Definitive on gut biome - lipopolysaccharides and butyrate

[TheresaB]

Researchers rarely speak in definitive terms, but these researchers Link between Alzheimer's disease and gut microbiota is confirmed are pretty definitive.

"Our results are indisputable: certain bacterial products of the intestinal microbiota are correlated with the quantity of amyloid plaques in the brain," explains Moira Marizzoni. "Indeed, high blood levels of lipopolysaccharides and certain short-chain fatty acids (acetate and valerate) were associated with both large amyloid deposits in the brain. Conversely, high levels of another short-chain fatty acid, butyrate, were associated with less amyloid pathology."

The paper referenced by the article is behind a paywall, but here's the link: Short-Chain Fatty Acids and Lipopolysaccharide as Mediators Between Gut Dysbiosis and Amyloid Pathology in Alzheimer’s Disease

[TheBrain]

Researchers rarely speak in definitive terms, but these researchers Link between Alzheimer's disease and gut microbiota is confirmed are pretty definitive.

"Our results are indisputable: certain bacterial products of the intestinal microbiota are correlated with the quantity of amyloid plaques in the brain," explains Moira Marizzoni. "Indeed, high blood levels of lipopolysaccharides and certain short-chain fatty acids (acetate and valerate) were associated with both large amyloid deposits in the brain. Conversely, high levels of another short-chain fatty acid, butyrate, were associated with less amyloid pathology."

The paper referenced by the article is behind a paywall, but here's the link: Short-Chain Fatty Acids and Lipopolysaccharide as Mediators Between Gut Dysbiosis and Amyloid Pathology in Alzheimer’s Disease

Teresa, thanks for sharing this information. I have a vague recollection that ketones can feed colonic cells like butyrate does. I searched the forum to see if I could find confirmation, but there were so many results for ketones and butyrate that I gave up. Do you possibly know if this is true? And might you know if ketones can replace the need for butyrate?

[TheresaB]

Teresa, thanks for sharing this information. I have a vague recollection that ketones can feed colonic cells like butyrate does. I searched the forum to see if I could find confirmation, but there were so many results for ketones and butyrate that I gave up. Do you possibly know if this is true? And might you know if ketones can replace the need for butyrate?

Ketones and butyrate are two different things but I can understand some confusion.

Ketone bodies (ketones) provide fuel (energy) for the body, including the brain. Ketones are produced by the liver. A ketogenic diet is simply one where you eat in a manner that generates ketones. You may remember some folks consume foods containing medium chain triglycerides because they quickly convert to ketones in the liver.

Butyrate is a metabolite that is produced by intestinal microbiota (gut bugs). The intestinal bacteria ferment nondigestible foods to produce short-chain fatty acids: butyrate, acetate, and propionate. Those nondigestible foods are what is known as resistant starches that when fermented act as a prebiotic to feed (provide fuel to) the good bacteria in the gut.

From the wiki, “Butyrate has many health benefits, including: intestinal barrier fortification, ameliorating inflammation and oxidation, cell growth and differentiation, intestinal motility and visceral perception, immune regulation, and ion absorption.”

So producing butyrate is important, particularly with keeping the gut happy (eubiosis – good bugs in control, not dysbiosis when the bad bugs take over) and keeps the gut tight (not leaky, intestinal permeability), thus keeping the brain happy, because a leaky gut leads to a leaky brain (i.e. blood-brain barrier permeability) which introduces toxins and pathogens to the brain thus creating neuroinflammation.

Producing ketones is also important, it provides energy to the brain when brain glucose uptake is impaired, but it does SO MUCH MORE!
Note this slide from Amy Berger's presentation Ketogenic Therapies for Neurological & Neurodegenerative Disorders given this past September that cites 16 known mechanisms of a Ketogenic Diet (KD).

16_mechanisms_of_ketogenic_diet.jpg

One of the benefits mentioned is that ketosis increases butyrate production in the gut. So ketones and butyrate, while different, do go hand in hand!

I read that bullet to say while ketones don't produce butyrate, it helps the gut produce more butyrate. The gut still needs the dietary fiber, the gut bugs can't produce butyrate out of thin air. Remember there is no standard ketogenic diet, it can be carnivore, omnivore, vegan, even just rice and potatoes if you calorie restrict enough.

