P9 protein from Akkermansia muciniphila stimulates L cells by binding to the IAM 2 receptor, leading to GLP-1 release.

“propionate gets converted to butyrate by another bacteria which ones there is a a class of um clal strains that will do that secondary conversion and Clum butterum is sort of the most well studied of those got it what about defil is he doing anything good for us there actually don't know we haven't studied whether and maybe people are afraid to bring that into the lab yeah yeah and what does P9 do and so P9 is directly stimulates L cells yes it binds to this IAM 2 receptor on the L cells and stimulates them IAM receptors are receptors that are usually involved in um God if my memory serves me correctly like kind of an immune response right like an inflammatory response well and that is uh you know for we we have not done studies around that but for sure that is a area of heavy interest um yeah by vague recollection I mean we're literally going back 25 years is that when you when a person is uh for example septic right you have all of these IAM modules that lead to you know Vaso dilation leaky capillaries secretion of monocytes out into the peripheral tissue as macroasia um sounds like this is a distinct process here yeah well I mean and and maybe I should say too like I don't know how much of this is tied to that process but the other thing that not not only does acran stimulate uh these L cells to produce gop1 but acran has another role which maybe is very much tied to this um you know which is that uh it it helps regulate the mucin layer and so that mucin layer turns out to be super important for uh if it gets too thin or if it's too thick it's it's it's a real this so-called leaky gut or GI issues that that become a result of not having enough acromania is really that you have too thin of a mucin layer and so you start to get um you know the ability for pathogens to infiltrate and then also obviously for these molecules to secrete out and then tell me what's the fate of the butyrate made of the propionate it binds to these G protein coupled receptors — and that's also what stimulates the L cells to then go release glp1 got it”

“and that surface protein by itself just stimulates L cells in the um in the osy and that we know that that makes glp one yeah”

“so you eat food if you provided you have a lot of acromania and you're feeding at the right food a couple things happen it sounds like one of them is not at all related to a production that it or secretory product but rather just this surface receptor I think you said it was the amch 1 1100 or something like that yes it has a very fancy name yeah yeah so and that surface protein by itself just stimulates L cells in the um in the osy and that we know that that makes glp one yeah and I think that pathway is probably the least well understood um of of the the other two the the you know short chain fatty acid and the P9 protein have had um I think a lot more work done on so it secretes P9 it secretes propionate propionate gets converted to butyrate by another bacteria which ones there is a a class of um clal strains that will do that secondary conversion and Clum butterum is sort of the most well studied of those got it what about defil is he doing anything good for us there actually don't know we haven't studied whether and maybe people are afraid to bring that into the lab yeah yeah and what does P9 do and so P9 is directly stimulates L cells yes it binds to this IAM 2 receptor on the L cells and stimulates them IAM receptors are receptors that are usually involved in um God if my memory serves me correctly like kind of an immune response right like an inflammatory response well and that is uh you know for we we have not done studies around that but for sure that is a area of heavy interest um yeah by vague recollection I mean we're literally going back 25 years is that when you when a person is uh for example septic right you have all of these IAM modules that lead to you know Vaso dilation leaky capillaries secretion of monocytes out into the peripheral tissue as macroasia um sounds like this is a distinct process here yeah well I mean and and maybe I should say too like I don't know how much of this is tied to that process but the other thing that not not only does acran stimulate uh these L cells to produce gop1 but acran has another role which maybe is very much tied to this um you know which is that uh it it helps regulate the mucin layer and so that mucin layer turns out to be super important for uh if it gets too thin or if it's too thick it's it's it's a real this so-called leaky gut or GI issues that that become a result of not having enough acromania is really that you have too thin of a mucin layer and so you start to get um you know the ability for pathogens to infiltrate and then also obviously for these molecules to secrete out and then tell me what's the fate of the butyrate made of the propionate it binds to these G protein coupled receptors um and that's also what stimulates the L cells to then go release glp1 got it so sort of multiple methods to multiple of these small molecules that you know uh are the signaling molecules for these receptors on the L cells so all roads point to more acromania more glp1 what differs from someone taking OIC is they just have a mega high dose of glp1 all the time and what you're talking about here is as you said kind of a waxing and waning dose of glp1 that is more physiologic because it comes with your meal that's right one would not expect this type of intervention to produce the amount of weight loss you would see with carpet bombing somebody with glp1 absolutely not and and one of the other big differences is that the you know gp1s are injected so you're it's going right into the bloodstream whereas here you know it's it's a microbiome effect to your point you get the waxing and waning sort of more physiologically relevant uh but it's not going to be the same as just hammering a bunch of gop1 straight into the bloodstream all the time all day all night so um yeah yeah so so again again this is so so now let's talk about the data so what was what was the first study that demonstrated that acromania could play a role in from an intervention perspective from um impact imp acting metabolism VAV blood sugar yeah some of the earliest studies are really done I mean this first of all was discovered by Dr Lee Kaplan over at MGH — and he's a bariatric surgeon and so his initial interest was you know what's what's happening to the microbiome we do the bariatric surgery and kind of came to really be one of the first people to really look at these microbes and discovered that acromania — appeared to be you know associated with or inversely associated with obesity and then started these inv vitro studies to figure out like what is it doing so you know the the work really has to go credited back to him in the early 2000s and and I want to point out one of the observations that came from his work which is a really remarkable observation which is — at least as far as the ru and Y gastric bypass which is a real organization a reorganization of the plumbing — of a person's gut that you took a person who was obese with type 2 diabetes”

“and by the way there are two strains um there are only two strains to be able to directly stimulate gp1 one one is acromania mucil the other is chrum butum and they actually act kind of together because Clum butum as its name indicates is a butter rate producer and so um and then gop1 uh is is sort of has multiple uh benefits”

“so it secretes P9 it secretes propionate propionate gets converted to butyrate by another bacteria which ones there is a a class of um clal strains that will do that secondary conversion and Clum butterum is sort of the most well studied of those got it what about defil is he doing anything good for us there actually don't know we haven't studied whether and maybe people are afraid to bring that into the lab yeah yeah and what does P9 do and so P9 is directly stimulates L cells yes it binds to this IAM 2 receptor on the L cells and stimulates them”