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Large study identifies exact gut bacteria involved in Crohn's disease

Discussion in 'Other Health News and Research' started by Ecoclimber, Mar 12, 2014.

  1. Ecoclimber

    Ecoclimber Senior Member

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    Date:
    March 12, 2014
    Source:
    Cell Press
    Large study identifies exact gut bacteria involved in Crohn's disease

    Summary:

    While the causes of Crohn's disease are not well understood, recent research indicates an important role for an abnormal immune response to the microbes that live in the gut. In the largest study of its kind, researchers have now identified specific bacteria that are abnormally increased or decreased when Crohn's disease develops. The findings, which appear in the March 12 issue of the Cell Press journal Cell Host & Microbe, suggest which microbial metabolites could be targeted to treat patients with this chronic and currently incurable inflammatory bowel disease.

    Twenty-eight gastroenterology centers across North America have been working together to uncover how microbes contribute to the inflammatory cascade of Crohn's disease. Researchers took biopsies from 447 individuals with new-onset Crohn's disease and 221 nonaffected individuals at multiple locations along the gastrointestinal tract and then looked for differences between the two groups. They also validated their methods in additional individuals, resulting in a total of 1,742 samples from pediatric and adult patients with either new-onset or established disease.

    The team found that microbial balance was disrupted in patients with Crohn's disease, with beneficial microbes missing and pathological ones flourishing. Having more of the disease-associated organisms correlated with increasing clinical disease activity. "These findings can guide the development of better diagnostics," says senior author Dr. Ramnik Xavier of Massachusetts General Hospital and the Broad Institute of MIT and Harvard. "More importantly, our study identified specific organisms that are abnormally increased or decreased in disease, which forms a blueprint to develop microbial therapeutics."

    When the researchers analyzed the effects of antibiotics, which are sometimes used to treat Crohn's disease symptoms prior to diagnosis, they found that antibiotic usage in children with Crohn's disease could be counterproductive because it causes a loss of good microbes and an increase in pathological ones.

    The investigators also examined different approaches for measuring gut microbes in patients and found that the bacterial communities in biopsies taken from rectal tissue served as good indicators of disease, regardless of where a patient was experiencing inflammation along the gastrointestinal tract. "This finding is particularly encouraging because it creates the opportunity to use a minimally invasive approach to collecting patient samples for early disease detection," explains first author Dr. Dirk Gevers of the Broad Institute.

    Story Source:

    The above story is based on materials provided by Cell Press. Note: Materials may be edited for content and length.

    Journal Reference:

    1. Dirk Gevers, Subra Kugathasan, Lee A. Denson, Yoshiki Vázquez-Baeza, Will Van Treuren, Boyu Ren, Emma Schwager, Dan Knights, Se Jin Song, Moran Yassour, Xochitl C. Morgan, Aleksandar D. Kostic, Chengwei Luo, Antonio González, Daniel McDonald, Yael Haberman, Thomas Walters, Susan Baker, Joel Rosh, Michael Stephens, Melvin Heyman, James Markowitz, Robert Baldassano, Anne Griffiths, Francisco Sylvester, David Mack, Sandra Kim, Wallace Crandall, Jeffrey Hyams, Curtis Huttenhower, Rob Knight, Ramnik J. Xavier. The treatment-naive microbiome in new onset Crohn's Disease. Cell Host & Microbe, March 2014 DOI: 10.1016/j.chom.2014.02.005
     
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  2. snowathlete

    snowathlete

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    This is encouraging. I have ulcerative colitis and the same sort of problem may exist in that disease as appears to exist in Crohn's. The problem is correcting it. At the moment, even if you figure out that your gut flora is out of balance, you can't necesarily get hold of the 'good' bacterial strains that you need as many are not available on the market. And this also may not be enough to get the bad bacteria under control again anyway.
    Promising research though, and if ME/CFS does turn out to be 'in the gut' then the same lessons learn in IBDs could well result in effective treatments for ME/CFS in the not so distant future.
     
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  3. aimossy

    aimossy Senior Member

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    Wonderful news!!!!
     