I like the ketogenic diet recommended by Dr Bredesen, and supported in the wiki, but his second book is much better at defining this, which is one starting with an overnight fast (to kick-start ketosis) eating healthy fats, then good carbohydrates that offer phytonutrients, prebiotics, and probiotics, with adequate animal protein (you may have heard Dr Bredesen often refer to meat as a condiment.)

I hope this helps clarify your thinking.

[TheBrain]

I hope this helps clarify your thinking.

Does it ever! Thank you, Theresa, for your clear, thorough, and thoughtful reply. Much appreciated.

[rrmolo]

Theresa B. You have such a wonderful understanding of this process. In very simple terms, what does a day of 3 meals look like for you. ie, what is a simple breakfast, lunch and or dinner, if you can simplify that much. My husband and I eat the same breakfast and lunch with variations many days. Maybe that happens more often as you get older and are home more. Just trying to keep things easy.

[TheresaB]

Theresa B. You have such a wonderful understanding of this process. In very simple terms, what does a day of 3 meals look like for you. ie, what is a simple breakfast, lunch and or dinner, if you can simplify that much. My husband and I eat the same breakfast and lunch with variations many days. Maybe that happens more often as you get older and are home more. Just trying to keep things easy.

First, I don't eat 3 meals I eat 2 meals. I start my day off with black coffee and tea, but break my fast late in the morning, to try to achieve a 16 hour overnight fast as recommended by Dr Bredesen. The "big" meal is dinner with my husband. Our evening meal always has a big salad and a steamed vegetable, a la Dr Terry Wahls, as shown in this graphic.

000_Wahls protocol.JPG

Otherwise, for ~5 years now we've been following the dietary advice of Dr Steven Gundry, which is the Plant Paradox Diet. We don't follow the keto Plant Paradox diet, but we follow Plant Paradox diet in a manner that we maintain mild ketosis (which is helped by the 16 hour overnight fast.) This diet has reduced by inflammatory markers, improved my HDL, lowered my triglycerides, keeps my oxidized LDL reasonable, maintains a good Omega-6 to -3 ratio and addresses mitochondrial and gut health.

Some resources for more info on this diet, including recipes:

Our wiki: https://wiki.apoe4.info/wiki/Dr_Gundry%27s_Protocol
https://wiki.apoe4.info/wiki/Recipes_from_our_members

Dr Gundry's book: The Plant Paradox

Lectin Free Solutions: https://www.facebook.com/lectinfreesolutions/ "Featuring Plant Paradox Recipes and healthy suggestions to help you reverse heart disease and prevent the ApoE4 gene (Alzheimers) from expressing"

[Family Tree Guy]

Researchers rarely speak in definitive terms, but these researchers Link between Alzheimer's disease and gut microbiota is confirmed are pretty definitive.

"Our results are indisputable: certain bacterial products of the intestinal microbiota are correlated with the quantity of amyloid plaques in the brain," explains Moira Marizzoni. "Indeed, high blood levels of lipopolysaccharides and certain short-chain fatty acids (acetate and valerate) were associated with both large amyloid deposits in the brain. Conversely, high levels of another short-chain fatty acid, butyrate, were associated with less amyloid pathology."

The paper referenced by the article is behind a paywall, but here's the link: Short-Chain Fatty Acids and Lipopolysaccharide as Mediators Between Gut Dysbiosis and Amyloid Pathology in Alzheimer’s Disease

Hi TheresaB- not sure if you already knew but lipopolysacdharides (LPS) are one of the prominent virulence factors secreted by Porphyromonas gingivalis (Pg) (the more famous cousin of LPS are the gingipains, which Cortexyme is currently running clinical trial against for mild-moderate AD, and 2/3rd of the trial participants are E4 carriers). One way to have high amounts of LPS found in your gut is to have an active systemic infection with Pg. Although Pg enters your system through the mouth, it quickly spreads even if you get good dental care.

[TheresaB]

One way to have high amounts of LPS found in your gut is to have an active systemic infection with Pg.

Yes, Family Tree Guy, that is one way LPS can reach the bloodstream where it produces inflammation.

Although LPS is an endotoxin, it resides in all of us without issue as long as it remains within the gut. It is when it is released into the bloodstream that inflammation ensues. There are 3 ways LPS is released from the gut:

• 1. Infection. You mentioned one way we can have an infection, P gingivalis, of course there are other sources of infection
  
  2. Leaky gut
  
  3. Chylomicrons - large triglyceride-rich lipoproteins, the LPS “hitch a ride” on these “fat transporters” from high fat meals