02-07-2013, 04:57 PM   #1
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Inflammation feeds E. coli

Inflamed intestines produce their own brand of fertilizers, which nourish E. coli and other disease-associated bacteria, a new study shows.

Everyone carries a small amount of E. coli in their intestines, and it normally causes no problems. But compared with people who have healthy colons, people with inflammatory bowel diseases such as ulcerative colitis or Crohn’s disease harbor a mix of intestinal microbes that is heavier on E. coli.

No one knew whether the disease or the altered microbial mix came first. The new study, published in the Feb. 8 Science, takes a step toward unraveling that chicken-or-egg tangle. Inflammation, a process the body usually uses to kill microbes, may instead feed “bad” bacteria, further inflaming the gut.

Scientists know that during inflammation, tissues produce chemicals such as nitric oxide and superoxides, which can break DNA and ravage bacterial cells. But in experiments involving mice, Andreas Bäumler of the University of California, Davis and colleagues discovered that when the chemicals react with each other, they can produce nitrates and other compounds that some bacteria use for fuel.

The analysis suggests that some bacteria take advantage of changes in a host’s metabolism to overcome competitors, says David Low, a microbial geneticist at the University of California, Santa Barbara. Understanding how the bacteria do this may eventually lead to new therapies or preventative strategies.

E. coli normally makes up a tiny fraction — usually about 0.1 percent — of the bacteria in the gut, Bäumler says. In an inflamed colon, the bacteria can bloom to about 10 percent of the intestinal microbe mix, crowding out friendlier types.

To find out how E. coli and related bacteria accomplish the takeover, Bäumler and his colleagues inflamed mice’s bowels by injecting a chemical irritant. They found that inflamed colons, but not healthy ones, produce nitrate.

Scientists know that most bacteria in the gut aren’t equipped to consume nitrate. But E. coli and related bacteria can. These bacteria contain enzymes that use nitrate and other chemicals to produce energy. That gives them a food source other bacteria can’t use.

Bacteria fight vigorously over nutrients in the colon, Bäumler says. “If you can sidestep the competition, you have a huge advantage.” His team found that mutant E. coli strains that can’t use nitrate for food also can’t outcompete normal bacteria.

Inflammation is essential to E. coli’s colon-domination strategy, the researchers found. Mice with normal colons didn’t experience E. coli overgrowth. Blocking an enzyme that produces nitric oxide, nitrate’s precursor, in intestinal cells also stopped the E. coli incursion in inflamed guts, the researchers found.

Taken together, the results suggest that removing inflammation-generated nitrate or blocking E. coli’s ability to use it could limit the bacterium’s growth in the intestines. But nitric oxide plays important roles throughout the body such as regulating blood vessel dilation, so disabling the enzyme that produces it may not represent a good strategy for treating bowel diseases.

“You can’t just take a sledgehammer and knock out something like that without having a lot of other repercussions,” Low says.

Bäumler says his group is working on potential treatments that would restore the normal microbial mix by preventing E. coli and related bacteria from using the nitrate.
02-07-2013, 07:24 PM   #2
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kiny's Avatar
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Thank you.

Would be nice if they used the word AIEC over the broad E Coli term, since I assume that is what they are talking about. E Coli aren't an issue in crohn's disease, most strains are noninvasive, it's only a small percentage of those strains that are invasive, the AIEC subset. Controls have them too, but they become pathogens who exploit the inflammation in people with crohn's disease. Probiotics like E Coli nissle don't worsen crohn's disease, it's genotoxic, but they don't make the disease any worse. I think if you have mucosal breakdown AIEC with their nasty flagella would start exploiting the inflammation, they don't mind a highly active macrophage environment, they subvert autophagy and they thrive to exploit the inflammation. They would act like very pathogenic intracellular bacteria, move into the macrophage, duplicate while subverting autophagy, move out of the macrophage, vulnerable for a very short time and replicate again and again. The noninvasive E Coli likely limit the progress AIEC makes to colonise the cell wall.

They find AIEC a lot in people with crohn's disease. And you need good antibiotics and multiple antibiotics to kill them because in most cases you would just get resistance, they live in biofilms and they easily resist many antibiotics, they're intracellular pathogens that live in cells, they would be in macrophages, dentric cells, in the regular epithelial cells, stiking onto the gut wall and invading submucosa. They are super nasty and if you can't correctly perform autophagy in the macrophage you're pretty much screwed until someone gives you an antibiotic to control them or you force apoptosis of the activated leukocyte that harbour them, which is I think what stuff like infliximab is doing. If you don't control them you would get more and more leucocyte homing into the gut from signaling macrophages, more and more inflammation from the cytokine and AIEC don't care one iota, they're having a blast messing up the intestine until you target them since they thrive in inflammatory environments. This isn't the first bacteria that likes an inflammatory environment, there's plent of bacteria that don't mind the innate inflammatory response nor do they mind fevers or nutritional deprivation, they enjoy the inflammatory response just fine and find ways to exploit it.

All of the stuff that helps for crohn's disease seems to work the same way, they are all inducing apoptosis of activated leucocyte, even stuff like pentasa does it even though it's far less powerful. Everything that just lowers the inflammatory response is useless for crohn's disiease, all TNF-alpha blockers that simply lower TNF-alpha do not help for crohn's disease, they all failed in trials, they help in autoimmune diseases but they do not help for crohn's disease, it's only the ones inducing the apoptosis of activated leukocyte that are working, 6mp does the same thing, it's inducing apoptosis.

I think personally that they are all antimicrobial agents in people with crohn's diease. Their method of action is not lowering cytokine response or lowering inflammatory response, they are actively causing apoptosis and actively killing AIEC, mycobacteria, whatever your notiong of crohn's disease is.

Stuff like infliximab and humira are not just TNF-alpha blockers, they bind to the cytokine and that causes apoptosis of the cell, and it becomes an antimicrobial.

Anyone got the full study to this, don't see where it's from.

Last edited by kiny; 02-07-2013 at 10:43 PM.
02-07-2013, 10:45 PM   #3
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Wish I could write in my own language sometimes since I often misspell or use the wrong words after i reread it, I tend to edit like 2 times before I'm done. I hope the spelling and words are correct now.
02-07-2013, 11:03 PM   #4
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Thank you for this Kiny
Your spelling and words are perfect.
I always look forward to what you are discussing.

Hugs and best wishes
02-10-2013, 12:48 PM   #5
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Join Date: Jun 2012
Location: Pennsylvania
Ways to inhibit iNOS. Will add more when I find them.Looks like a lot of stuff.
The iNOS would also apply to Crohn's. If we can inhibit inos this will inhibit
NO. If we inhibit NO then hopefully ecoli can be inhibited. EVOO an olive leaf extract seem to be the easiest way to go.

Old Mike

First what is it.








here is an interesting long thread on a body building forum.






evoo-olive leaf extract seems to contain high amounts of oleuropein which is hydrolyzed

into hydroxytyrosol in the digestive system,as far as I can tell.


02-12-2013, 03:32 PM   #6
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the same but with another words! *)
02-21-2013, 12:33 AM   #7
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PollyH's Avatar
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Niacinamide reduces the nitric oxide and intestinal inflammatory response to the LPS (lipopolysaccaride) found in the shell of gram negative bacteria like E. coli.
02-21-2013, 01:02 AM   #8
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Join Date: Sep 2009
why cant both be true?

inflammation can be caused by bacteria, AND bacteria can utilize inflammation to survive?

who says it has to be either or the other? there is evidence for both being true. if we do real science, we dont make up rules about nature, we discover them.

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