Modulation of Mucosal Immune Response, Tolerance, and Proliferation in Mice Colonized by the Mucin-Degrader Akkermansia muciniphila
Muriel Derrien,Peter van Baarlen,Guido J. E. J. Hooiveld,Elisabeth Norin,Michael Müller,Willem M. de Vos,Willem M. de Vos +6 more
TLDR
It is proposed that A. muciniphila modulates pathways involved in establishing homeostasis for basal metabolism and immune tolerance toward commensal microbiota, and altered mucosal gene expression profiles toward increased expression of genes involved in immune responses and cell fate determination.Abstract:
Epithelial cells of the mammalian intestine are covered with a mucus layer that prevents direct contact with intestinal microbes but also constitutes a substrate for mucus-degrading bacteria. To study the effect of mucus degradation on the host response, germ-free mice were colonized with Akkermansia muciniphila. This anaerobic bacterium belonging to the Verrucomicrobia is specialized in the degradation of mucin, the glycoprotein present in mucus, and found in high numbers in the intestinal tract of human and other mammalian species. Efficient colonization of A. muciniphila was observed with highest numbers in the cecum, where most mucin is produced. In contrast, following colonization by Lactobacillus plantarum, a facultative anaerobe belonging to the Firmicutes that ferments carbohydrates, similar cell-numbers were found at all intestinal sites. Whereas A. muciniphila was located closely associated with the intestinal cells, L. plantarum was exclusively found in the lumen. The global transcriptional host response was determined in intestinal biopsies and revealed a consistent, site-specific, and unique modulation of about 750 genes in mice colonized by A. muciniphila and over 1500 genes after colonization by L. plantarum. Pathway reconstructions showed that colonization by A. muciniphila altered mucosal gene expression profiles toward increased expression of genes involved in immune responses and cell fate determination, while colonization by L. plantarum led to up-regulation of lipid metabolism. These indicate that the colonizers induce host responses that are specific per intestinal location. In conclusion, we propose that A. muciniphila modulates pathways involved in establishing homeostasis for basal metabolism and immune tolerance toward commensal microbiota.read more
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Phylogenetic Analysis of Dysbiosis in Ulcerative Colitis During Remission
Mirjana Rajilić-Stojanović,Mirjana Rajilić-Stojanović,Fergus Shanahan,Francisco Guarner,Willem M. de Vos +4 more
TL;DR: Dysbiosis in UC is stable in time and shared between patients from different geographic locations, and the microbial alterations offer a mechanistic insight into the pathogenesis of the disease.
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Brandi L. Cantarel,Emmanuelle Waubant,Christel Chehoud,Justin Kuczynski,Todd Z. DeSantis,Janet Warrington,Arun Venkatesan,Claire M. Fraser,Ellen M. Mowry +8 more
TL;DR: Compared with the other groups, untreated patients with multiple sclerosis had an increase in the Akkermansia, Faecalibacterium, and Coprococcus genera after vitamin D supplementation.
Journal ArticleDOI
Pili-like proteins of Akkermansia muciniphila modulate host immune responses and gut barrier function
Noora Ottman,Noora Ottman,Noora Ottman,Justus Reunanen,Marjolein Meijerink,Taija E. Pietilä,Veera Kainulainen,Judith Klievink,Laura Huuskonen,Steven Aalvink,Mikael Skurnik,Mikael Skurnik,Sjef Boeren,Reetta Satokari,Annick Mercenier,Airi Palva,Hauke Smidt,Willem M. de Vos,Willem M. de Vos,Clara Belzer +19 more
TL;DR: 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.
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Administration of Akkermansia muciniphila Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice.
Xiaoyuan Bian,Wenrui Wu,Liya Yang,Longxian Lv,Qing Wang,Yating Li,Jianzhong Ye,Daiqiong Fang,Jingjing Wu,Xianwan Jiang,Ding Shi,Lanjuan Li +11 more
TL;DR: It is found that A. muciniphila treatment could ameliorate mucosal inflammation either via microbe-host interactions, which protect the gut barrier function and reduce the levels of inflammatory cytokines, or by improving the microbial community.
Journal ArticleDOI
Genetic and environmental control of host-gut microbiota interactions
Elin Org,Brian W. Parks,Jong Wha J. Joo,Benjamin L. Emert,William A. Schwartzman,Eun Yong Kang,Margarete Mehrabian,Calvin Pan,Rob Knight,Robert P. Gunsalus,Thomas A. Drake,Eleazar Eskin,Aldons J. Lusis +12 more
TL;DR: It is concluded that, in a controlled environment, the genetic background accounts for a substantial fraction of abundance of most common microbiota, and loci controlling microbiota composition are mapped and prioritized.
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