Abstract
Effective oral interventions for alcohol-induced metabolic stress and liver injury remain limited. Pre-absorptive gastrointestinal alcohol handling is gaining interest as a non-pharmacological strategy to reduce hepatic burden. In this study, we developed a formulation-integrated, food-compatible lyophilized recombinant whole-cell catalyst based on Escherichia coli Nissle 1917 engineered to express alcohol dehydrogenase and acetaldehyde dehydrogenase. Rather than focusing exclusively on strain-level genetic modification, the engineered cells were protected by lyophilization combined with a food-grade chitosan–alginate layer-by-layer coating, forming an artificial cell wall designed to enhance survivability during oral delivery. The formulation resisted simulated gastric acid, sodium taurocholate, and ethanol, retained enzymatic activity after storage, and demonstrated formulation stability. In alcohol-exposed mice, oral administration reduced blood ethanol and acetaldehyde levels, improved liver biochemical parameters, attenuated hepatic steatosis, and partially restored oxidative stress indicators. Integrated multi-omics analyses indicated coordinated gut-associated metabolic and inflammatory responses to alcohol and intervention, rather than a single dominant pathway. These findings provide hypothesis-generating evidence; causality remains to be established. Overall, this study demonstrates a proof-of-concept, food-compatible lyophilized recombinant whole-cell catalyst that integrates enzymatic function with formulation stability and gastrointestinal resilience, highlighting an applied, food-compatible microbial framework for exploring alcohol-related metabolic stress.