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  4. Firestormm

    Firestormm Guest

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  5. Valentijn

    Valentijn Activity Level: 3

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    So in Crohn's disease, these are the bacteria which are increased compared to the controls:
    Enterobacteriaceae
    Pasteurallaceae
    Fusobacteriaceae
    Neisseriaceae
    Veillonellaceae
    Gemellaceae

    And decreased in Crohn's:
    Bacteroidales
    Clostridiales
    Erysipelotrichaceae
    Bifidobacteriaceae

    I don't have Crohn's, but I do have other GI issues and my Bifido is also very low - 0, actually :p
     
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  6. adreno

    adreno 3% neanderthal

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    Well most of those good ones can actually be supplemented. And by taking Resistant Starch, you will cause your beneficial ones to flourish, crowding out the bad ones. Take a look at the Resistant Starch thread, if you haven't already.
     
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  7. xchocoholic

    xchocoholic Senior Member

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    I'd love to see a similar study on pwcs.
     
  8. xchocoholic

    xchocoholic Senior Member

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    Hi @adreno

    The resistant starch thread is too big and confusing now. Got any cliff notes?

    Basically I was wondering why a certain potato starch was being used but couldn't find the answer when I looked.

    What other foods would work?

    Also, it's 4 am here ... zzzz ....

    back to this study ... what about the good yeasts our bodies need? S boulardii has been shown to help with c diff. Is anyone studying these. I know from growing kombucha that yeasts and bacteria can be symbiotic.

    G nite ... x
     
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  9. adreno

    adreno 3% neanderthal

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    The main point is that RS is food for your biome (not for you), and it is lacking in the modern diet. Taking RS is going to have way more dramatic effects than just using probiotics. The potato starch has too be raw for it to retain the RS, that's all.

    All the basics is pretty much explained in the first post, you don't have to read the whole thread:

    http://forums.phoenixrising.me/inde...ge-is-it-the-key-weve-been-looking-for.26976/
     
    Last edited: Mar 13, 2014
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  10. xchocoholic

    xchocoholic Senior Member

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    I brought my bifido up with Metagenics bifido plus? . Lactobacillus was still low.

    I can't remember my other bacteria counts but my candida counts vary from high to low and I've yet to notice any difference physically.

    I stopped having candida symptoms around 2006 tho. One year post elimination diet. Maybe because Gluten was suppressing my immune system. Tc ... x
     
    Last edited: Mar 13, 2014
  11. xchocoholic

    xchocoholic Senior Member

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  12. xchocoholic

    xchocoholic Senior Member

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    Hi again. @adreno

    I just tried to read that post and remembered why I lost interest. Wow.

    Is there a version that DOESN'T read like a sales pitch or isn't immediately defensive ?

    Just the facts please.

    Also, I haven't looked yet to try to understand the difference, but prebiotics have been available for years. I take Blue Bonnet probiotics with prebiotics.

    Tx .. x
     
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  13. Ecoclimber

    Ecoclimber Senior Member

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    Well, this whole topic can be expanded into several similar topics on microbes in the research listings below:

    Recommend that people with digestive health issues reduce, NOT increase, hard to digest fermentable carbohydrates to control symptoms of IBS, acid reflux and other digestive health issues related to dysbiosis (general imbalance of gut microbes) and SIBO (small intestinal bacterial overgrowth).

    Resistant starch is a type of starch that resists digestion. Starch in general is a large complex carbohydrate used by plants such as oats, corn, potatoes, wheat, rice, nuts, legumes and some fruits such as bananas to store energy. Foods that contain starch make up a large part of many people’s diet. For many years it was believed that starch was completely digested and absorbed in the small intestine. But studies published in the 1980s, based on hydrogen breath testing, showed that oats, wheat, potatoes, corn, and beans contained 10 to 20% malabsorbed, fermentable material.

