Short-chain fatty acids (SCFAs), as key metabolites produced by the intestinal microbiota from the fermentation of dietary fiber and other substrates, play a crucial role in maintaining intestinal barrier function, regulating immune balance, and promoting systemic health. This review explores strategies for utilizing engineered food microorganisms (particularly probiotics) as novel “bio-factories” to achieve efficient and precise synthesis of SCFAs. This review outlines the core selection criteria for ideal engineered chassis strains, including their safety for application, robustness in the intestinal environment, and genetic tractability. It then details strategies for significantly enhancing the efficiency of SCFA synthesis in food microorganisms such as discovery and engineering of rate-limiting enzymes, intelligent enzyme engineering modifications, and artificial intelligence-driven metabolic network optimization. Furthermore, this review discusses how to integrate biosensors and clustered regularly interspaced short palindromic repeats-based dynamic regulation systems to achieve on-demand and precise modulation of SCFAs within the intestinal microecology. The application prospects of engineered food microorganisms are discussed in two major directions: First, in vitro food industrial biomanufacturing, i.e., utilizing engineered strains to efficiently produce SCFAs in fermentation systems as food ingredients or additives; this pathway exhibits relatively high technical maturity and a relatively clear regulatory framework. Second, in vivo live biotherapeutics, i.e., direct ingestion of engineered probiotics to in situ synthesize SCFAs in the gut. This pathway holds significant potential for personalized nutritional intervention and gut health management, but faces greater challenges in safety assessment and regulation.

Milk allergy is one of the most common food allergies, affecting 6% of young children, and β-lactoglobulin (β-LG) is the main milk allergen. Clostridium tyrobutyricum Z816 was selected for the degradation of β-LG, which was successfully reduced by about 90% using permeabilized bacteria under the optimized conditions. The hydrolyzed peptides were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and analyzed by molecular modeling, which indicated that C. tyrobutyricum Z816 could effectively degrade the antigenic epitopes of β-LG. Finally, the concentration and digestibility of β-LG in actual samples was quantified using enzyme-linked immunosorbent assay (ELISA) and gastrointestinal digestion simulation experiments. The results showed more than 92% of β-LG in actual samples was hydrolyzed, and the gastric and total digestibility of whey protein isolate (WPI) was improved by 85.96% and 64.51%, respectively. Therefore, C. tyrobutyricum Z816 offers an effective method to degrade β-LG and reduce the occurrence of milk allergies, which has great significance for the development of hypoallergenic dairy products.