Articles

Probiotics

The Wall Street Journal has an assessment of Probiotics in the Jan 13, 2009 issue entitled Bug Crazy: Assessing the Benefits of Probiotics (1). For some reason when I wander around the hospital on rounds people show me articles such as this and ask, so whatcha think about this?

Probiotics are interesting. They are live bacteria given to treat and prevent diseases. It is one of those overlap areas for scientific medicine and so called alternative medicine. There are good clinical trials to suggest areas where these agents are of benefit, but other aspects of their use are blown out of proportion for the real or imagined benefit probiotics may provide. Much of alternative medicine where it overlaps with real medicine is the art of making therapeutic mountains out of clinical molehills.

The Wall Street Journal article is the kind of reporting that drives. me. nuts. It drive me nuts because the reporting acts as if the underlying assumptions of the therapies are true.

Start with the second sentence.

“Many medical experts believe that consuming healthy bacteria, called probiotics, improves the body’s overall balance of good versus bad micro-organisms, boosting general health.”

Many? What is many? A few loudmouths like me? A consensus? Experts in what? What is a healthy bacteria? Are the bacteria healthy? Or does it make you healthy? Then the last part of sentence, “improves the body’s overall balance of good versus bad micro-organisms, boosting general health.” What the does that mean?

Already these is the assumption, unchallenged, that there is an issue in people between good and bad bacteria that is affecting health. And which people? Which bacteria? Under what circumstances? The importance of understanding which patient populations may benefit from an intervention is key.

My mind was boggled when they mentioned that there were 241 probiotics released last year containing probiotics. Someone is getting a good balance of good income vrs bad income, boosting some bank accounts health.

Before we move on to the rest of the Wall Street Journal, lets talk colon and the bacteria that live there.

Your colon is a rich, complicated ecosystem. Each and everyone of you has a metaphorical rainforest in your colon. Your colon is a complex environment containing hundreds of species of bacteria, 99.9% of which are anaerobes (bacteria that are killed by oxygen). Each gram (2) of stool, and a gram is not all that heavy, has 10^11 anaerobes. That is one hundred billion organism per gram of poo. This may surprise you, but your colon is not a particularly hospitable place, and there is not a lot of oxygen there. As a result, organisms that thrive in an oxygen low or deficient place, anaerobes and microaerophilic organisms, predominate in your colon. The predominant anaerobes are bacteroides species. Aerobes, ie oxygen requiring organisms like E. coli, make up only 0.1% of your stool, or 10^5 to 10^7 per gram of stool. Thats 10 thousand to ten million aerobes per gram.

And thats the bacteria we can culture. It is estimated that we cannot grow about 80% of the bacterial species in the feces.

Bowel mucosa is inhabited by Bifidobacteriumand  Lactobacillus, the two most common bacteria in probiotics. These bacteria are minor constituents of the bowel flora, but since they live on the mucosa, along with  Eubacterium, and Propionibacterium, they may have more beneficial effects. The female genital tract does have a Lactobacilluspredominant flora. The Lactobacillus community varies from person to person. Lactobacillus crispatus and Lactobacillus jensenii are the lactobacilli that predominate in the vagina. The Lactobacillus you eat is not the Lactobacillus that is part of your normal bacterial flora.

The normal gut bacterial flora is important in many ways.

Micro-organisms block out potential pathogens. There are a limited number of niches in which bacteria can live. If the niches are filled with non pathogenic bacteria, then there is no place for pathogens to get a toe hold to grow. Over growth syndromes are a common complication of antibiotics and are frequently mistaken for a weakening of the host immune system. Wipe out the some or all of the normal bacteria, free up some ecological niches, and and bacteria or yeast not killed by the antibiotics will grow like blackberry bushes after a logging. Wipe out normal bacteria with antibiotics and get an overgrowth with yeast or Clostridium difficile, a particularly nasty form of infectious diarrhea. The immune system has not been compromised by the antibiotics, it is a result of the opening up of new living space for micro-organisms that were previously outcompeted for space.

Normal microbiologic flora is important if for no other reason that it fills up a space that could be used by more pathogenic organisms.

