A research paper in this week's Nature shows a major advance in the study of the role of the human gut flora in disease and health. Metagenomics of the Human Intestinal Tract (MetaHIT) Consortium examined the role of gut flora in health by a massive project (ref. below) to determine the DNA base sequence of the majority of the millions of genes in the thousands of species of bacteria that abide in human feces. Gut flora have been linked to many human diseases, as well as the normal function of the human immune system.
Major Findings:
- 576.7 gigabases sequenced (150 times larger than human genome)
- Identified 3.3 million gut flora genes
- Represents more than 1,000 bacterial species
- Each individual harbors approx. 160 different species
- Most prevalent species are identified and shared by everyone
Feces from 124 Europeans
Feces samples (124 individuals total) from a Danish project to determine the role of gut flora in obesity and from a Spanish project to determine the role of gut flora in Crohn’s disease and ulcerative colitis, were extracted for total DNA.
Illumina Multiplex Sequencing of PCR Amplified Fragments
DNA samples from each individual were fragments (<800 bp) and amplified to include indexing information and sequencing primers. The sequences of a dozen of the fragments at a time was determined using a dozen different dyes (Illumina multiplexing). Sample preparation and analysis was fully automated to permit identification of overlapping contiguous sequences and assembly of bacterial genomes (1,000-1,150 most common). The sequence data in this study represents most of the bacterial species of the gut.
Comparison to 89 Existing Human Gut Bacteria Genome Sequences
The new study represented more than 200 times the sequence information than in all previous studies combined. Existing genome sequences could be identified among the bacterial genomes assembled from the new data. The identified and sequenced bacterial species represent approximately a tenth of the common bacteria in the gut.
Polysaccharide/sugar Metabolism Common among Gut Flora
Genes coding for enzymes needed to metabolize pectin, sorbitol, mannose, fructose, cellulose and sucrose, were common among the gut flora. Bacteriophages were also significantly (5%) represented in the total gut metagenome. Most of the genes were assigned recognizable bacterial functions, but many genes, presumably involved in interactions among the bacterial community or in modification of gut function have not been characterized.
Obese, Crohn’s Disease, Ulcerative Colitis, Compared to Healthy
The bacterial gene compostion of individuals diagnosed with Crohn’s Disease and ulcerative colitis were different and distinct from healthy individuals. Individuals with Crohn’s disease had 25% fewer species of gut flora than comparable healthy controls.
This study demonstrates the feasibility of using current techniques to examine in detail the interactions between gut flora and tissues of the gut that are involved in health and disease. This also suggests the risks of antibiotics in altering critical functions of the gut flora, as well as the alteration of gut flora to support health and cure disease.
reference:
Junjie Qin, et al. 2010. A human gut microbial gene catalogue
established by metagenomic sequencing. Nature 464, 59-65.
26 comments:
does bentonite clay have a role to play in the struggle with biofilms?
Dr Ayers. Is there an optimal probiotic to take? I know that probiotics have different strains of bacteria in them. Is it more important to have a large variety of strains, or is it better to focus on just a few strains but in large amounts?
Hi Dr. Ayers,
Just wondering if you caught wind of this one: http://www.sciencemag.org/cgi/content/abstract/sci;science.1179721v1
http://futurity.org/top-stories/are-belly-bacteria-making-us-overeat/
They did post more detail in a separate section:
http://www.sciencemag.org/cgi/content/full/science.1179721/DC1
which reveals the high fat diet is:
http://www.taconic.com/user-assets/Documents/Taconic_D12492.pdf
while the low-fat is:
http://www.labdiet.com/pdf/5001.pdf
I think Peter (hyperlipid) has mentioned that high fat and high sugar can be quite damaging to the liver. I wonder how this plays into it. Obviously the higher fat diet was tastier (lard). I wouldn't necessarily label this as "saturated fat" since monounsaturated fat makes up the majority of lard.
This study finds soluble fiber enhances immunity and reduces inflammation in mice, but the authors don't mention (at least not in this news blurb) fiber's impact on gut flora as a possible contributing mechanism:
http://www.lef.org/newsletter/2010/0309_Soluble-Fiber-Improves-Immune-Function.htm?source=eNewsLetter2010Wk11-1&key=Archive
I'd be interested to see the full text when available.
Dr. Ayers, I'm a big fan of your blog. Would saccharomyces boulardii and mannanOligoSaccharides be a good probiotic supplement? If not what would you recommend? I know this is not medical advice. Thanks,
Dr,
I am sorry to write you abouit it here but I didn't find any other closer topic. Dr, People who believe they have an intestinal candidiasis have seen some interesting white mucus formations in their bowel movements. (there are some pictures in Curezone candida forum) Many people believe it is candida itself but I have read from some Drs and microbiologists candida only can be seen under a microscopy, even in its yeast or fungal hyphal form. Please, I have defended the Drs information against the general opinions. I would like you clarify me about it to be sure that candida can not be seen in stool without a microscopy.
