Cyanobacteria–probiotics symbionts for modulation of intestinal inflammation and microbiome dysregulation in colitis

Inflammatory bowel disease (IBD) is often associated with excessive inflammatory response and highly dysregulated gut microbiota. Traditional treatments utilize drugs to manage inflammation, potentially with probiotic therapy as an adjuvant. However, current standard practices often suffer from detrimental side effects, low bioavailability, and unsatisfactory therapeutic outcomes. Microbial complexes characterized by mutually beneficial symbiosis hold great promise for IBD therapy. Here, we aggregated <i>Synechocystis</i> sp. PCC6803 (Sp) with <i>Bacillus subtilis</i> (BS) by biomimetic mineralization to form cyanobacteria-probiotics symbionts (ASp@BS), which reshaped a healthy immune system and gut microbiota in a murine model of acute colitis. The symbionts exhibited excellent tolerance to the harsh environment of the gastrointestinal tract. Importantly, probiotics within the symbionts created a local anaerobic environment to activate the [NiFe]-hydrogenase enzyme of cyanobacteria, facilitating the production of hydrogen gas (H₂) to persistently scavenge elevated reactive oxygen species and alleviate inflammatory factors. The resulting reduced inflammation improves the viability of the probiotics to efficiently regulate the gut microbiota and reshape the intestinal barrier functions. Our research elucidates that ASp@BS leverages the synergistic interaction between Sp and BS to create a therapeutic platform that addresses multiple aspects of IBD, offering a promising and comprehensive solution for IBD treatment.