Micro-organisms do more than fill up a space. Bacteria, good bad and indifferent are more than animate place holders. They have been co-evolving with us for somewhere between six thousand and 6 million years. Genetic analysis shows that H. Pylori came out of Africa with us 60,000 years ago and head lice have been with us and our ancestors for 1.6 million years. None of us are truly alone, and, after death, will be consumed by the microbiology we have carried with us since the beginning of human existence. Introducing new strains of probiotics is akin to planting corn in a rain forrest. You may get some benefit, but do not think you are reconstituting the normal ecosystem.

During our co-evolution, bacteria have picked up some of the biochemical slack: micro-organisms make Vitamin K help with the digestion and absorption of food. Most importantly, at least from the perspective of my 11 year old, bacteria are responsible for most of the gas of flatulence. Disturbing the normal flora with antibiotics or illness or surgery or probiotics can lead to a variety of biochemical dysfunctions.

I mention all this so there is context as we explore the biologic plausibility and clinical utility of probiotics .

The reason d’etre for probiotics is inherently questionable: Normal bacteria gone, depleted, tuckered out? Take some extra bacteria and replete your ecosystem.   Compared to the complexity of the GI micro environment, probiotics contain just a few bacteria, and not even the most common bowel organisms. It is safe to say that the “good’  bacteria so highly touted in probiotics are but a minor constituent of a complex flora.