    Beneficial microbes are 'selected and nurtured' in the human gut

    [​IMG]
    Confocal fluorescence image of bacteria growing in the lumen on top of host epithelial cells. Sample taken from the cecum of a laboratory mouse, where there has been no intentional manipulation of the animal's microbiotia. Epithelial and bacterial cells in green (DNA stained with Sytox green), and the epithelial border brush in blue (actin stained with Alexa-647-phalloidin) from [83].
    Credit: Jonas Schluter, Kevin R. Foster. The Evolution of Mutualism in Gut Microbiota Via Host Epithelial Selection. PLoS Biology, 2012; 10 (11): e1001424 DOI: 10.1371/journal.pbio.1001424
    Animals, including humans, actively select the gut microbes that are the best partners and nurture them with nutritious secretions, suggests a new study led by Oxford University, and published November 20 in the open-access journal PLOS Biology.


    The Oxford team created an evolutionary computer model of interactions between gut microbes and the lining (the host epithelial cell layer) of the animal gut. The model shows that beneficial microbes that are slow-growing are rapidly lost, and need to be helped by host secretions, such as specific nutrients, that favour the beneficial microbes over harmful ones.

    The work also shows that the cost of such selectivity is low: the host only needs to use a very small amount of secretions to retain beneficial microbes that would otherwise have been lost.

    "The cells of our bodies are greatly outnumbered by the microbes that live on us and, in particular, in our gut," said Professor Kevin Foster of Oxford University's Department of Zoology, an author of the new paper. "We know that many gut microbes are highly beneficial to us, protecting us from pathogens and helping us with digestion, but quite how such a beneficial mutual relationship evolved, and how it is maintained, has been something of a mystery."

    "This research highlights the importance of growth-promoting substances in our ability to control the microbes that live inside us. It shows that nutrients are more powerful when released by the host epithelial cell layer than when coming from the food in the gut, and suggests that controlling our microbes is easier than was previously thought."

    Jonas Schulter, also of Oxford University's Department of Zoology and first author of the paper, said: "The inside of our gut is rather like a war zone, with all kinds of microbes battling it out for survival and fighting over territory. Our study shows that hosts only have to secrete a small quantity of substances that slightly favour beneficial microbes to tip the balance of this conflict: it means that favoured microbial species that would otherwise be lost don't just survive on the epithelial surface but expand, pushing any other strains out."

    The team's simulations show that cells affected by host epithelial selection are least likely to be lost, and instead persist longest, causing 'selectivity amplification', whereby relatively tiny changes instituted by the host (in this case a very small amount of secretions of certain compounds) can be amplified to produce a large-scale effect.

    The study may have wider implications than the human gut: selectivity amplification may occur in a range of other interactions between hosts and microbes, including the microbes that grow on the surface of corals and the roots of plants.

    Story Source:

    The above story is based on materials provided by Public Library of Science. Note: Materials may be edited for content and length.

    Journal Reference:

    1. Jonas Schluter, Kevin R. Foster. The Evolution of Mutualism in Gut Microbiota Via Host Epithelial Selection. PLoS Biology, 2012; 10 (11): e1001424 DOI: 10.1371/journal.pbio.1001424

    Microbes help to battle infection: Gut microbes help develop immune cells, study finds
    Date:
    March 12, 2014
    Source:
    California Institute of Technology

    Summary:
    Beneficial gut bacteria are necessary for the development of innate immune cells -- specialized types of white blood cells that serve as the body's first line of defense against invading pathogens -- new research has found. The research suggests that a healthy population of gut microbes can actually provide a preventative alternative to antibiotics.

    [​IMG]
    An artist’s representation of gut microbes promoting hematopoiesis.
    Credit: Arya Khosravi and Wesley McBride/Caltech
    [Click to enlarge image]
    The human relationship with microbial life is complicated. At almost any supermarket, you can pick up both antibacterial soap and probiotic yogurt during the same shopping trip. Although there are types of bacteria that can make us sick, Caltech professor of biology and biological engineering Sarkis Mazmanian and his team are most interested in the thousands of other bacteria -- many already living inside our bodies -- that actually keep us healthy. His past work in mice has shown that restoring populations of beneficial bacteria can help alleviate the symptoms of inflammatory bowel disease, multiple sclerosis, and even autism. Now, he and his team have found that these good bugs might also prepare the immune cells in our blood to fight infections from harmful bacteria.