Anonymous,
Yeasts are larger than bacteria and about the same size as human cells. All of these cells are microscopic. You can't see blood cells without a microscope.
At the same time, if you pack the cells together, e.g. packed red blood cells, liver, mushrooms or the "curds" in exclusively breast fed baby stools, you can see human/fungal/bacterial cells. I have even precipitated viruses in large enough quantities to see clumps.
Yeast clumps are easy to see in the mouths of babies with thrush. Clumps of bacteria can be seen on infected tonsils.
White masses in stools can easily be checked to see if they are yeast, by just using a microscope. The rest of the stool should be mostly packed bacteria, if the gut flora are healthy and are digesting fiber.
Thanks for the question.
Dr,
Thanks for your always quick explanation. I have learned a lot about biofims reading your materials, and I now think those white mucous formations people see in stool are Candida Biofilms or microbial biofilms. People pass those formations only after antifungal therapies. By the way, I have read that candida biofilms are different from bacterial biofilms. The matrix in those candida biofilms are mainly glucose. I have also read from medical papers that Fatty Acid can disrupt them. Undecenoic Acid has shown to disrupt Candida Albicans biofilms. No all candida strains have matrix with the same substances. What do you think???
Thanks Prof. Art
Jorge
Jorge,
Biofilm matrices are complex and diverse, but have many similarities. They seem to mimic the matrices of the host, i.e. acidic polysaccharides crosslinked by divalent cations, e.g. calcium, magnesium, zinc. Proteins of the microbial inhabitants of the biofilms attach to the matrix and the attachments have a significant hydrophobic component. That is why PEG destabilizes biofilms.
Biofilms are essential for normal gut flora and the biofilm environment is needed to stimulate the exchange of genes within the gut flora to produce new bacterial species that provide a part of the diversity of the gut flora. Biofilms aid in adaptation of the gut flora to diet.
If fatty acids destabilize biofilms, which would be expected by the fact that fatty acids function as soaps and biofilms are held together by hydrophobic interactions, then what about the detergents that we eat? A common detergent in tooth pastes is SDS. SDS is very effective in attacking biofilms and should be effective against dental biofilms, but what is the impact on the stomach and intestines?
I think that attacking biofilms should be restricting to periodic stripping of biofilms to avoid long term shifts to pathogenesis, but I worry that we don't have good sources of healthy gut flora to provide for a reestablishment of a better replacement.
The appendix also provides a starter kit for reestablishing gut flora, so stripping away problematic gut flora may then result in just a return to the same problem. There is no point to stripping away the gut flora unless a new diet selects for and supports a new gut flora.
Thanks for your comments/questions.
Hi Dr. Ayers,
A study of interest:
http://neuroanthropology.net/2010/08/04/whats-in-your-gut-termites-for-example/
Thanks for the great blog.
Dimitri,
That is a great article that shows that people and termites probably get their gut flora from the same place, i.e. the bacteria growing on the plants that they eat. People eating algae end up with genes from bacteria that grow on the algae, and people who eat plants in Africa end up with genes from bacteria that grow on those plants. Algae-eating fish probably also have gut flora that can digest algae polysaccharides.
The point is that gut bacteria are produced in the gut by the exchange of genes between resident bacteria and bacteria in the diet. Biofilms cause the induction of genes for DNA exchange. Researchers are trying to find the bacteria that colonize the guts of nursing babies, but don't realize that the genes are present in other species and are transferred into adult bacteria that are present to create the baby species. It is also likely that bacteria capable of digesting critical milk oligosaccharides are also present on or in the mother's breasts.
Thanks for the stimulating input.
Hi.
First of all, i wanna thank you for the information you provide, i've spent some time and read all the post&comments on this blog. Found a lot of interesting stuff here.
Since i have UC (ulcerative - hemoragic rectocolitis) and also a combined undifferentiated spondyloarthropathy (and some arnold's neuralgia that seems to come from the spondy part) i was familliar with the no starch diet from other sources - Elaine's Gottschall SCD diet, A. Ebringer's Low Starch Diet and so on.
So your information makes a lot of sense to me and also filled some gaps.
I was diagnosed in my late 20's (now I'm 31) following a long habbit of eating a lot of inflamatorry food (high refined carbs, corn oil and so on). Also immune disease have a history onto my family - cousins, my father.
I tried to add some of your advices into my lifestille. I've started with Cod oil, probiotics&vit D and some new foods that i avoided untill now - apples & leaks. Found some supplements rich in innulin and pectins and also reintroduced coffee.
