Ultra-processed, plant-based burgers (PB) and traditional comminuted-beef burgers (BB) share similar organoleptic characteristics, yet a knowledge gap exists in understanding how consumption of these divergent physical structures alters the lipemic response and gut microbiota. PB, comprised of highly refined ingredients, is formulated with no intact whole food structure, while BB entraps lipids throughout the myofibrillar protein network. PB presented significantly higher free fatty acid (FFA) bioaccessibility (28.2 ± 4.80 %) compared to BB (8.73 ± 0.52 %), as obtained from their FFA release profiles over digestion time after characterizing them with a modified logistic model (SLM), using the simulated TIM Gastro-Intestinal Model (TIM-1). Additionally, the rate of lipolysis, k, obtained from the SLM for PB (90% CI [0.0175, 0.0277] min-1) was higher than for BB (90% CI [0.0113, 0.0171] min-1). Using the Simulated Human Intestinal Microbial Ecosystem (SHIME®), the Firmicutes to Bacteroidetes ratio (F/B ratio) was significantly higher for PB than BB; and linear discriminant analysis effect size (LEfSe) showed Clostridium and Citrobacter were more highly represented in the microbial community for the PB feed, whereas BB feed differentially enriched Megasphaera, Bacteroides, Alistipes, and Blautia at the genus level. Additionally, short-chain fatty acid (SCFA) production was altered (p < 0.05) site-specifically in each colon vessel, which could be attributed to the available substrates and changes in microbial composition. Total SCFAs were significantly higher for PB in the ascending colon (AC) and descending colon (DC) but higher for BB only in the transverse colon (TC). This research illustrates the crucial role of meat analog physical structure in modulating nutritional aspects beyond food composition alone.