    In the recent study, published on March 12 in the journal Cell Host & Microbe, the researchers found that beneficial gut bacteria were necessary for the development of innate immune cells -- specialized types of white blood cells that serve as the body's first line of defense against invading pathogens.

    In addition to circulating in the blood, reserve stores of immune cells are also kept in the spleen and in the bone marrow. When the researchers looked at the immune cell populations in these areas in so-called germ-free mice, born without gut bacteria, and in healthy mice with a normal population of microbes in the gut, they found that germ-free mice had fewer immune cells -- specifically macrophages, monocytes, and neutrophils -- than healthy mice.

    Germ-free mice also had fewer granulocyte and monocyte progenitor cells, stemlike cells that can eventually differentiate into a few types of mature immune cells. And the innate immune cells that were in the spleen were defective -- never fully reaching the proportions found in healthy mice with a diverse population of gut microbes.

    "It's interesting to see that these microbes are having an immune effect beyond where they live in the gut," says Arya Khosravi, a graduate student in Mazmanian's lab, and first author on the recent study. "They're affecting places like your blood, spleen, and bone marrow -- places where there shouldn't be any bacteria."

    Khosravi and his colleagues next wanted to see if the reduction in immune cells in the blood would make the germ-free mice less able to fight off an infection by the harmful bacterium Listeria monocytogenes -- a well-studied human pathogen often used to study immune responses in mice. While the healthy mice were able to bounce back after being injected with Listeria, the infection was fatal to germ-free mice. When gut microbes that would normally be present were introduced into germ-free mice, the immune cell population increased and the mice were able to survive the Listeria infection.

    The researchers also gave injections of Listeria to healthy mice after those mice were dosed with broad-spectrum antibiotics that killed off both harmful and beneficial bacteria. Interestingly, these mice also had trouble fighting the Listeria infection. "We didn't look at clinical data in this study, but we hypothesize that this might also happen in the clinic," says Mazmanian. "For example, when patients are put on antibiotics for something like hip surgery, are you damaging their gut microbe population and making them more susceptible to an infection that had nothing to do with their hip surgery?"

    More importantly, the research also suggests that a healthy population of gut microbes can actually provide a preventative alternative to antibiotics, Khosravi says. "Today there are more and more antibiotic resistant superbugs out there, and we're running out of ways to treat them. Limiting our susceptibility to infection could be a good protective strategy."

    Story Source:

    The above story is based on materials provided by California Institute of Technology. The original article was written by Jessica Stoller-Conrad. Note: Materials may be edited for content and length.

    Journal Reference:

    1. Arya Khosravi, Alberto Yáñez, Jeremy G. Price, Andrew Chow, Miriam Merad, Helen S. Goodridge, Sarkis K. Mazmanian. Gut Microbiota Promote Hematopoiesis to Control Bacterial Infection. Cell Host & Microbe, March 2014 DOI: 10.1016/j.chom.2014.02.006
    Cite This Page:

    California Institute of Technology. "Microbes help to battle infection: Gut microbes help develop immune cells, study finds." ScienceDaily. ScienceDaily, 12 March 2014. <www.sciencedaily.com/releases/2014/03/140312132632.htm>.
     
    Last edited: Mar 13, 2014
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  14. adreno

    adreno 3% neanderthal

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    Well, I don't feel the way you do. I've pointed you to the information, it's up to you if you are interested or not. There is a lot of research (facts) compiled on the freetheanimal blog, which is indexed in the first post (as I said), but here are the links for you again:

    http://freetheanimal.com/2013/06/re...e-getting-somewhere-and-talking-shit-too.html
    http://freetheanimal.com/2013/06/resistant-starch-now-we’re-getting-somewhere-part-2-35-links-to-research.html
     
    Last edited: Mar 13, 2014
  15. Valentijn

    Valentijn Activity Level: 3

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    I started VSL#3 a few days ago, so hopefully that will have an impact. It's got lots of Bifido and lactobacillus, as well as streptococcus thermophilus.
     
