Alleviation of Ulcerative Colitis in Mice by Individual Fermentation of Periplaneta americana Powder with L. bulgaricus SN22 and S. thermophilus SN05

The escalating global incidence of ulcerative colitis (UC) underscores the demand for novel therapeutic strategies. This study investigated the fermentation of <i>Periplaneta americana</i> (PA) powder using two conventional dairy starter strains, <i>Lactobacillus delbrueckii</i> subsp. <i>bulgaricus</i> SN22 and <i>Streptococcus thermophilus</i> SN05, to enhance its functional properties, particularly anti-inflammatory activity, via microbial processing. Both strains demonstrated favourable safety and antimicrobial activity. Untargeted metabolomics revealed that fermentation significantly altered the metabolite profile of the PA supernatant, enriching compounds with potential bioactivities, notably anti-inflammatory (e.g., 3-anisic acid) and antioxidant (e.g., vitamin U) properties. In the DSS-induced mouse colitis model, treatment with the fermented supernatant alleviated intestinal inflammation compared to the unfermented group. This was demonstrated by significantly reduced levels of the pro-inflammatory cytokines IL-1β and TNF-α, along with improved maintenance of intestinal barrier integrity. Further in vitro assays showed that the fermented supernatant significantly suppressed proliferation and clonogenicity in human HT-29 colon cancer cells, while also inducing reactive oxygen species accumulation and apoptosis. Results demonstrate these strains are multifunctional starters possessing superior antimicrobial and anti-inflammatory efficacy. This study employed LAB fermentation of insect-derived matrices to derive bioactive components. The fermentation products exhibited anti-inflammatory potential, offering a potential microbial transformation strategy for developing functional products for adjunctive UC intervention.