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11-06-2016, 07:56 PM   #1
Crohn2357
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Manipulating AIEC in Crohn's patients

Arabinoxylans, inulin and Lactobacillus reuteri 1063 repress the adherent-invasive Escherichia coli from mucus in a mucosa-comprising gut model


http://www.nature.com/articles/npjbi...+International
...L. reuteri 1063, LC-AX and IN specifically lowered AIEC numbers in the simulated mucosal environment of the M-SHIME, while they did not affect AIEC numbers in the luminal content. As a possible explanation, supplementation of IN and LC-AX (during 8 days prior to AIEC inoculation) altered the resident mucosal microbiota, especially subdominant groups (lactobacilli and bifidobacteria). Not only did LC-AX and IN increase the mucosal counts of lactobacilli and bifidobacteria, they also altered the species composition of the bifidobacteria. As shown by DGGE, initially the dominant mucosal Bifidobacterium species was B. bifidum, IN specifically stimulated B. adolescentis in mucus and LC-AX specifically stimulated both B. longum and B. adolescentis in mucus. B. longum has been shown to possess a stronger antimicrobial activity against Escherichia coli compared with B. bifidum.26 Also B. adolescentis was shown to be very effective in combating Escherichia coli compared with B. bifidum27 but also compared with many other Bifidobacterium and Lactobacillus species.28 While antimicrobial factors are possibly too diluted in the intestinal content to be effective, the mucosal environment may allow trapping of antimicrobial factors, thereby repressing AIEC. Especially the spatial heterogeneity introduced by the biofilm on top of the mucin layer may result in local accumulation of e.g., acids produced by lactobacilli or bifidobacteria.

...In conclusion, we showed that the M-SHIME technology—using mucin-covered microcosms—provided a detailed insight in the long-term in vitro microbial colonisation of AIEC, an opportunistic pathogen and abundant mucosal microbe. Moreover, it allowed to evaluate the colonisation of a simulated mucus layer in the presence of a resident mucosal and luminal intestinal microbiota. It has to be considered that in this type of studies, the relevance of the data in terms of potential interindividual variability (i.e., different effect of the test products due to a different composition of the gut microbiota) may be questionable. Our aim was to present a technology platform that might be applied on other disease-causing microbes such as food-borne pathogens and to provide evidences on the potential of several pre- and probiotic strategies to repress AIEC from the mucosal compartment. Here we showed—with the microbiota from one donor—that such repression may occur via different mechanisms including the production of reuterin, undissociated lactic acid or adhesion inhibition. The evaluation of the role of the microbiota from different donors on these mechanisms can be an interesting future line of research. We also showed that the incorporation of a mucosal environment in dynamic gut models may be a powerful tool to obtain a more realistic view on processes that drive the gastrointestinal microbiome.
How would it turn out in vivo? To begin with, are probiotics (and prebiotics) even safe for Crohn's patients (who have intestinal permeability dysfunction)? I always stay away from probiotics-prebiotics because of this reason; even on antibiotics I don't take them.

Are there any other ways to manipulate AIEC in Crohn's patients? Does vitamin d supplementation have any effect? In theory it should:

Once inside the host cell, LF82 bacteria can be found in several types of intracellular compartments: individually or in groups within single membrane vacuoles, within damaged vacuoles, or within LC3-positive autophagosomes, which indicates that autophagy restricts a subpopulation of intracellular LF82 bacteria[57]. Nevertheless, it was recently demonstrated that AIEC can abrogate the autophagic process[58]. Intracellular LF82 activates NF-κB, leading to the increased expression of MIR30C and MIR130A in T84 cells and in mouse enterocytes, and the upregulation of these microRNAs reduces levels of ATG5 and ATG16L1, inhibiting autophagy and enhancing the inflammatory response. In turn, defects in autophagy mechanisms related to the ATG16L1 and IRGM genes have been associated with CD patients, and these defects confer an advantage for AIEC to survive inside human cells[57]. Therefore, it is a combination of host deficiency factors and AIEC pathogenicity that determines the fate of intracellular E. coli survival.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133521/
*******
VDR/vitamin D receptor regulates autophagic activity through ATG16L1.
https://www.ncbi.nlm.nih.gov/pubmed/26218741

