The Digestive Symphony: Orchestrating Host-Microbiome Enzyme Interactions in the Gut Ecosystem

Digestion was once considered a host-driven process, relying on salivary, gastric, pancreatic, and intestinal enzymes to break down macronutrients. However, new insights into the gut flora have redefined this view, emphasizing that digestion is the result of synergistic action between host and microbial enzymes. Host enzymes initiate nutrient breakdown, while microbial enzymes (especially in the colon) extend this process by fermenting resistant polysaccharides, modifying bile acids, and converting phytochemicals and xenobiotics into bioactive compounds. These microbial actions produce metabolites like short-chain fatty acids, which in turn affect gut barrier function, immune regulation, and metabolism.

Two frameworks describe this interaction: "Duet," emphasizing sequential enzymatic collaboration; and "Orchestra," reflecting a spatially and temporally coordinated system with host-microbiome feedback. This symbiotic relationship, when disrupted by antibiotics, inflammation, diet, or aging, leads to dysbiosis, impaired digestive function, and metabolic, neurological, cardiovascular, and inflammatory diseases. Recognizing digestion as a dynamic, integrated system opens new avenues for therapy and nutrition. These avenues include enzyme-targeted prebiotics, probiotics, postbiotics, and personalized diets. This systems-level perspective helps innovate diagnostics and treatments aimed at restoring enzymatic balance and improving digestive and systemic health.