Abstract

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by dysbiosis and impaired Short-chain fatty acids (SCFAs) production, but traditionally, dietary fiber interventions lack precision in gut microbiota modulation. Herein, a concept for a new system was introduced: bioengineered strain-specific synbiotics that combine CRISPR-Cas9-modified Bifidobacterium longum strains with metabolically tailored prebiotics aimed at optimal soluble fiber fermentation for targeted IBS management. The probiotics were metabolically engineered to overexpress enzymes involved in butyrate synthesis, while prebiotics were chemically tailored so as not to undergo off-target fermentation, ensuring their preferential use by the bioengineered strains. A quorum-sensing feedback loop was used to dynamically adjust metabolic activity in response to microbial density, thereby sustaining SCFA production along the colon. Moreover, real-time microbiome monitoring via a metagenomics sequencing subsystem self-adjusted the synbiotic dosage to minimize symptom severity while preserving microbial diversity. The closed-loop architecture of this system dynamically phases out plain fiber supplementation when butyrate production reached therapeutic thresholds, thus enabling personalized modulation of gut ecology. Proof of concept testing in vitro achieved a 40% reduction in off-target fermentation of acetylated xylo-oligosaccharides compared to that of native substrates. The herein proposed approach has distinguished advantages over one-size-fits-all static treatments by providing active, precision control over microbial metabolism; traditional therapies have mostly proved ineffective. This study represented one step further in synbiotic design development, capable of transforming the current paradigm of IBS treatment using targeted microbiome modulation.

Key words: Irritable bowel syndrome, synbiotics, gut microbiota, soluble fiber, short-chain fatty acids, fermentation, systematic review.