Akkermansia muciniphila, one of the most promising next-generation probiotics, was reported to exhibit beneficial modulatory effects on the gut barrier. However, the strain-specific and underlying regulatory mechanism...Akkermansia muciniphila, one of the most promising next-generation probiotics, was reported to exhibit beneficial modulatory effects on the gut barrier. However, the strain-specific and underlying regulatory mechanisms of this species on gut barrier function were not well studied. Therefore, this study evaluated the protective effect of A. muciniphila strains on the intestinal barrier and investigated the mode of action and material basis of this modulatory effect. We first confirmed the strain-specific effects of A. muciniphila on intestinal barrier regulation and found that this phenomenon may be explained by the different abilities of strains to affect tight junction protein expression in enterocytes. Comparative genomic analysis proved that the ability of A. muciniphila to regulate the intestinal barrier was exerted in part by the functional genes(such as COG0438, COG0463, and COG2244)related to the synthesis of cellular surface proteins. The role of these surface proteins in intestinal barrier regulation was further verified by strain-comparative experiments in animal and cell models and surface protein removal trials. This study confirmed the different effects of A. muciniphila strains on gut barrier modulation and provided molecular and genetic targets for the screening of A. muciniphila strains with superior protection against gut barrier dysfunction.展开更多
AIM: To evaluate the in vitro immunomodulation capacity of various non-pathogenic yeast strains and to investigate the ability of some of these food grade yeasts to prevent experimental colitis in mice.METHODS: In vit...AIM: To evaluate the in vitro immunomodulation capacity of various non-pathogenic yeast strains and to investigate the ability of some of these food grade yeasts to prevent experimental colitis in mice.METHODS: In vitro immunomodulation was assessed by measuring cytokines [interleukin (IL)-12p70,IL-10,tumor necrosis factor and interferon γ] released by human peripheral blood mononuclear cells after 24 h stimulation with 6 live yeast strains (Saccharomyces ssp.) and with bacterial reference strains.A murine model of acute 2-4-6-trinitrobenzene sulfonic acid (TNBS)-colitis was next used to evaluate the distinct prophylactic protective capacities of three yeast strains compared with the performance of prednisolone treatment.RESULTS: The six yeast strains all showed similar non-discriminating anti-inflammatory potential when tested on immunocompetent cells in vitro .However,although they exhibited similar colonization patterns in vivo ,some yeast strains showed significant anti-inflammatory activities in the TNBS-induced colitis model,whereas others had weaker or no preventive effect at all,as evidenced by colitis markers (body-weight loss,macroscopic and histological scores,myeloperoxidase activities and blood inflammatory markers).CONCLUSION: A careful selection of strains is required among the biodiversity of yeasts for specific clinical studies,including applications in inflammatory bowel disease and other therapeutic uses.展开更多
基金supported by the Natural Science Foundation of Jiangsu Province (BK20200084)The National Natural Science Foundation of China (32021005 and 31871773)Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province。
文摘Akkermansia muciniphila, one of the most promising next-generation probiotics, was reported to exhibit beneficial modulatory effects on the gut barrier. However, the strain-specific and underlying regulatory mechanisms of this species on gut barrier function were not well studied. Therefore, this study evaluated the protective effect of A. muciniphila strains on the intestinal barrier and investigated the mode of action and material basis of this modulatory effect. We first confirmed the strain-specific effects of A. muciniphila on intestinal barrier regulation and found that this phenomenon may be explained by the different abilities of strains to affect tight junction protein expression in enterocytes. Comparative genomic analysis proved that the ability of A. muciniphila to regulate the intestinal barrier was exerted in part by the functional genes(such as COG0438, COG0463, and COG2244)related to the synthesis of cellular surface proteins. The role of these surface proteins in intestinal barrier regulation was further verified by strain-comparative experiments in animal and cell models and surface protein removal trials. This study confirmed the different effects of A. muciniphila strains on gut barrier modulation and provided molecular and genetic targets for the screening of A. muciniphila strains with superior protection against gut barrier dysfunction.
文摘AIM: To evaluate the in vitro immunomodulation capacity of various non-pathogenic yeast strains and to investigate the ability of some of these food grade yeasts to prevent experimental colitis in mice.METHODS: In vitro immunomodulation was assessed by measuring cytokines [interleukin (IL)-12p70,IL-10,tumor necrosis factor and interferon γ] released by human peripheral blood mononuclear cells after 24 h stimulation with 6 live yeast strains (Saccharomyces ssp.) and with bacterial reference strains.A murine model of acute 2-4-6-trinitrobenzene sulfonic acid (TNBS)-colitis was next used to evaluate the distinct prophylactic protective capacities of three yeast strains compared with the performance of prednisolone treatment.RESULTS: The six yeast strains all showed similar non-discriminating anti-inflammatory potential when tested on immunocompetent cells in vitro .However,although they exhibited similar colonization patterns in vivo ,some yeast strains showed significant anti-inflammatory activities in the TNBS-induced colitis model,whereas others had weaker or no preventive effect at all,as evidenced by colitis markers (body-weight loss,macroscopic and histological scores,myeloperoxidase activities and blood inflammatory markers).CONCLUSION: A careful selection of strains is required among the biodiversity of yeasts for specific clinical studies,including applications in inflammatory bowel disease and other therapeutic uses.