Biosynthesis of polyamine-polyphosphate granules for colitis alleviation.

Natural polyamines, such as spermidine and spermine, exert strong anti-inflammatory effects, but their therapeutic benefits are limited by rapid absorption in the small intestine, resulting in low colonic availability. In this study, engineered Citrobacter freundii overexpressing ppk1 (CPP) could significantly enhance both intracellular polyamine synthesis and polyphosphates (PolyP) accumulation. Under a two-step cultivation process, the engineered strain produced substantial amounts of polyamines, including spermidine (145.14 ± 5.11 mg/g) and spermine (175.31 ± 4.2 mg/g). CPP responds to environmental stress by importing large amounts of phosphate for PolyP synthesis. This process further promotes polyamine production, which binds to PolyP to neutralize intracellular charge. The resulting polyamine-polyphosphate granules (PPGs) enhance both binding stability and slow-release properties in vivo. Notably, the oral administration of PPGs increased colonic polyamine levels, alleviated DSS-induced colitis, reduced inflammatory cytokines, and restored gut microbiota balance. Overall, biosynthesized PPGs represent a highly promising material for mitigating colitis.