Some further fine points about the probiotics
- Lactobacillus in yogurt in not necessarily lactobacillus usually found in probiotic pills. Yogurt is usually L. acidophylis or Lactobacillus bulgaricus. The yogurt bacteria turn sugar to lactic acid, making the milk curdle turning it into yogurt. The lactobacillus in probiotics contain one of more Lactobacillus casei, Lactobacillus plantarum, Lactobacillus reuteri , Lactobacillus rhamnosus, or Lactobacillus GG. As mentioned, these are not the Lactobacill found in humans.
-The Bifidobacterium found in probiotics are not necessarily the Bifidobacterium found in and on you. There are many strains of Bifidobacterium, only a fraction of which are included in probiotics.
- Saccharomyces boulardii, found in some probiotics, is not a normal part of your flora.
- Typical of the unregulated supplement industry, what is on the label may not be in the bottle of probiotic pills. In several studies that have compared what is on the label with what is actually grown, not only were the organisms misidentified, sometimes the bacteria were dead were dead. Organisms not mentioned on the label, like enterococcus, were sometimes isolated. But then enterococcus is a real constituent of the gi tract.
- Probiotics, not being part of the normal flora, are cleared and cannot be isolated soon after stopping eating the probiotic. They are not normal flora and will not persist unless you keep consuming them.
If you are worried about your normal gut bacteria, be reassured. We are always consuming fecal flora in the food you eat and the water you drink. The food, your spouse, and the world, is covered in a thin patina of gastrointestinal bacteria, so you are always repleting your bacterial flora orally. Bon appetite. Families tend have similar bacterial strains. My gut flora more closely resemble my parents than my wife’s, suggesting there may be a genetic predisposition for which strains of bacteria make up your gut.
When you give probiotics to normal humans you are introducing, relative to the number and quantity of bacteria that are already there, a small amount of foreign bacteria. Continuing our metaphor, it is like trying to put a putting green in an Amazonian rain forrest. For normal people, it makes no microbiologic sense to take probiotics.
“For maximum benefit, scientists say, try to consume a variety of different bacteria, as each may contribute something slightly different.”Your best bet, with this reasoning, would be to eat a variety of human stool. That way you will get many different bacteria, all contributing something slightly different. “Probiotics are defined as “live micro-organisms which when administered in adequate amounts confer a health benefit,” according to 2002 guidelines developed by the World Health Organization and the United Nations. Exactly how this works isn’t fully understood, but scientists believe that good types of bacteria have long lived in symbiosis with humans and that the positive health effects may have evolved over time.”
Thats right. So why take large amounts of foreign  bacteria and yeast that are not a normal part of your gastrointestinal flora?
“In choosing a probiotic, consumers should look for products that list a specific strain of bacteria on their label or on a Web site. Look for three names — in Lactobacillus rhamnosus GG, for example, the final two letters identify the strain. The GG strain has been well tested scientifically and has shown health benefits. A product that simply uses the first two names may include a similar, but not identical, bacterium that doesn’t have the same science behind it.”
Health benefits is so non specific. There is science behind probiotics, but is it good science? My bias: at baseline in normal people, the colon has a enough bacteria and, like supplements, does not need extra bacteria. The alleged health benefits of probiotics are often an example of spin.
Per the WSJ, probiotics are helpful for the following. I will give the WSJ credit where credit is due, they make a point of mentioning that most of the studies that show benefit are funded by the makers of the probiotic, although they do not mention explicitly that studies show the source of funding biases clinical studies in favor of the funder.
1) Gut health. What is gut health? It sound good, doesn’t it?. How can you argue against health? Many supplements promote some kind of health. Gut health, vaginal health, immune health, etc. I have zero idea what this means. Water promotes health. Steak can promote health. Wine promotes health. Everything that is not poison can, under the right circumstances, be said to promote health. It is a content free statement.
2) Increased digestion. This manifests by increased transit time. “…the company says a recent study, presented at a conference of the American College of Gastroenterology, found that a dairy drink with the same active ingredients as a four-ounce container of Yo-Plus reduced transit time to 21 hours from 31 hours.”
This is good because? There is a myth that the colon is filled with toxins that need to be eliminated. Not true to my knowledge. Why might ingesting a large bolus of foreign bacteria lead to increased transit time? Though most of human history, food poisoning was common. Eating tainted food was an unfortunate byproduct of no refrigeration or food preservation combined with starvation level existence. There are three major ways people acquire infections: sex, inhalation and eating.  Through most of human history the food supply was not clean, so it is not surprising that a large part of the immune system lines the gut.
According to Dannon, 70% of your immune system is in the gut.  True enough. It prevents the normal flora from getting into the bloodstream (a huge problem in people whose immune system is depressed from chemotherapy) and provides the first line of defense against ingested bacteria and toxins. If you inadvertently eat a large amount of bacteria, be it contaminated food or probiotic yogurt, the body gets rid of it with increased transit time. If you really want to increase transit time, take a probiotic laced with Salmonella. That is probably why you get increased transient time with probiotics: the normal inflammatory response attempting to rid the body of a bolus of foreign bacteria. Spin. Take an unimportant and perhaps normal physiologic response to infection and make it a benefit.
3) Irritable Bowel Syndrome. The clinical trials do suggest benefit from various probiotic formulations for the symptoms of IBS. Curiously, there are numerous studies to suggest that IBS is a sequela of infectious diarrhea’s of all etiologies. It is interesting that adding back a bacteria would help symptoms, although what the best probiotic formulation to treat IBS is not known. Since IBS is a post infectious disease, one would wonder if normal people took large quantities of probiotics for a long period of time it would cause IBS. My first prediction for probiotics: long term use in normal people will lead to increased risk of IBS.
4) Colic. Reasonable data to suggest that colic is improved with probiotics. If colic is due to a alterations in bowel flora, then they may be benefit from probiotics. The big benefit from probiotics, as mentioned, is probably by blocking pathogenetic bacteria. Bacteria do not just float free in the colon. The have ecologic niches and often have to bind to specific sites on cells. Probiotics probably have their benefit by blocking the site where the more pathogenic organisms bind, if that is the cause of colic. Most parents with a colicky would do ANYTHING legal to quiet their baby and get just one good night of sleep, so I hope this one study is confirmed.
5) Immune health. More spin. The woo meisters usually phrase it as “boosting the immune system.” First, the immune system in normal people does not need boosting. It is fine at baseline, and millions of years of evolution have given us what is presumably an optimal immunologic set point. When we are infected we respond with inflammation, and inflammation is not always good.

What about boosting or strengthening the immune system.

