Project description:Akkermansia muciniphila is recognized as a promising probiotic that improves the symptoms of a variety of diseases. However, the role and mechanism of A. muciniphila in regulating intestinal homeostasis remain to be explored. Here, we discovered that A. muciniphila was dramatically increased during colitis recovery, and its colonization greatly increased goblet cells to protect the intestinal barrier in mice. Amuc_0904, a previously uncharacterized A. muciniphila outer membrane protein, was identified to induce goblet cell differentiation.We want to find the receptors that 904 interacts with cells to explore the detailed mechanism.
Project description:DSS-induced colitis mice were treated with PBS, A. muciniphila secreting extracellular vesicles (SEV) via gavage every day. mice colon tissues from each of the indicated group (Ctrl, Colitis and SEV) in (b) were collected. Mice colon tissues were submitted for scRNA-seq.
Project description:Akkermansia muciniphila, a common member of the human gut microbiota, is considered to be a beneficial resident of the intestinal mucus layer. Surface-exposed molecules produced by this organism likely play important roles in colonization and communication with other microbes and the host, but the protein composition of the outer membrane has not been characterized thus far. Herein we identify A. muciniphila proteins after enrichment and fractionation of the outer membrane proteome of A. muciniphila.
2016-09-27 | PXD004400 | Pride
Project description:Intestinal epithelial transcription factor HNF4A protects against microbiota-dependent spontaneous colitis associated with expansion of Akkermansia muciniphila
Project description:We implemented transcriptomic analyses of blood and hippocampus of old mice treated with Akkermansia muciniphila Membrane Protein for 8 weeks.
Project description:Histone lysine lactylation (Klac) is a new posttranslational modification (PTM) that is installed by acetyltransferase to modulate specific immune responses1 and oncogenesis2,3. Akkermansia muciniphila (A. muciniphila) is a beneficial bacterium that blunts ulcerative colitis (UC) in a mouse model by secreting extracellular vesicles (SEVs)4. Although many histone sites are known to contain lysine lactylation, whether this modification is regulated to modulate specific biological functions by exogenous acetyltransferase or intestinal microbiota is not well understood. Here, we discovered that SEV from A. muciniphila, rather than A. muciniphila per se, has anti-Th17 (T helper 17) differentiation activity. We further screened the composition of SEV and found that Amuc_2172 is the key active component. As a GCN5-related acetyltransferase of A. muciniphila, Amuc_2172 is accessible to naïve T cells and functions as a lactylation transferase on Lys4 of histone H3. Accelerated histone H3 lactylation (H3Klac) on Lys4 competitively blocks trimethylation (H3Kme3) on Il17a loci in the process of Th17-cell differentiation. Additionally, intraperitoneal application of recombinant Amuc_2172 also inhibited Th17 and dextran sulfate sodium (DSS)-induced UC phenotypes in vivo; moreover, bioengineered Amuc_2172 showed improved colitis site delivery and higher Th17 inhibition potential compared to Amuc_2172 alone. Our study reveals not only a potential therapeutic strategy for treating colitis but also a model via which lysine lactylation is regulated by the intestinal microbiota, which may be broadly applicable to understand the crosstalk of bacteria and immunity.
Project description:DSS-induced colitis mice were treated with PBS, A. muciniphila secreting extracellular vesicles (SEV) via gavage every day. Mice lymphocytes of colon tissues from each of the indicated group (Colitis and SEV) in were collected. Then CD4+ T cells are isolated from lymphocytes. These cells were submitted for scRNA-seq.