Vitamin D deficiency enhances adherent invasive Escherichia coli induced barrier dysfunction and experimental colonic injury
https://www.ecco-ibd.eu/index.php/pu...ic-injury.html

Figure: Vitamin D enhances intramacrophage killing of AIEC. 1,25 OH2-vitamin D3 caused dose-dependent decrease in intramacrophage survival of AIEC HM605 in (A) J774A.1 murine macrophages (N = 3, Cuzick\'s test for trend; P < 0.001) and (B) human MDM (N = 3, Cuzick\'s test; P = 0.012). *P < 0.05, ***P < 0.001 Dunnett\'s test versus control.

Nutritional Management of Inflammatory Bowel Diseases: A Comprehensive Guide
https://books.google.com.tr/books?id...in%20d&f=false
******

What about other ways? Can we manipulate AIEC through dietary interventions? Like reducing certain kind of carbohydrates, or any specific micronutrients affecting it?
11-07-2016, 11:46 AM   #2
Crohn2357
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Here, another in vitro study:

Lactobacillus casei DN-114 001 Inhibits the Ability of Adherent-Invasive Escherichia coli Isolated from Crohn's Disease Patients To Adhere to and To Invade Intestinal Epithelial Cells

http://aem.asm.org/content/71/6/2880...e2=tf_ipsecsha

In this, they demonstrated the inhibitory effects of Lactobacillus casei on AIEC in intestinally derived tissue culture cells. It was demonstrated that attachment of AIEC to Caco-2 and Intestine-407 cells was reduced by 47 and 62%, respectively. The authors also showed a depression of cellular invasion by AIEC with preincubation of L. casei by 98.7% in Intestine-407 cells and 89% in Caco-2 cells.

*******************************************

Killing of Escherichia coli by Crohn's Disease Monocyte-derived Macrophages and Its Enhancement by Hydroxychloroquine and Vitamin D

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4894789/

Figure 4: HCQ (Hydroxychloroquine) enhances intramacrophage killing of AIEC. HCQ treatment causes a dose-dependent decrease in survival of intramacrophage AIEC HM605 in (A) J774A.1 murine macrophages (N = 3, Cuzick\'s test for trend P < 0.001) and (B) healthy human MDM (N = 5, Cuzick\'s test; P < 0.001). ***P < 0.001, Dunnett\'s test versus control. C, HCQ did not have a direct bactericidal action as observed by growth in broth, measured at OD600 nm (N = 3).

About Hydroxychloroquine, take a look at these:
http://www.gidoctor.net/hydro-crohns-ulcerative.php
http://www.crohnsforum.com/showthread.php?t=48991

Last edited by Crohn2357; 11-07-2016 at 12:24 PM.
11-07-2016, 11:17 PM   #3
xeridea
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What about other ways? Can we manipulate AIEC through dietary interventions? Like reducing certain kind of carbohydrates, or any specific micronutrients affecting it?
Radish seeds contain the compound Raphanin, an antimicrobial that was shown to be effective against both Gram-negative and -positive bacteria, including E. Coli and even mycobacterium such as tuberculosis. I haven't found any recent research with most of the citations dating back to the middle of last century, so maybe it was folk medicine that was dismissed. I read somewhere that juice from black radishes used as a retention enema is pretty effective in calming UC symptoms.
11-08-2016, 05:17 AM   #4
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I haven't eaten radishes for years, I was thinking of buying some today, until seeing these studies revealed by a quick research:

Radish Sprout Factory Outbreak of Escherichia Coli O157
http://www.sproutnet.com/Factory-Out...of-Escherichia

Factory outbreak of Escherichia coli O157:H7 infection in Japan.
Emerg Infect Dis 1999 May-Jun;5(3):424-8