Strange as it may sound i started flaring from those changes - until then my diet wich is 100% following the principles you stated kept both my UC and my USPA under controll.
Yougurt - homemade, using bifidus essensis as starters - also seems to trigger flares. So i am under the susspicion that probiotics are the main problem here. Strange as they were suppose to help...
I am giving you a link with the probiotics prospect i am using, as a information:
http://www.jarrow.com/product.php?prodid=227
I choosed it because i've read several abstracts over the internet regarding L. Rhamnosus and it's role in inducing&mantaining remission in UC.
I know that you've confirmed that you have little information about HOW to change gut flora, but i support your theory - based on the reactions i've had on several food&diet stiles - that changing it seems the right way to ease an inflammatory process.
PS. Sorry for my english, it's not my native language.
Alin, Romania.
Dr. Ayers,
Wondering if you are familiar with the work of Chris Masterjohn. About a month ago, I read an interesting piece from him essentially discussing EPA toxicity. I am a young (33 yo) male recently diagnosed with Crohn’s. For years I have followed a healthy diet, similar to the one you suggest, along with higher dose fish oil (~1 gm of EPA+DHA/day). My only symptoms are loose stools and weight loss. All my lab work is excellent and I was only diagnosed with crohn’s due to a capsule endoscopy that showed multiple ulcerations thru out my small bowel. Thinking thru the pharmacology of fish oil has led me to believe that mechanistically, its effects are similar in many ways to the effects of NSAIDs. It’s well documented that the use of NSAIDs can cause not only stomach ulcerations, but also small bowel ulcerations. About 3 weeks ago, I stopped taking fish oil and have noticed ongoing improvements in my loose stool. Curious to your thoughts on this and the work of Chris Masterjohn (see the article below).
http://www.westonaprice.org/know-your-fats/2021-precious-yet-perilous.html
Ryan,
I just reread the Masterjohn review of essential fatty acids (omega 3&6). Since it is based on the same literature that I am also summarizing in my suggested anti-inflammatory diet, it is not surprising that we all come to essentially the same conclusions.
In the presence of existing inflammation, omega-3 fatty acids are converted into lipid peroxides. For this reason, people suffer from fatty liver should not be treated with fish oil. Alternatively, the peroxide formation can be avoided by feeding omega-3 fatty acids in the presence of saturated fats.
I suspect that if you observe more intestinal inflammation in the presence of fish oil, then your existing source of inflammation is producing lipid peroxides and fanning the flames. You need to be eating more saturated fats to benefit from the anti-inflammatory qualities of the omega-3s.
As you indicated in your parallels with NSAIDs, which block omega-6 derived prostaglandin production needed for gut development, your existing inflammation may be lowering the availablity of omega-6 fatty acids and under those conditions, the supplemented omega-3s may further reduce gut development and lead to leaky gut.
Those are my thoughts. Let me know if more saturated fats help.
thanks for the quick response. my intake of saturated fats is already pretty high. i use plenty of coconut oil, butter and ghee. my thinking is that the use of fish oil (in addition to a healthy diet) precipitated a deficiency of omega 6/AA leading to ulcers, compromised intestinal integrity (as you mentioned) and eventually diarrhea with malabsorption. i'm optimistic that stopping the fish oil (along with my current diet of high sat fats, fermented foods, kefir) will prove curative. i'll keep you posted. I might be an interesting case study if a repeat capsule endoscopy looks good. ...
Dr. Ayers
Some people recommend vitamin E to reduce the effects of lipid peroxidation when taking fish oil. Any thoughts on this?
Asim,
I think that lipid peroxidation and oxidative stress are very important and directly related to inflammation. I don't think that eating anti-oxidants is very significant unless they affect the major cellular anti-oxidant systems, e.g. vit.C, glutathione precursors, uric acid.
Most of the plant-anti-oxidants, phytochemicals, don't get out of the gut or past the liver. They are probably important for reasons other than their ability to interact with oxidants. Their chemical structures suggest that they may interfere with the binding of proteins to cellular receptors (but that may only be a consequence of my obsession with heparin-binding domains.)
The bottom line is that I don't think that taking vitamin E will make much difference on lipid peroxidation. Lowering overall oxidative stress by decreasing inflammation may be more important.
Thanks for the questions.
Hi Dr. Ayers,
Regarding vitamin E and fish oil, Dr. Ronald Krauss noted that fish oil when taken with vitamin E, does not work to reduce triglycerides. He explains the mechanism here in an article called "Hold the antioxidants and improve plasma lipids?"
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC398437/
What probably happens is that the antioxidants work to neutralize the highly unsaturated (easily peroxidized double bonds) in the stomach before they enter the liver. This makes them more stable, and there is no need to withhold them from circulation.
