Inactivated Akkermansia muciniphila AKK PROBIO Preserves Intestinal Homeostasis and Ameliorates DSS-Induced Colitis in Mice

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease with escalating global incidence. Conventional therapies face limitations including substantial costs and adverse effects, while live probiotics pose safety risks in vulnerable populations. Postbiotics-inactivated microorganisms conferring health benefits-offer therapeutic potential without viable bacterial risks. This study investigated inactivated <i>Akkermansia muciniphila</i> AKK PROBIO in dextran sulfate sodium (DSS)-induced colitis mice. Inactivated AKK PROBIO significantly ameliorated disease manifestations, restoring body weight and food intake during days 10-14 (<i>p</i> < 0.01) and reducing Disease Activity Index scores (<i>p</i> < 0.0001). Treatment preserved colonic architecture, enhanced tight junction proteins (Claudin-1, Occludin, ZO-1), and elevated mucin 2 expression. Mechanistically, AKK PROBIO modulated inflammatory responses by increasing anti-inflammatory interleukin-10 (<i>p</i> < 0.05) while decreasing pro-inflammatory cytokines IL-1β, IL-6, and TNF-α (all <i>p</i> < 0.05). 16S rRNA sequencing revealed selective microbiota remodeling with enriched beneficial genera (<i>Ligilactobacillus</i>, <i>Lachnospiraceae_NK4A136_group</i>, <i>Bacteroides</i>, <i>Akkermansia</i>) and depleted pathobionts (<i>Escherichia-Shigella</i>). Functional profiling demonstrated enhanced microbial metabolic capacity in carbohydrate and amino acid metabolism pathways. Gas chromatography-mass spectrometry analysis confirmed elevated short-chain fatty acid production, particularly butyrate and isocaproate (<i>p</i> < 0.05). Correlation analyses revealed interconnected relationships among beneficial microbiota, short-chain fatty acids, and anti-inflammatory mediators, while showing inverse associations with pro-inflammatory cytokines. In summary, our findings demonstrate that inactivated AKK PROBIO alleviates colitis, supporting its development as a safe, food-derived postbiotic.