To determine the cause of a July 1996 outbreak of Escherichia coli O157:H7 among factory workers in Kyoto, Japan, we conducted cohort and case-control studies. Eating radish sprout salad during lunch at the factory cafeteria had been linked to illness. The sprouts were traced to four growers in Japan; one had been associated with an outbreak of E. coli O157:H7 among 6,000 schoolchildren in Sakai earlier in July.
During May through August 1996, approximately 10,000 cases of Escherichia coli O157:H7 infection associated with at least 14 separate clusters were reported in Japan (1,2). Most cases occurred in school-age children. One cluster was a large outbreak in Sakai City, Osaka Prefecture, involving more than 6,000 primary school children. The outbreak started on July 13, 1996, and an investigation suggested that radish sprouts were the most likely cause (2,3).
An outbreak also occurred in a factory in Kyoto, approximately 50 km from Sakai City. On July 17, 1996, a 24-year-old male factory worker went to a local clinic with diarrhea. The next day, a second worker came to the clinic with diarrhea. Bloody diarrhea and hemolytic uremic syndrome (HUS) subsequently developed in both patients, and stool cultures from each yielded E. coli O157:H7. On July 21, a third worker died of HUS-associated encephalopathy; his stool culture later yielded E. coli O157:H7. All three workers had recently eaten meals at the factory cafeteria. To identify a possible food vehicle, we conducted an epidemiologic investigation.
---
https://books.google.com.tr/books?id...20coli&f=false
http://aem.asm.org/content/77/18/6680.full
The source of pathogenic bacteria on sprouts is thought to originate largely from seeds rather than the contamination of sprouts during or after production
But then I guess, E. Coli contamination is common with vegetables grown in soil.
11-08-2016, 02:50 PM   #5
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For what it's worth, sprouts are notorious for causing foodborne illnesses. From the FDA: "Unlike other fresh produce, seeds and beans need warm and humid conditions to sprout and grow. These conditions are also ideal for the growth of bacteria, including Salmonella, Listeria, and E. coli."
11-08-2016, 03:02 PM   #6
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FIMH inhibitors cranberry and ceylon cinnamon but not cassia cinnamon.
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Learn How Fecal transplants restore good bacteria that regulate inflammation to induce remission and how it has potential to be a cure for IBD in the future. Follow the link below.
http://www.crohnsforum.com/showthread.php?t=52400
11-08-2016, 03:35 PM   #7
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I use propolis tincture for my Crohn's, and I find it very effective.

Antimicrobial Effects of Propolis Extracts on Escherichia coli and Staphylococcus aureus Strains Resistant to Various Antibiotics and Some Microorganisms.


https://www.ncbi.nlm.nih.gov/pubmed/19236174

[Antimicrobial activity of soft and purified propolis extracts].

https://www.ncbi.nlm.nih.gov/pubmed/19142056

Another bee product, royal jelly had helped me a lot, but I was allergic to it so I stopped taking it.

I've also heard good things about Swedish tincture against Crohn's (and UC).

https://en.wikipedia.org/wiki/Swedish_bitters

I recommend these (though I don't have a first hand experience with Swedish tincture) to anyone with Crohn's disease.
11-08-2016, 07:18 PM   #8
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FIMH inhibitors cranberry and ceylon cinnamon but not cassia cinnamon.
This reminded me of an apple-cinnamon tea I used to drink, I'll buy them again, thanks.
11-11-2016, 10:52 AM   #9
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These researchers are proposing using colicins as a narrow spectrum antibiotic specifically targeting AIEC. Colicin is a bacteriocin (what bacteria excrete to kill off competing species) specifically targeting E. Coli. They have shown specific variants of colicins that effectively target AIEC be they in biofilm, intracellular or within macrophages, and demonstrated that their targeted approach is in many cases more powerful than currently available broad-spectrum antibiotics.

They have pulled a patent on this approach to be used in Crohn's patients, and propose delivery of the compound directly, or via probiotics containing species that can excrete the targeted colicin variants.

Also, since bacteriocins are already naturally produced by species in the gut, it makes the path to regulatory approvals easier.

