight, blood glucose, and faeces were collected weekly to bi-weekly, while serum and gut contents (n=16-20 animals/group; ~50% females) were collected at the study endpoint. Gut microbiome composition was determined using qPCR with specific bacterial primers. A non-derivitisable method was optimised to measure SCFAs from faeces and plasma samples on a Sciex LC-MS platform.
HFD and oscillating diet led to overweight/obesity. A glucose tolerance test at study endpoint demonstrated dysregulation in both groups relative to Controls. We observed a significant reduction in faecal SCFAs (acetate, propionate, and butyrate) in mice on HFD and oscillating diet compared to Chow diet (87.94%, p=0.00004 and 79.04%, p=0.0146, respectively) while longitudinal SCFA analysis demonstrated a steady reduction in HFD group compared to control for each SCFAs. Significant positive association between serum and faecal acetate (p=0.039); and serum and colon propionate (p=0.038), were observed.
This study is the first to longitudinally profile SCFAs in this long-term (2-weekly) dietary weight cycling animal model. These findings demonstrate that longer (2-weekly), but regularly intermittent consumption of HFD, may be equally worse as being on HFD for the time. These findings, validate some of our own (and other’s) findings on epigenetic regulation of gut incretin hormones by the food choices we make and reveal some of the therapeutic targets for obesity and type 2 diabetes.