The data is contradictory. Some probiotic effects, such as on inflammatory bowel disease, are supposed to be due to decreasing immune function by depressing cyokines, while other effects are supposed to be due to increasing immune function in increasing local antibody production and T cells. There are in vitro (test tube), animal, and human studies that show wide ranging effects of probiotics on the immune system. Guess what? That is what is supposed to happen. Any time you take in large quantities of a living organism that is not part of your normal flora, the immune system is going to take notice and react. What they call boosting or increasing immune health, I call inflammation.

I am going to limit discussion to the DanActive product by Dannon with the bacteria Lactobacillus casei. They have trademarked the name of their strain, Lactobacillus casei Immunitas. TM.

Each bottle of DanActive has 10 billion live bacteria, so from a bacterial colony count, it is like eating a gram of stool. So what does that do for your immune system. Not much. They make a big deal about immune strengthening, but the supporting data they provide in their slick but almost substance free scientific summary for providers is as follows (from the Dannon web site).

1) “Consumption of yogurt containing L. casei Immunitas (TM) during 30 days resulted in a significant increase in the percentage of children with a concentration of Lactobacillus greater than 6 log10cfu/g of feces. “

That must have been fun to collect. Children taking DanActive for thirty days increasingly have lactobacillus in their stool. Why is this good? Because they say so. They say it is regulating normal bowel flora. No they are not. Taking a complex ecosystem and trying to replace it with a monoculture of “good” bacteria.

2) L. casei Immunitas (TM) stimulated DNA synthesis and cAMP (cyclic AMP) production in cultured IEC-6 (intestinal epithelial cell line) cells, indicating increased proliferation and cell activity. Again. Why is this good? Any bacteria not part of the normal flora will cause an inflammatory response. Causing an immunologic response is how the immune system is supposed to respond to everything that is not you. Extrapolating from a typical test tube response to improving immune function in people is quite s stretch.

3) “DanActive (TM) may modulate the innate immune cellular response, by reducing the depression of natural killer (NK) cell concentration, induced during intense physical exercise.”

So what. That’s enhancing the immune system? The study to demonstrate this earth shattering immune enhancement?

They looked at 13 parameters in 25 athletes whose NK cells decreased with exercise. First they took milk for a month, then Lactobacillus for an month and found one parameter that decreased less after taking Lactobacillus for a month: NK cells. Milk had a 5 % decrease in NK cells after exercise and lactobacillus had a 3 % decrease. Whoa. No controls (each patient served as their own control) I’m convinced. This is the basis of the immune enhancement of Danactive. The result in one of 13 parameters is probably random noise.

If you do a Pubmed search on L. casei and other lactobacillus you can find a variety of effects on immune function.  Various immunomodulatory effects are reported.

Now here is the secret: flood any animal with any organisms and you will get the same response. For example, the literature on Candida, more of a pathogen. If you expose animals or cells in culture to Candida you get immunomodulation. You can activate or turn off the immune system, depending on which part of the immune system you are measuring and what pathogen you are testing.

If the organism, be it Candida or Lactobacillus, induces an inflammatory response, you can protect animals from subsequent infection and from cancer.  If you prime the immune system before hand, you get a better host response to subsequent infection. This is a nonspecific response to all foreign bacteria, including probiotics.

More spin. Calling the normal response to pathogens (or to relative non pathogens in the case of Lactobacillus) an immune enhancement rather than inflammation is clever advertising, as is making the result seem like something special rather than the same old inflammatory response the immune system has to all foreign organisms.

There is an interesting literature on the consequences on chronic inflammation and vascular disease: the NEJM had a recent article on how chronic periodontitis leads to endothelial cell activation (the cells that line your arteries) and may account for the long known association between periodontitis and heart attacks. The cardiology literature is filled with epidemiologic studies correlating chronic inflammation and heart attacks.

Acute infections are a prothrombotic states: if you have an acute infection the inflammatory state increases your risk of clot formation and increases your risk for heart attack, stroke, and pulmonary embolism. That risk is increased for up to a year after an infection,

Inflammation, which is what taking 10 billion extra bacteria should cause, may not not be such a good idea.

