S802 Visceral Fat Reduction via Palatable Elemental Diet Is Linked to Microbial and Hormonal Shifts in Adults

Introduction: Elemental diets (EDs) are complete sources of nutrition used in various disorders. Recently palatable ED (PED) significantly improved microbial overgrowth symptoms and sustainably reduced body fat and visceral fat, though the underlying physiological mechanisms remain unclear. Given the gut microbiome and gut-derived metabolic hormones as key factors, we investigated whether changes in stool microbes and circulating hormones correlate with sustained weight loss after PED. Methods: Adult subjects consumed 2 weeks of exclusive eucaloric oral PED (mBIOTA Elemental, NCT05978973) and were followed for 2 weeks upon reintroduction of regular diet. Blood was collected before PED (baseline), during PED, and at trial’s end for metabolic hormones (MILLIPLEX, Millipore-Sigma). Stool was collected for quantitative shotgun sequencing. DNA was extracted, sequenced, de-hosted, and analyzed using Kraken2 and CLC Microbial Module (Qiagen). Results: Three hundred and thirty subjects were included (63.3% women, age 45.9 ± 14.5 years). The mean percentages of visceral fat loss during PED and post-PED were 9.6 ± 11.0% (P < 0.001) and 11.2 ± 12.8% (P < 0.001), respectively. The stool microbiome underwent significant changes during PED and reset, at least in part, to a similar profile observed at baseline (PERMANOVA, P < 0.0001. At baseline, the microbial profile primarily correlated with body and visceral fat (P = 0.002) and, interestingly, with circulating glucagon-like peptide-1 (GLP-1) basal levels (P = 0.028). At the end of the PED and reintroduction of regular diet, bacterial profiles were associated with visceral fat loss (P = 0.007), in addition to circulating leptin (P = 0.013). The levels of circulating leptin fluctuated throughout the time points, with a significant drop during PED (P < 0.0001) and partial recovery after the reintroduction of regular diet (P = 0.04). Notably, no changes in circulating total GLP-1 were observed during PED (P = 0.2). However, significantly higher levels were observed after the reintroduction of regular diet (P = 0.03). As expected, GLP-1 was associated with weight loss at the end of the trial (R = 0.545, P = 0.002). Conclusion: Changes in the gut microbiome, modulated by PED, are associated with sustained visceral and body fat loss and elevated systemic levels of GLP-1 and leptin after reintroduction of regular diet. Further studies are warranted to understand the underlying cellular mechanism associated with these changes.