Browsing by Subject "ENTEROCYTES"

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  • van der Lugt, Benthe; van Beek, Adriaan A.; Aalvink, Steven; Meijer, Ben; Sovran, Bruno; Vermeij, Wilbert P.; Brandt, Renata M. C.; de Vos, Willem M.; Savelkoul, Huub F. J.; Steegenga, Wilma T.; Belzer, Clara (2019)
    BackgroundThe use of Akkermansia muciniphila as potential therapeutic intervention is receiving increasing attention. Health benefits attributed to this bacterium include an improvement of metabolic disorders and exerting anti-inflammatory effects. The abundance of A. muciniphila is associated with a healthy gut in early mid- and later life. However, the effects of A. muciniphila on a decline in intestinal health during the aging process are not investigated yet. We supplemented accelerated aging Ercc1(-/7) mice with A. muciniphila for 10weeks and investigated histological, transcriptional and immunological aspects of intestinal health.ResultsThe thickness of the colonic mucus layer increased about 3-fold after long-term A. muciniphila supplementation and was even significantly thicker compared to mice supplemented with Lactobacillus plantarum WCFS1. Colonic gene expression profiles pointed towards a decreased expression of genes and pathways related to inflammation and immune function, and suggested a decreased presence of B cells in colon. Total B cell frequencies in spleen and mesenteric lymph nodes were not altered after A. muciniphila supplementation. Mature and immature B cell frequencies in bone marrow were increased, whereas B cell precursors were unaffected. These findings implicate that B cell migration rather than production was affected by A. muciniphila supplementation. Gene expression profiles in ileum pointed toward a decrease in metabolic- and immune-related processes and antimicrobial peptide production after A. muciniphila supplementation. Besides, A. muciniphila decreased the frequency of activated CD80(+)CD273(-) B cells in Peyer's patches. Additionally, the increased numbers of peritoneal resident macrophages and a decrease in Ly6C(int) monocyte frequencies in spleen and mesenteric lymph nodes add evidence for the potentially anti-inflammatory properties of A. muciniphila.ConclusionsAltogether, we show that supplementation with A. muciniphila prevented the age-related decline in thickness of the colonic mucus layer and attenuated inflammation and immune-related processes at old age. This study implies that A. muciniphila supplementation can contribute to a promotion of healthy aging.
  • Ottman, Noora; Reunanen, Justus; Meijerink, Marjolein; Pietilä, Taija; Kainulainen, Veera; Klievink, Judith; Huuskonen, Laura; Aalvink, Steven; Skurnik, Mikael; Boeren, Sjef; Satokari, Reetta; Mercenier, Annick; Palva, Airi; Smidt, Hauke; de Vos, Willem M.; Belzer, Clara (2017)
    Gut barrier function is key in maintaining a balanced response between the host and its microbiome. The microbiota can modulate changes in gut barrier as well as metabolic and inflammatory responses. This highly complex system involves numerous microbiota-derived factors. The gut symbiont Akkermansia muciniphila is positively correlated with a lean phenotype, reduced body weight gain, amelioration of metabolic responses and restoration of gut barrier function by modulation of mucus layer thickness. However, the molecular mechanisms behind its metabolic and immunological regulatory properties are unexplored. Herein, we identify a highly abundant outer membrane pili-like protein of A. muciniphila MucT that is directly involved in immune regulation and enhancement of trans-epithelial resistance. The purified Amuc_1100 protein and enrichments containing all its associated proteins induced production of specific cytokines through activation of Toll-like receptor (TLR) 2 and TLR4. This mainly leads to high levels of IL-10 similar to those induced by the other beneficial immune suppressive microorganisms such as Faecalibacterium prausnitzii A2-165 and Lactobacillus plantarum WCFS1. Together these results indicate that outer membrane protein composition and particularly the newly identified highly abundant pili-like protein Amuc_1100 of A. muciniphila are involved in host immunological homeostasis at the gut mucosa, and improvement of gut barrier function.