Saturated fat enhances endotoxemia. Should we even care?

[Hans]

It's "well-known" that saturated fat increases circulating endotoxin more than MUFA or PUFA. For that reason, people recommend avoiding saturated fat to lower inflammation (since endotoxin causes inflammation).

However, when looking at cytokine changes, saturated fat is not worse than other fats. It's instead a problem in people with obesity, who are more likely to have gut problems, leaky gut and have enhanced absorption of endotoxin in general.

But this is the study I want to get to. The word endotoxin is misleading. It makes you think there is only 1 kind of endotoxin. But actually different bacteria create different kinds of endotoxin, aka lipopolysaccharides. Some are much more harmful and inflammatory than others. Interestingly, certain endotoxin can actually antagonize the endotoxin receptor, TLR4.

Metabolic endotoxemia is dictated by the type of lipopolysaccharide - PubMed

Lipopolysaccharides (LPSs) can promote metabolic endotoxemia, which is considered inflammatory and metabolically detrimental based on Toll-like receptor (TLR)4 agonists, such as Escherichia coli-derived LPS. LPSs from certain bacteria antagonize TLR4 yet contribute to endotoxemia measured by...

pubmed.ncbi.nlm.nih.gov

"Lipopolysaccharides (LPSs) can promote metabolic endotoxemia, which is considered inflammatory and metabolically detrimental based on Toll-like receptor (TLR)4 agonists, such as Escherichia coli-derived LPS. LPSs from certain bacteria antagonize TLR4 yet contribute to endotoxemia measured by endotoxin units (EUs). We found that E. coli LPS impairs gut barrier function and worsens glycemic control in mice, but equal doses of LPSs from other bacteria do not. Matching the LPS dose from R. sphaeroides and E. coli by EUs reveals that only E. coli LPS promotes dysglycemia and adipose inflammation, delays intestinal glucose absorption, and augments insulin and glucagon-like peptide (GLP)-1 secretion. Metabolically beneficial endotoxemia promoted by R. sphaeroides LPS counteracts dysglycemia caused by an equal dose of E. coli LPS and improves glucose control in obese mice. The concept of metabolic endotoxemia should be expanded beyond LPS load to include LPS characteristics, such as lipid A acylation, which dictates the effect of metabolic endotoxemia."

So the fact that saturated fat might enhance circulating endotoxin, especially the "good" ones, might actually be seen as a good thing. Just make sure your gut is not inflamed ofc.

 

[baccheion]

What opposes, lowers, and/or denatures? ALPL (calcium, magnesium, zinc, vitamin K1, vitamin K2 MK-4, unsaturated fats; and somewhat indirectly, vitamin B6). Vitamin D3 probably also helps. And intermittent fasting.

Either way, the best measure is oxLDL (aka, arterial health).

 

[Hans]

What opposes, lowers, and/or denatures? ALPL (calcium, magnesium, zinc, vitamin K1, vitamin K2 MK-4, unsaturated fats; and somewhat indirectly, vitamin B6). Vitamin D3 probably also helps. And intermittent fasting.

Either way, the best measure is oxLDL (aka, arterial health).

Intestinal alkaline phosphatase is one of the main enzymes that break down LPS. It's generally increased by vitamin D, K2, zinc, etc.

 

[Hans]

Another goldy. The general endotoxin signaling in the gut of a healthy individual is TLR4 antagonism.

"In this study, we performed computational and experimental analyses of healthy human fecal samples to examine the TLR4 signaling capacity of the gut microbiota. These analyses revealed that an immunoinhibitory activity of LPS, conserved across the members of the order Bacteroidales and derived from an underacylated structural feature, silences TLR4 signaling for the entire consortium of organisms inhabiting the human gut... These findings challenge the current belief that robust TLR4 signaling is a feature of the microbiome and demonstrate that microbiome-derived LPS has the ability to facilitate host tolerance of gut microbes."

"This study shows that an important proinflammatory pathway that is commonly triggered by pathogenic bacteria upon interaction with the host is, in fact, actively repressed by the bacteria of the gut microbiome, supporting the idea that beneficial microbes themselves contribute to the immune tolerance in support of homeostasis. These findings are important for two reasons. First, many currently assume that proinflammatory signaling by lipopolysaccharide is a fundamental feature of the gut flora. This assumption influences greatly how host-microbiome interactions are theoretically modeled but also how they are experimentally studied, by using robust TLR signaling conditions to simulate commensals. Second, elucidation of the mechanisms that support host-microbe tolerance is key to the development of therapeutics for both intestinal and systemic inflammatory disorders."

So this whole concept to use anti-biotics to keep bacteria low in general is flawing imo. Just keep inflammation low and keep the gut healthy and your bacteria should look after you. The problem comes in when scientists inject animals with LPS from pathological bacteria such as E. coli.
When you optimize digestion, bile flow, transit time, vitamin D and other nutrients, your microbiome should be in check without the need for bacteria lowering compounds. P.S.

 

[VitoScaletta]

Another goldy. The general endotoxin signaling in the gut of a healthy individual is TLR4 antagonism.

"In this study, we performed computational and experimental analyses of healthy human fecal samples to examine the TLR4 signaling capacity of the gut microbiota. These analyses revealed that an immunoinhibitory activity of LPS, conserved across the members of the order Bacteroidales and derived from an underacylated structural feature, silences TLR4 signaling for the entire consortium of organisms inhabiting the human gut... These findings challenge the current belief that robust TLR4 signaling is a feature of the microbiome and demonstrate that microbiome-derived LPS has the ability to facilitate host tolerance of gut microbes."

"This study shows that an important proinflammatory pathway that is commonly triggered by pathogenic bacteria upon interaction with the host is, in fact, actively repressed by the bacteria of the gut microbiome, supporting the idea that beneficial microbes themselves contribute to the immune tolerance in support of homeostasis. These findings are important for two reasons. First, many currently assume that proinflammatory signaling by lipopolysaccharide is a fundamental feature of the gut flora. This assumption influences greatly how host-microbiome interactions are theoretically modeled but also how they are experimentally studied, by using robust TLR signaling conditions to simulate commensals. Second, elucidation of the mechanisms that support host-microbe tolerance is key to the development of therapeutics for both intestinal and systemic inflammatory disorders."

So this whole concept to use anti-biotics to keep bacteria low in general is flawing imo. Just keep inflammation low and keep the gut healthy and your bacteria should look after you. The problem comes in when scientists inject animals with LPS from pathological bacteria such as E. coli.
When you optimize digestion, bile flow, transit time, vitamin D and other nutrients, your microbiome should be in check without the need for bacteria lowering compounds. P.S.

Well said Hans

 

[ecstatichamster]

I find l Reuteri fantastic. But I still get endotoxin symptoms sometime. Pau d’arco relieves it.

 

[sunny]

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[Apple]

@Hans

This is the kind of stuff you will see on the net, regarding fats and LPSs:
View: https://kahn642.medium.com/metabolic-endotoxemia-the-link-between-the-chronic-diseases-and-the-saturated-fats-you-want-to-eda04c8623e4#:~:text=A%20high%2Dfat%20diet%20results,tract%20and%20enter%20the%20circulation
.