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Culturing of ‘unculturable’ human microbiota reveals novel taxa and extensive sporulation

Discussion in 'The Gut: De Meirleir & Maes; H2S; Leaky Gut' started by alicec, May 9, 2016.

  1. alicec

    alicec Senior Member

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    http://www.nature.com/nature/journal/vaop/ncurrent/full/nature17645.html

    Culturing of ‘unculturable’ human microbiota reveals novel taxa and extensive sporulation
    Hilary P. Browne,1, * Samuel C. Forster,1, 2, 3, * Blessing O. Anonye,1, Nitin Kumar,1, B. Anne Neville,1, Mark D. Stares,1, David Goulding4, & Trevor D. Lawley1,
    Journal name Nature Year published: (2016)
    DOI: doi:10.1038/nature17645 Received 25 September 2015 Accepted 08 March 2016
    Published online 04 May 2016

     
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  2. alicec

    alicec Senior Member

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    I found this yesterday while looking for something else. Then coincidentally last night I heard one of the authors interviewed on an Australian radio program.

    I got quite excited reading the paper and this was only reinforced when I heard Sam Forster say they have all these spores stored in their freezer and within a few years he could see them becoming the basis for new generation probiotics that would replace FMT in recolonising damaged guts (well that is my paraphrase, I can't remember exactly what he said).

    This work is the type of breakthrough we need to translate the explosion of new information on the gut microbiota derived from DNA sequencing into treatments that can make a real difference.

    There are two things of significance.

    First they have found ways of culturing many of these previously unculturable anaerobes. This means they can be thoroughly studied and their function better understood.

    Even more importantly, in finding that many of them can be induced to form spores, they have found a way around the limitations of current probiotics.

    Apart from the fact that current probiotic species don't in any way reflect the species actually in the gut, they do not colonise it either. Their benefit appears to derive almost entirely from modulation of the host immune system as they transit through.

    Spores are a way in which bacteria survive removal from a beneficial environment, a kind of dormant state, which enables the organism to survive for an enormously long time until it again encounters a suitable environment for growth.

    So now we have stable forms of many of the dominant gut bacteria (plus others we know little about) which could form the basis for future probiotics , along with ways of studying them so we can determine which are the critical core that might be able to repair damaged guts.

    This could well lead to the kind of tailored probiotics that we really need, rather than the hit and miss alternative of FMT.
     
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  3. Richard7

    Richard7 Senior Member

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    Scientifically this should be fascinating, but I wonder about making these things into pills.

    I recently read this interview with Jorge Frias-Lopez where he explains that what matters when looking at the ecosystem of a dental plaque is the genes that the bacteria have the potential to express. Because when the environment changes bacteria that had being commensal or beneficial can change in to pathogens if they have the genes to do so. http://www.nidcr.nih.gov/ScienceSpo...ral-microbiome-genomics-and-periodontitis.htm

    This is obviously a potential weakness in FMT.

    FMT's strength, when compared to normal probiotic supplementation is that they disrupt the existing ecosystem by washing most of it away and then implant a whole healthy ecosystem, and repeat this several times.

    When you adding or a couple of dozen species by taking a pill they are much less likely to find ecological niches. They are much less likely to survive in the gut.

    I would think that they are also much more likely to behave unexpectedly when you are throwing them into an entirely new environment. I would expect that they would be much more likely to either switch on pathogenic genes or to cause existing bacteria to do the same.

    This could also happen with FMT, each person is a new environment. Each diet is a new environment. Maybe There would be a problem, but at least we know that we have a gang of microbes that can play nice. And have presumably upregulated and down regulated the genes necessary for this to be so.

    I don't know that this would be the case in a probiotic pill.

    If this was very carefully researched before being made into a pill, with every microbe being tested for potentially pathogenic genes, it could be great. But I kind of expect that we will get a lot of shoddy supplements that are over hyped and could be dangerous.

    Sort of like all of medicine there I guess.
     
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  4. Richard7

    Richard7 Senior Member

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    Oh and I should add i have used, and continue to use probiotics. I am using oral ones at the moment.

    But I have reacted badly to some of them and have been glad that they were not spore forming and unlikely to last long in my gut.
     
  5. alicec

    alicec Senior Member

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    That is all just assumption. We don't know because we have never been able to study it.

    The study has developed at least some of the tools to enable us to do just that.

    I think we will be well able to pick out the charlatans. There are also plenty of dedicated scientists and clinicians out there who truly want to come up with better solutions. I for one am very willing to urge them on.
     
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  6. Richard7

    Richard7 Senior Member

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    Alicec, I want to see the science done too. I just have these moments, like when I read the interview I linked to above where I get a sense of how much there is to know before we can be sure that we are intervening safely.

    And how vastly oversimplified and misleading much of the information I have read (or heard from my doctors) has been and how dodgy the interventions I have taken have been.

    re this point
    I understand the first half of my statement to be true. I am not an ecologist and have no training in it. But my understanding is that when a new animal or plant is introduced to an intact ecosystem the general rule is that it won't find a niche and become established.

    There are exceptions, in New Zealand there were no plants that were good at colonising recently disturbed ground until blackberries were introduced. But I have only heard of it because I listened to a talk on the radio where an ecologist presented it as an exception.

    I have read the case of the rabbit in Australia being presented as more usual. There were two or three unsuccessful attempts to introduce it into a reasonably intact ecosystem and then when it was introduced to a massively degraded ecosystem there was an overly successful one.

    But have heard more than one ecologist state that a handful of bears or some other sort of animal being let loose in a foreign ecosystem will, even if they survive for a generation or two, most likely soon die out.

    I have read of practitioners having issues trying to introduce beneficial bacteria to their patients guts, and have myself being such a patient.

    So I do indeed assume that this is the case. Am I wrong? I mean wrong about the theory, no one knows about the practice as there is none yet.



    For the second part, sure I do not know what the case is. We won't know until the experiment is done. That is kind of why I am expressing doubts rather than making statements.

    But in that article that I linked to there is a section before the interview which starts with a quote from Philip Marsh

    And from the interview with Jorge Frias-Lopez
    Obviously they are speaking of disturbances in the ecosystem initiated by a pathogen.

    Which is kind of what we are talking about with FMT. I do not know the details, but I understand that for FMT they use some medical intervention or other to stop inflammation in the gut, wash it out then apply the sample of a healthy microbiome.

    Not asserting, just hypothesising, but would this not mean from the microbes points of view they were going from a healthy gut to a seemingly healthy gut. So they would be less likely, I once again hypothesise, to start producing those virulence factors or putative virulence factors mentioned by Frias-Lopez.

    I was kind assuming that the pill would be assumedly commensal or beneficial bacteria dropped into a diseased gut. That it would be just like the probiotics I have taken. And that if we did not fully understand them, which seems to be the case with stuff on the market now, and the assumption that they were certainly commensal or beneficial proved to be wrong etc etc etc.

    I do not mean to be all doom and gloom. One could presumably do the science and do it properly and all would be great. It is just that that article made an impression on me, and I have being thinking of some of the risks I took without knowing them to be risks when I listened to doctors and microbiologists and biochemists who were very certain that they knew what they were doing.

    I don't mean to be doom and gloom but maybe I'm having one of those days. Perhaps all these points are irrelevant and I should say I cannot wait till the research is done, and someone has written a book or an article about it that is accessible and not too simplified or too wrong. That too is an assumption, of course, and one I assume I would like to put to the test.
     

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