Modification of chestnut starch with amylosucrase from Deinococcus geothermalis (DGAS) increases the proportion of resistant starch. DGAS-modified chestnut starch (DMCS) attenuates obesity in diet-induced obese mice via a receptor of short chain fatty acids (SCFAs), G-protein-coupled receptor 43. SCFAs are gut microbial metabolites produced by fermenting resistant starch and have key roles in the obesity-ameliorating effects of DMCS. Here, we evaluated the mechanical links among DMCS-induced changes in the gut microbiota, consequent production of microbial metabolites, and host genetic responses. Supplementation with DMCS altered the proportions of cecal microbiota, such as Ruminococcaceae and Bacteroides; microbial metabolites, such as acetic acid; and some carbohydrate metabolites. DMCS also induced changes in the expression of some genes in cecal epithelial cells, including genes involved in energy production, the cell cycle, and cellular junctions. Changes in the gut microbiota, microbial metabolites, and host gene expression were found to be significantly correlated. Our findings demonstrated the integrated and incorporated association among the gut microbiota, their beneficial metabolites, and the host transcriptome, which contributed to clarifying the anti-obesity effects of DMCS as a prebiotic. Therefore, fortifying resistant starch by modification of chestnut starch using DGAS may be a good strategy in the functional food industry.