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  16. Firestormm

    Firestormm Guest

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    Hopefully you might, if the Lipkin Microbiome Study can proceed :)
     
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  17. xchocoholic

    xchocoholic Senior Member

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    The last time I looked Vsl#3 had a great reputation. Hope it works for you. Tc .. x
     
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  18. snowathlete

    snowathlete

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    Interesting as my bifido was also zero when I had my stool test before taking abx. I am hoping to rerun the stool test this month as I am stopping the abx, and see where my gut flora now is. I've been supplementing bifido the whole time too.
     
    Last edited: Mar 13, 2014
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  19. xchocoholic

    xchocoholic Senior Member

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    Sorry. I tried reading the first link and he lost me again.

    I'm assuming he's getting beat up somewhere over his theory.

    I'll check the web for the facts. Maybe Mercola, etc have looked at this.

    Thanks for your time tho. Tc .. x
     
  20. Vegas

    Vegas Senior Member

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    I recognize these pathogens as being gram-negative, at least five of these. Two or Three are from the proteobacteria phylum. Some colonize the upper bowel, but most colonize in more anaerobic conditions.

    So there is an obvious overabundance of gram-negative pathogens and this would disproportionately affect the lower bowel, which is harder to modify. These gram-negative pathogens are of course notable for their endotoxin content and the effects of lipopolysaccharide in impacting innate immunity. Just as notable though, and not coincidentally I don’t think, is the under-representation of species, vital to maintaining intestinal integrity and the environmental conditions needed to sustain a specific Bifidobacterial species, as well as providing the counter-response to these gram-negative pathogens. The under-representation of species includes those species involved in butyrate and propionate synthesis, including Faecalibacterium prausnitzii, Roseburia intestinalis, and others. Low numbers of F. prausnitzi is a finding seen in certain inflammatory bowel conditions, including Crohn's and I find this notable in that it happens to be highly dependent on Bifidobacterial species. The dependence in propionate and butyrate species on Bifidobacterial species probably extends to many functions including acetate biosynthesis, which is significantly altered by oxidative conditions & lactate metabolism, and the production exopolysaccharides, which participate in mucosal energetics/integrity, have a bactericidal effect, nurtures the commensals, etc.


    The very significantly decreased total numbers of Bifidobacterial species is notable, but I think the specific organisms may be more important than numbers. While I didn’t see subspecies taxonomy, there is a conspicuous absence of B. bifidum, B. adolescentis, B. longum, and what was described as B. dentum, which may be an error with the intention to designate B. Dentium. While strain specificity would allow for more useful conclusions, I do see these as being strains that are highly intolerant to oxygen, especially if the B. longum species is subspecies longum. In my view, this is likely a consequence of a redox imbalance. The deficiency of these particular organisms is further significant because of their composition as part of the infant microbiota. I am by no means an expert on Crohn’s, inflammatory disease or ME/CFS, but I am seeing these associations across many inflammatory disease processes, including ME/CFS as well as a number of other notable findings like perturbations in the purine/pyrimidine metabolism and protein kinase phosphorylation. In my view this has the hallmark of a process mediated by gram-negative pathogens and a collateral scarcity of key SCFA producing commensal species and their interdependent relationship with Bifidobacterial organisms, which have special roles, and happen to be among those species most intolerant to oxygen.

    While I think it is clear there will be major microbiomic differences between other disease processes and ME/CFS, including, for example, something like the overabundance of sulfate reducing bacteria in ME/CFS, it does seem the conditions for inflammation are starting to point to this combination of gram-negative pathogens and a lack of butyrate-synthesizing clostridial species. The evidence for a scarcity of particular species of highly anaerobic Bifidobacteria is weaker, but there have been few studies, if any, looking at a subspecies level. Much more study is obviously needed. I've also been watching a lot of money on Wall Street moving in this direction..
     
    Last edited: Mar 13, 2014

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