NLRP6 Protects Il10 Mice from Colitis by Limiting Colonization of Akkermansia muciniphila

Seregin, Sergey S.; Golovchenko, N.; Schaf, Bryan; Chen, Jiachen; Pudlo, Nicholas A.; Mitchell, Jonathan; Baxter, Nielson T.; Zhao, Lili; Schloss, Patrick D.; Martens, Eric C.; Eaton, Kathryn A.; Chen, Grace Y.

doi:10.1016/j.celrep.2017.05.074

Cited by 80 publications

(52 citation statements)

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“…In addition, NLRP6-induced IL-18 cytokine expression prevents colitis in Il-10 -/- mice by limiting expansion of Akkermansia muciniphila (22**). A. muciniphila induces colitis in specific-pathogen-free (SPF) Il-10 -/- mice, likely owing to its ability to degrade mucus and activate TLR4/MYD88 signaling (22**). Similarly, Chen et al demonstrated that NLRP12, whose expression is downregulated in UC patients, prevents microbiota-driven colitis (23*).…”

Section: Innate Sensors and Immune Signalingmentioning

confidence: 99%

Novel insights into microbiome in colitis and colorectal cancer

Yang¹,

Jobin

2017

Current Opinion in Gastroenterology

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Purpose of review Microbiota is a major component of the etiology of inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Here, we summarize key advances achieved the past 18 months (ending June 2017) toward a better understanding of the role of microbiota in colitis and CRC development. Recent findings Accumulating evidence shows the essential role of intestinal barrier function (e.g., mucus, IgA, LCN2, LYPD8) in protecting against bacteria-induced inflammation and tumor development. Numerous signaling pathways (e.g., TLRs, NLRs), metabolites (e.g., indole, bile acids, retinoic acid) and small non-coding RNAs (e.g., miRNA) have been identified as key mediators regulating host-microbe interactions in the intestine. Novel microbial drivers of colitis and tumorigenesis (e.g., Alistipes finegoldii, Atopobium parvalum, Peptostreptococcus anaerobius) have been identified and their disease-promoting activities have been described. Summary IBD-associated colorectal cancer results from a complex breakdown of communication between the host and its microbiota, involving barrier function, immune signaling and metabolites.

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Section: Innate Sensors and Immune Signalingmentioning

confidence: 99%

Novel insights into microbiome in colitis and colorectal cancer

Yang¹,

Jobin

2017

Current Opinion in Gastroenterology

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“…Surprisingly, the authors demonstrate that co‐housing does not equilibrate Akkermansia colonization and colitis susceptibility. This study identified level of Akkermansia colonization as the critical determinant of colitis susceptibility in Il10 −/− mice and shows that the abundance of Akkermansia is actively regulated by NLRP6‐IL‐18 axis …”

Section: Inflammasomes In Intestinal Pathologies: Implications For Pymentioning

confidence: 78%

“…133 Another study suggests that NLRP6 restricts abundance of mucin-degrading microbe, Akkermansia muciniphila through IL-18 production and thereby reduces spontaneous colitis in Il10 −/− mice. 134 Surprisingly, the authors demonstrate that co-housing does not equilibrate Akkermansia colonization and colitis susceptibility. This study identified level of Akkermansia colonization as the critical determinant of colitis susceptibility in Il10 −/− mice and shows that the abundance of Akkermansia is actively regulated by NLRP6-IL-18 axis.…”

Section: Nlrp6mentioning

confidence: 96%

“…Decreased IL‐18 production due to abrogated NLRP6 activation leads to an altered AMP landscape that further promotes microbial dysbiosis and colitogenic response . Another study suggests that NLRP6 restricts abundance of mucin‐degrading microbe, Akkermansia muciniphila through IL‐18 production and thereby reduces spontaneous colitis in Il10 −/− mice . Surprisingly, the authors demonstrate that co‐housing does not equilibrate Akkermansia colonization and colitis susceptibility.…”

Section: Inflammasomes In Intestinal Pathologies: Implications For Pymentioning

confidence: 97%

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Inflammatory cell death in intestinal pathologies

Sharma

Kanneganti

2017

Immunological Reviews

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Summary The intestinal tract is a site of intense immune cell activity that is poised to mount an effective response against a pathogen and yet maintain tolerance towards commensal bacteria and innocuous dietary antigens. The role of cell death in gut pathologies is particularly important as the intestinal epithelium undergoes self-renewal every four to seven days through a continuous process of cell death and cell division. Cell death is also required for removal of infected, damaged and cancerous cells. Certain forms of cell death trigger inflammation through release of damage associated molecular patterns (DAMPs). Further, molecules involved in cell-death decisions also moonlight as critical nodes in immune signaling. The manner of cell death is, therefore, highly instructive of the immunological consequences that ensue. Perturbations in cell death pathways can impact the regulation of the immune system with deleterious consequences. In this review, we discuss the various forms of cell death with a special emphasis on lytic cell death pathways of pyroptosis and necroptosis and their implications in inflammation and cancer in the gut. Understanding the implications of distinct cell death pathways will help in the development of therapeutic interventions in intestinal pathologies.

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“…These mice have been shown to harbor a dysbiotic microbiome [82] at some vivaria, which contributes to modelsof autoinflammation [82] and cardiometabolic disease. [72,[84][85][86][87][88] Moreover, the dysbiotic microbiome in NLRP6deficient mice features an inherent dominance over the indigenous wild-type (WT) gut microbiome as, upon transfer, it takes over the niche and transmits disease susceptibility into recipient WT mice. [72,[84][85][86][87][88] Moreover, the dysbiotic microbiome in NLRP6deficient mice features an inherent dominance over the indigenous wild-type (WT) gut microbiome as, upon transfer, it takes over the niche and transmits disease susceptibility into recipient WT mice.…”

Section: Altered Homeostasis May Elicit Antagonistic Gut-microbe-hostmentioning

confidence: 99%

When Cultures Meet: The Landscape of “Social” Interactions between the Host and Its Indigenous Microbes

2019

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Animals exist as biodiverse composite organisms that include microbial residents, eukaryotic cells, and organs that collectively form a human being. Through an interdependent relationship and an inherent ability to transmit and reciprocate stimuli in a bidirectional way, a human body or the holobiont secures growth, health, and reproduction. As such, the survival of a holobiont is dependent on the maintenance of biological order including metabolic homeostasis by tight regulation of the communication between its eukaryotic and prokaryotic residents. In this review an overview and perspective are provided on the bidirectional communication between microbes and their host in mutually nurturing biochemical, biological, and social interconnected relationships between the components of the holobiont. An emphasis is placed on exemplifying microbiome-mediated effects on host functions-aiming to integrate microbiome functionality to host physiology, be it health or disease. Nutrition, immunology, and sexual dimorphism have been traversed extensively to reflect on health and mind states, social interactions, and urbanization defects/effects. Finally, examples of molecular mechanisms potentially orchestrating these complex transkingdom interactions are provided. We Nurture an Intricate Relationship with Our Symbiotic MicrobesHumans and their indigenous microbiomes are uniquely symbiotic in a number of facets. Indeed, many human genes are homologous to bacterial genes that are predominant in

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NLRP6 Protects Il10 Mice from Colitis by Limiting Colonization of Akkermansia muciniphila

Cited by 80 publications

References 0 publications

Novel insights into microbiome in colitis and colorectal cancer

Novel insights into microbiome in colitis and colorectal cancer

Inflammatory cell death in intestinal pathologies

When Cultures Meet: The Landscape of “Social” Interactions between the Host and Its Indigenous Microbes

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