The other interesting feature of infections is that after inflammation comes anti-inflammation. For every action there is an opposite and sometimes excessive reaction as the body tries to get back to baseline equilibrium. Patients with severe infections, if they survive the acute disease, are at increased risk of acquiring a new infection in the month after the infection is cured as the anti-inflammation phase increases the risk for another infection.

I will make two more predictions about taking chronic probiotics.

a) Population studies will show an increased risk of heart attack, strokes, and pulmonary embolism as a consequence of the mild increase in the inflammatory state induced by chronic probiotics.

b) Infections will increase in the month or two after stopping chronic probiotics.

Any budding epidemiologist out there feel free to run with these ideas.

6) Antibiotic-associated diarrhea. Here is where probiotics have the best data to support their yse. I think the data is clear that they are effective in preventing antibiotic associated diarrhea. So much so that at several of my hospitals we give live yogurt to normal patients who get antibiotics. Probiotics for the treatment of diarrhea? I am not so sure. The data is not as compelling and the treatment is potentially more risky.

Complications from probiotics are rare and may be more common when being used to treat an acute inflammatory diarrhea. If you have a bacillary diarrhea like C. difficile or Shigella or E. coli you can get an impressively inflamed colon. Intact bowel is an important barrier to infection, just like intact skin. Most people would be disinclined to rub large numbers of living bacteria or yeast on a raw, oozing, macerated wound. One would think this is a bad idea and could give the micro-organisms access to the blood stream.

That is what has happens with probiotics. You immune system recognizes most of your bacterial flora, so it is rare to get bloodstream infections from normal flora during infectious colitis. You do not have that innate immunity against the bacteria in probiotics. Almost all the fungemias due to S. boulardii occur when given to treat an inflammatory diarrhea. While it is very rare, if you give people a large oral bolus of live bacteria to which they have no existing immunity and their gut looks like the colonic equivalent of bad road rash, expect the occasional organism in the blood stream. This should come as no surprise to anyone in ID. If you give normal animals a large oral inoculation of some relatively non pathogenic organism it can overwhelm local defenses and lead to a blood stream infection in the absence of colitis.

My career is based on treating weird bugs, so I have a bias against possibly giving a patient an infection they don’t already have. I have seen 2 cases of S. boulardii fungemia in patients receiving this yeast to treat C. difficile. The medical literature does not indicate an increased bacteremia from Lactobacillus due to the use of probiotics. Population studies do not find an increase of Lactobacillus in the blood, but there are a few case reports of people with either severe mechanical or immunologic problems taking probiotics and getting Lactobacillus in the blood stream, for example an AIDS patient with lymphoma. Taking large amounts of a live bacteria in the immuno-incompetent may not be the best idea.
Probiotics are useful for the prevention of antibiotic associated diarrhea. Probiotics may be helpful in preventing other overgrowth syndromes or diseases associated, perhaps, with perturbations of the gut microbial flora such as IBS and colic.
Probiotics are foreign bacteria that are not a normal part of your gi tract, they do not enhance or immune system and, in normal people to note promote the nebulous bowel health.
If you are a normal human, with a normal diet, save your money. Probiotics have nothing to offer but an increased cost.
——

(1)http://online.wsj.com/article/SB123180831081775767.html

(2)  For you metrically challanged, one teaspoon is about five grams and I found out that the US dollar bill weighs about a gram. So imagine a dollars sized smear of poo. There are 100 billion bacteria in it.

Posted in: Basic Science, Science and Medicine, Science and the Media

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26 thoughts on “Probiotics

  1. storkdok says:

    Thank you for this article. My GI doc has recommended probiotics for me for Crohn’s Dz. From my literature search, there isn’t conclusive evidence that probiotics helps the IBD, but it looks promising. What is your take on the use for IBDs? I have a major migraine right now, so I hope I phrased this in a lucid way.

  2. MedsVsTherapy says:

    THanks for taking the time to write this up. Relatively easy to read, and chock full of info.

    The “enhance immune function” claim is about as frequent as the “increase blood flow” claim.

