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Intestinal Akkermansia muciniphila predicts clinical response to PD1 blockade in advanced non-small cell lung cancer patients [RNA-seq].

ABSTRACT: The endpoint of this study was to prospectively validate the prognostic significance of fecal Akk in advanced NSCLC patients treated with first or second line ICI. We performed RNA sequencing to compare transcriptomic profiles of the different groups.

ORGANISM(S): Homo sapiens

PROVIDER: GSE182328 | GEO | 2021/08/20

REPOSITORIES: GEO

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Akkermansia muciniphila blunts Th17 cells

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.

2023-01-01 | GSE211578 | GEO

Intestinal Akkermansia muciniphila predicts clinical response to PD1 blockade in advanced non-small cell lung cancer patients [RNA-seq].

Project description:Intestinal Akkermansia muciniphila predicts clinical response to PD1 blockade in advanced non-small cell lung cancer patients [RNA-seq].

| PRJNA755863 | ENA

Akkermansia muciniphila blunts Th17 cells [Colonic lymphocytes]

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.

2022-12-31 | GSE214253 | GEO

Akkermansia muciniphila phospholipid induces homeostatic immune responses.

Project description:Multiple studies have established associations between human gut bacteria and host physiology, but determining the molecular mechanisms underlying these associations has been challenging1-3. Akkermansia muciniphila has been robustly associated with positive systemic effects on host metabolism, favourable outcomes to checkpoint blockade in cancer immunotherapy and homeostatic immunity4-7. Here we report the identification of a lipid from A. muciniphila's cell membrane that recapitulates the immunomodulatory activity of A. muciniphila in cell-based assays8. The isolated immunogen, a diacyl phosphatidylethanolamine with two branched chains (a15:0-i15:0 PE), was characterized through both spectroscopic analysis and chemical synthesis. The immunogenic activity of a15:0-i15:0 PE has a highly restricted structure-activity relationship, and its immune signalling requires an unexpected toll-like receptor TLR2-TLR1 heterodimer9,10. Certain features of the phospholipid's activity are worth noting: it is significantly less potent than known natural and synthetic TLR2 agonists; it preferentially induces some inflammatory cytokines but not others; and, at low doses (1% of EC50) it resets activation thresholds and responses for immune signalling. Identifying both the molecule and an equipotent synthetic analogue, its non-canonical TLR2-TLR1 signalling pathway, its immunomodulatory selectivity and its low-dose immunoregulatory effects provide a molecular mechanism for a model of A. muciniphila's ability to set immunological tone and its varied roles in health and disease.

| S-EPMC9328018 | biostudies-literature

Diet-driven differential response of Akkermansia muciniphila modulates pathogen susceptibility

Project description:The erosion of the colonic mucus layer by a dietary fiber-deprived gut microbiota results in heightened susceptibility to an attaching and effacing pathogen, Citrobacter rodentium. Nevertheless, the questions of whether and how specific mucolytic bacteria aid in the increased pathogen susceptibility remain unexplored. Here, we leverage a functionally characterized, 14-member synthetic human microbiota in gnotobiotic mice to deduce which bacteria and functions are responsible for the pathogen susceptibility. Using strain dropouts of mucolytic bacteria from the community, we show that Akkermansia muciniphila renders the host more vulnerable to the mucosal pathogen during fiber deprivation. However, the presence of A. muciniphila reduces pathogen load on a fiber-sufficient diet, highlighting the context-dependent beneficial effects of this mucin specialist. The enhanced pathogen susceptibility is not owing to altered host immune or pathogen responses, but is driven by a combination of increased mucus penetrability and altered activities of A. muciniphila and other community members. Our study provides novel insights into the mechanisms of how discrete functional responses of the same mucolytic bacterium either resist or enhance enteric pathogen susceptibility.

| S-SCDT-10_1038-S44320-024-00036-7 | biostudies-other

Crystal structure of monomeric Amuc_1100 from Akkermansia muciniphila.

Project description:Many human diseases, such as obesity and diabetes, show annual increases in prevalence and often involve intestinal microbes. One such probiotic bacterium, Akkermansia muciniphila, which was discovered a decade ago, has been reported to influence glucose homeostasis and to contribute to gut health. Amuc_1100, a functionally uncharacterized protein of A. muciniphila, was found to be a key active component in reducing the body weight of mice. Here, the crystal structure of Amuc_1100 (residues 31-317), referred to as Amuc_1100*, is reported at 2.1 Å resolution. Amuc_1100* has a similar fold to three proteins related to pilus formation, PilO, PilN and EpsL, indicating a similar function. Biochemical investigations further confirmed a monomeric state for the soluble region of Amuc_1100, which differs from the dimeric states of PilO, PilN and EpsL. This study provides a structural basis for the elucidation of the molecular mechanism of Amuc_1100.

| S-EPMC7137384 | biostudies-literature

Study of growth, metabolism, and morphology of Akkermansia muciniphila with an in vitro advanced bionic intestinal reactor.

Project description:BackgroundAs a kind of potential probiotic, Akkermansia muciniphila abundance in human body is directly causally related to obesity, diabetes, inflammation and abnormal metabolism. In this study, A. muciniphila dynamic cultures using five different media were implemented in an in vitro bionic intestinal reactor for the first time instead of the traditional static culture using brain heart infusion broth (BHI) or BHI + porcine mucin (BPM).ResultsThe biomass under dynamic culture using BPM reached 1.92 g/L, which improved 44.36% compared with the value under static culture using BPM. The biomass under dynamic culture using human mucin (HM) further increased to the highest level of 2.89 g/L. Under dynamic culture using porcine mucin (PM) and HM, the main metabolites were short-chain fatty acids (acetic acid and butyric acid), while using other media, a considerable amount of branched-chain fatty acids (isobutyric and isovaleric acids) were produced. Under dynamic culture Using HM, the cell diameters reached 999 nm, and the outer membrane protein concentration reached the highest level of 26.26 μg/mg.ConclusionsThis study provided a preliminary theoretical basis for the development of A. muciniphila as the next generation probiotic.

| S-EPMC7901181 | biostudies-literature

Akkermansia muciniphila

Project description:Akkermansia muciniphila Genome sequencing

| PRJNA1145077 | ENA

Akkermansia muciniphila

Project description:Akkermansia muciniphila Raw sequence reads

| PRJNA1112731 | ENA

Akkermansia muciniphila

Project description:Akkermansia muciniphila Genome sequencing and assembly

| PRJNA774135 | ENA