AKK bacteria affects colitis by regulating ferroptosis signaling pathway

To investigate whether Akkermansia muciniphila (AKK) bacteria affects colitis by regulating the ferroptosis signaling pathway, an mouse model of colitis was constructed, and the mice were administered with AKK and the ferroptosis agonist Erastin. HE staining and transmission electron microscopy were used to observe the pathological and microstructural changes of mouse colon tissues. The number of goblet cells was examined using alcian blue staining. The expression levels of oxidative stress-related indicators and ferroptosis-related proteins were detected by ELISA, western blot and immunohistochemisty analyses. Transcriptome and non-targeted metabolome sequencing were carried out to screen for differentially expressed genes and metabolites. Immunofluorescence double staining was used to detect the co-localization of cell adhesion-related indicators.16S microbiota sequencing was performed on mouse feces. Erastin caused damage to colon tissues, decreased the expression of ZO-1 and E-Cadherin, and increased the expression of oxidative stress and ferroptosis-related indicators. The species-abundance was increased after AKK treatment, while it was decreased after treatment with AKK bacteria+Erastin. AKK alleviated inflammatory cell infiltration, reduced organelle damage, and decreased the number of goblet cells in mice with colitis. MDA, ROS, and Fe2+ levels in colitis tissues were increased, but they were decreased after AKK bacteria treatment. The expression of GPX4 and SLC7A11 was decreased, while ACSL4 was increased. After intervention with AKK bacteria, the trend of changes in the above indicators was reversed, and 19 differential pathways were enriched. In conclusion, AKK bacteria can treat colitis in mice, and its mechanism may be related to regulating the ferroptosis signaling pathway. Overall design: To investigate whether Akkermansia muciniphila (AKK) bacteria affects colitis by regulating the ferroptosis signaling pathway, an mouse model of colitis was constructed, and the mice were administered with AKK and the ferroptosis agonist Erastin. Transcriptome sequencing were carried out to screen for differentially expressed genes.Sample group "Control" refers to: The SPF grade C57BL/6J mice (male, 6 weeks old) were kept in an environment with a temperature of 20-26? and a humidity of 40-70%, and have free access to food and water. Sample group "Model" refers to: To construct the colitis model, the mice were given 3% DSS solution for free drinking for one week, followed by DAI scoring and HE validation. During the intervention period, the model group was administered with equal volumes of PBS by gavage.Sample group "AKK" refers to:During the intervention period, the AKK group was administered with AKK bacteria. The bacterial solution concentration was 1.5 x109 CFU/mL, and the gavage volume was 0.1 mL/animal, once a week for 6 weeks.