Addressing the escalating global burdens of inflammatory bowel disease and antimicrobial resistance demanded innovative food-based approaches to fortify gut health and suppress pathogens. We introduced a novel edible probiotic, Enterococcus faecalis HY0110, isolated from marine Thunnus thynnus. Through comprehensive in vitro, in vivo, and metabolomic analyses, we demonstrated its superior antibacterial effects compared to Lactobacillus rhamnosus GG, along with significantly enhanced antioxidant and free-radical scavenging capacities. Notably, elevated acetic acid production strongly correlated with its antimicrobial efficacy (R ≥ 0.999). HY0110 also exerted antiproliferative effects on HT-29 colorectal cancer cells by attenuating β-catenin and BCL-2 expression while upregulating pro-apoptotic markers P62 and c-PARP. In a DSS-induced colitis model, HY0110 alleviated inflammation, restored gut microbial homeostasis, and enhanced deterministic processes in community assembly dynamics. Furthermore, fermenting Periplaneta americana powder with HY0110 triggered extensive metabolic remodeling, notably a 668.73-fold rise in astragaloside A, plus increases in L-Leucyl-L-Alanine, S-lactoylglutathione, and 16,16-dimethyl prostaglandin A1. These shifts diminished harmful components and amplified essential amino acids and peptides to bolster immune modulation, redox balance, and anti-inflammatory responses. This work established a transformative paradigm for utilizing marine probiotics and novel entomological substrates in functional foods, presenting strategic pathways for precision nutrition and inflammatory disease management.

The escalating global incidence of ulcerative colitis (UC) underscores the demand for novel therapeutic strategies. This study investigated the fermentation of Periplaneta americana (PA) powder using two conventional dairy starter strains, Lactobacillus delbrueckii subsp. bulgaricus SN22 and Streptococcus thermophilus 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.