Peter, hyperlipid, posted about this a couple of years ago.
http://high-fat-nutrition.blogspot.com/search/label/AGE%20RAGE%20and%20ALE%20(8):%20VLDL%20degradation%20and%20Krauss
personally this makes me think that fish oil SHOULD be taken with antioxidants, if we are interested in the benefits of omega-3 fatty acids, but not the peroxidation that comes with them (which coincidentally LOOKS like it fixes high triglycerides). It could also be that fish oil in it's highly reactive form acts as a stressor that itself has a cascade effect that leads to improved health.
Or, incorporating my reasoning above, it could be both at the same time--so reducing the peroxidation potential with vitamin E would lessen the harm of intaking such fragile and dangerous unsaturated fats.
In summary, there IS a direct cause and effect between fish oil with antioxidants vs. fish oil without, or we wouldn't see the disparate effect on VLDL and triglycerides that we do in fact see.
Dr. Ayers,
Was my post on LDN deleted by accident? It talked about beta endorphins and autoimmune diseases such as Chrohn's and Multiple sclerosis. Perhaps it is more appropriate in the autoimmune disease posts? I can repost if it was deleted in error.
Hi,
would antiinflammatories slow wound healing? I am a competitive athlete and I just received a cortisone injection earlier today. Would this possibly be hampering my ability to recover?
Hello Art!
You wrote:
"Most of the plant-anti-oxidants, phytochemicals, don't get out of the gut or past the liver. They are probably important for reasons other than their ability to interact with oxidants."
That seems to be the case. Have you thought or read what happens to phytochemicals in the gut (even to most complex ones like ellagitannins)? Pretty interesting stuff.
mtflight,
The articles that you cite are highly provocative.
I have posted some comments on low dose Naltrexone and have recommended to a relative to support therapy for bladder cancer. I think that LDN should be examined for its potential impact on a wide range of diseases. The endorphin/opioid connection is poorly understood and also impacts acupuncture.
The hot/cold sensors that are triggered by topical applications of capsaicin, menthol and castor oil, also inhibit inflammation. I think that these effects are also mediated by endorphins and this may indicate that the LDN is working via suppression of inflammation/NFkB signalling.
The action of vitamin E, polyunsaturated fats and lipid receptors and the role of AGE/RAGE requires a huge expanse of cell biology to explain. I have written articles on AGE and have done experiments modeling RAGE interaction with molecules that inhibit heparin-protein interactions. The sensitivity of receptors to glycation is fascinating, because the specific molecular targets are frequently heparin binding domains. Heparin binding protects against glycation and heparin synthesis genes are shut down by NFkB signalling/inflammation.
As I said, this area is very intertwined and it makes my head swim to read these articles. Thanks.
mtflight--would you please re-post the LDN link ? Thanks.
Tanya,
There are also several articles on LDN in Wikipedia.
Here is mtflight's post. (I think that the spam filter kicked it out, because it had active links.)
This message is for Ryan, but possibly useful to all, particularly anyone with autoimmune disease or cancer.
There's a hypothesis that autoimmune diseases, notably multiple sclerosis and chrohn's disease are the result of an under-active immune system. Said deficiency is with beta-endorphins.
Here is a hypothesis paper, explaining the possible mechanisms involved:
http://www.ncbi.nlm.nih.gov/pubmed/19041189
In a nutshell, by blocking the endorphin receptors for a few hours (with an FDA drug that's approved for addiction to opioids called Naltrexone, except at a < 1/10 dose, dubbed low-dose naltrexone, or LDN). In response to the endorphin blockade, the body up-regulates beta endorphin production and the expression of the endorphin receptors as well, resulting in a cascade effect that ultimately has had positive health effects in many.
Here's the Chrohn's disease paper:
"Low-dose naltrexone therapy improves active Crohn's disease"
http://www.ncbi.nlm.nih.gov/pubmed/17222320
I'm personally taking it for Hashimoto's thyroiditis, and in two months have reduced my T4 prescription by 25%. There's anectodal accounts in the forums/groups devoted to this subject.
My prescription comes from a doctor who has had much success with a handful of MS patients.
Dr. Ayers, it would be great to get your opinion on the subject and its mechanism.
Cheers to good health!
Thanks Dr Art. I have read and posted about LDN before here, but wanted to see what others had found.
I got labs back today...vit D at 66 after several months of 15K units daily. Calcium at 9.1. HDL is up from 50 to 56. CRP has almost tripled to 3.8. Aches are returning and hormones still not right. Diet has been less than optimum but that is a necessary evil of life right now.
Still keeping the faith and hoping for an answer or a doc that will test something that will lead us down a right path. LDN would be my choice but know of no one who would prescribe it, esp. with no 'diagnosis'.
Merry Christmas!
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