I hit upon this while reading another paper describing the spraying of colicins on vegetables to greatly reduce the chances of them being contaminated with pathogenic E. Coli.
11-12-2016, 07:01 AM   #10
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... Colicins could potentially be delivered to patients with
CD to reduce or eliminate AIEC colonization in the form of
a colicin-producing probiotic. To test the ability of a nonpathogenic
E. coli colicin–producing strain to kill LF82 biofilms, we
added a colicin E1–producing strain (E. coli W3110 pColE1) to
established LF82 biofilms. Viable LF82 cells were counted after
1, 2, 4, 6, and 24 hours of exposure to the E1-producing strain.
At 1 hour after addition of W3110 pColE1, close to 90% of
LF82 biofilm-associated cells were killed, and this rose to
99.6% after 24 hours (Fig. 2). Addition of E. coli W3110 lacking
the colicin E1–encoding plasmid failed to reduce the survival of
the LF82 biofilm population at any of the time points tested
(Fig. 2). These data show that the concentration of colicin produced
by naturally occurring colicin-producing bacteria is suffi-
cient to eradicate mature E. coli biofilms.

...Overall, the selectivity and potent activity of colicins
suggest that they could be used to effectively eradicate a specific
bacterial pathogen, such as AIEC, while preserving the bacterial
population that constitutes the normal healthy microbiome. In
light of current concerns over antibiotic resistance, they also
represent a novel class of antimicrobials that have the potential
to treat a wide range of resistant gram-negative infections.
Furthermore, because of the availability of diverse colicins,
which target a number of different uptake pathways, the use of
“colicin cocktails” and combination therapies could be used to
limit the emergence of resistance.
This is exciting. I hope we can see this on the market.
Preferably, the pharmaceutical composition is formulated for oral administration. The pharmaceutical composition may be formulated as a food product.
https://www.google.com/patents/WO2014009744A1?cl=en

It somehow reminded me the probiotic brand Mutaflor.
https://www.researchgate.net/publica...'s_disease

Found this one, but can't get the full text.
http://www.tandfonline.com/doi/abs/1...65528609011124

Colicinogeny means: "The bacterial property of producing a colicin."

The results are believed to be proof of cellular hypersensitivity of IBD patients to colicins of their own Escherichia coli strains. The importance of this finding must be further clarified.

Last edited by Crohn2357; 11-12-2016 at 07:37 AM.
11-13-2016, 04:31 PM   #11
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I want to repeat my question here: are probiotics safe to take for people with Crohn's disease?

I know this is a very complex subject and still has a lot of unknowns but this question stems from the question "as people with gut issues, should we take probiotics?"

How should we act on this issue? You know, even not acting is a kind of acting. So how can I justify my action on this, namely not taking probiotics, or for other people taking it, then taking probiotics... on a scientific basis?

Is it sensible to take probiotics at this point? I guess our answer would be "we don't know (enough) yet, more studies are needed..."

Do you have any other answers on this subject?
Anyone?
11-13-2016, 09:13 PM   #12
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Here we go, this one is new and is similar to the article you shared, xeridea:

Microcins mediate competition among Enterobacteriaceae in the inflamed gut


http://www.nature.com/nature/journal...ture20557.html

About this study:
http://ibdnewstoday.com/2016/11/08/p...bd-mouse-study
http://medicalxpress.com/news/2016-1...-gut-mice.html

The probiotic e.coli they used (Escherichia coli strain Nissle 1917 [EcN]) is the Mutaflor I wrote earlier.

These researchers on the other hand, say:
The observed inhibition of invasion was not due to the production of microcins by the Nissle 1917 strain because its isogenic microcin-negative mutant SK22D was as effective as the parent strain.
http://femsim.oxfordjournals.org/content/40/3/223.long

For more information on this bacterium, here is a detailed review article:
The non-pathogenic Escherichia coli strain Nissle 1917 – features of a versatile probiotic
http://www.microbecolhealthdis.net/i...File/7512/8855
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