Is there a lab test? For circulating lipopolysaccharide or LPS. Is there a commercially available lab tests available that people can utilize to measure this? Is

my mic. Do I need to stand by this room could. Okay. So the there is a lab test for circulating endotoxin and it's notoriously terrible because it's like false. Positives are so easy. So I mentioned the lactulose to man Mannitol ratio that is a much. I think more accurate biomarker of intestinal permeability, which would I mean directly measuring LPS would be great. But until we have a better sensitivity, a say, I think that it's It's prone to false positivity. So

I have a question, just the button. Sorry for intestinal permeability. We've connected with a group that are using Peg 400 as one of the tests and I would like to get your opinion on that. You

know, I don't know much about that one. So I'll say beyond the scope of my knowledge.

You have a question. If there's a role with nonsteroidals in affecting and test. Sternal permeability. Great

question. I don't know the answer. I think that's a really interesting. In fact, there may be a literature on. I just am not aware of. Next

week at a couple of comments. And a question, the first to really question myself as some colleagues, published a paper recently where we talked about in part alternative metabolic pathways in enterocytes and you see based on the preclinical data that we have. So far. The MCT one is expressed on the basolateral membrane of entire site, so they can take up ketones from circulation. And actually, the common pathway with butyrate is a see to acetyl co a before it goes. Is the mitochondria, so they actually have converging metabolic pathways. So we think that ketones can be used to fuel entire sites. The the second thing when you're talking about LPS. I think what you're really talking about is e.coli LPS because that's what's used experimentally and it's really good at developing inflammation. I do it in my lab. I was doing it on Monday. However, there's you know, LPS on any type of Gram-negative. And there's an increasing body of literature that says that actually LPS from various bacteria directly communicating with the immune system that immunomodulatory. This is our gut talking to us. And so, just talking about LPS go, you know, increasing in the blood and that being bad. I don't think is really right and pretty much everything that we do increases circulating up yet. So you go for a 30 minute Jog and you'll increase, intestinal permeability will increase FPS. And so where the rubber really meets the road is in metabolic. Disease because it's only when you are insulin resistant that having elevated, LPS is an issue because being insulin resistant, the first place increases circulating LPS, but then you also have a scenario where things like transient increases in LPS, like postprandial endotoxemia. You don't have the beneficial anti-inflammatory effects of an insulin Spike to counteract that and then you also going to have things like a discordant lip balm like protein profile, where you can have more small dense LDL where LPS is going to bind to and not be cleared. So So, I wonder if we should be focusing Less on LPS, because we're always going to have someone. It's always going to go up intermittently. And if we just actually do the things that we know work to improve insulin resistance, then that's really going to solve the issue. I

think that you brought up some really interesting points. I think, for me the way, like looking at the effect of The toll-like receptors and understanding toll-like receptor activation from LPS. And I think, you know, there with anything, there's a hormetic stress kind of effect, right? Like, you can go exercise and have a little bit of Personal permeability and it's a type of exercise. We have a whole host of beneficial adaptive responses that are going to counter that. You're so your net effect is going to be lower inflammation. Right? Even if toll-like receptors are being activated on immune cells and liver cells and muscle tissue and brain, right, you know, in the microglia, for example, so I think there's a context is important. And so it's not like the same as if you have someone who has, you know, a chronic low level of constant, LPS leakage, but I do think that The toll-like receptor and looking at the effect of toll-like receptor activation and The Chronic Insidious type of activation of. It is kind of more what I'm thinking, you know, I think that's kind of connecting them in the sense of the more sort of chronic low-grade Activation. So so yeah, I think that, I think that you brought up really, really interesting points. And thank you for telling me about the beta-hydroxybutyrate, we

have time for two more questions. Maybe

mine will be quick. Is

there a reason why someone With intestinal permeability who we treat with a lot of the things that you said and feels better. They're so

quick often to come back into it versus some people seem

to be like, they just

don't experience intestinal permeability, no matter what they eat or do. Yeah, I mean, I think that even getting to the young gentleman's point, you know, you have a variety of factors that are affecting it and that's kind of why I mentioned with the saturated fat. I mean, you look in the literature and it's like, yep, saturated fat intestinal permeability. 80. But when you start to dive a little deeper, it's like, oh, but the saturated fat was a certain type of this processed oil and maybe it's the pulmonic acid, plus the, you know, refined carbohydrate or maybe it's the alcohol plus the stress, or maybe it's like multiple things in combination with genetics getting to the, you know, personalized response. I mean, some people respond terribly to ketogenic diets and some people respond great. So, I mean, there's always individual variation. There's a lot of communal, there's a lot of contributing factors to health and It is it's hard to just say like there's one villain and there's one like you know, what do you call a good guy or hero? Right.