    Many altmed interventions are claimed to either “enhance immune function,” or “increase blood flow.” I just don’t buy these claims of support for whatever (magnets for pain and healing, etc.) I always wonder: doesn’t our body finely regulate blood flow anyway? Doesn’t our body have a decent immune system anyway?

    As far as I can see, these processes can be upset in people with some specific, bad condition. Ischemia happens. But for the rest of us, “increasing blood flow” to our knees, brain, or wherever is probably, if anything, a bad thing.

    Nonetheless, if you slap either one of these claims, or both, on any altmed product, you can guarantee sales.

  3. MedsVsTherapy says:

    I still have this lingering suspicion that bowel transit time has some big effect on health. I suspect that there is an optimal time – not to fast, and not too slow. My reasoning is this: there are many things that are suspected to be preventive of heart disease or cancer. These pop up as significant in observational studies, but then in the more focused clinical studies (in vitro, cultures, clinical trials, etc.), they do not pan out. This is what seems to be happening for lycopene/tomato sauce (“especially cooked”), circumin, vegetables, red wine, anti-oxidants, and other suspected ingredients.

    My thought is that these components may be associated with lower cancer or heart disease by the association with yet another factor: decent meals. There is little-to-no fast food or convenience food with circumin. If someone gets circumin, they are probably having an old-fashioned Indian mom set a decent Indian meal in front of them.

    If an Indian is not eating circumin, they are probably eating fast food and/or conveneicne food.

    Generally, the fast foods/convenience foods will make your bowel transit time be slower. Meat, fat, cheese, bleached flour, and absence of soluble fiber.

    So, that is my pet theory of why circumin is truly associated with lower cancer rates, by observational data, (there also happens to be some bench science type evidence, such as promotion of development of blood vessels, but isn’t that bad when it comes to cancer?), but has not clearly emerged in trials. Same with antioxindants. If you are eating lots of blueberries, chances are you are eating a more balanced diet, with deecnt bowel transit time, versus a convenience/fast food diet, which generally has components that elad to slower bowel transit time.

    This is totally a hypothesis that seems to fit a range of actual phenomena. I am not making any claims. So, feel free to comment on my gut-related idea. The discussion of bowel tranist time prompted the idea to write my crazy hypothesis.

  4. Fifi says:

    More interesting, to me, is the relationship of the bowels to emotions and also having found that there are some of the same “neuro”-chemicals and chemical receptors in the bowels (cannabinoids and serotonin). I suspect this will be an, ahem, fertile area of research. Particularly vis a vis conditions like IBS and depression.

  5. Fifi says:

    And, yes, eating lots of blueberries will speed up bowel transit time! (Too many may well do so to an undesirable point!)

  6. Fifi says:

    That said, the “bowel transit time” theory seems rather silly to me (and is sold by the poo enthusiasts of CAM who love looking at poo). Voiding too fast is a huge problem too so it’s really about not being constipated or having the runs. I’d suggest most people in North America get constipated more often due to dehydration than what they eat (though obviously eating things that are low in moisture and fibre contribute to constipation, as do diuretic drinks such as coffee and sodas).

  7. Thank you for this posting, Mark. For several years I’ve been annoyed by the “probiotics” hype and had, on the way back burner, an eventual plan to write a debunking. Much better for a bonafide ID expert to do that. “Planting corn in a rain forest” is the perfect analogy. Also, regarding this right-on description:

    “Much of alternative medicine where it overlaps with real medicine is the art of making therapeutic mountains out of clinical molehills,” I can’t help but plug my definition of “CAM”:

    “A spectrum of implausible beliefs and claims about health and disease. These range from the untestable and absurd to the possible but not very intriguing. In all cases the enthusiasm of advocates vastly exceeds the scientific promise.”– http://www.sciencebasedmedicine.org/?p=62

    This sort of thing has also led some mostly OK academics to feed at the Woo trough: here is Sherwood Gorbach, recipient of the “Alexander Fleming Award for Lifetime Achievement in 2007 by the Infectious Diseases Society of America,” whom I remember as one of my better teachers in medical school, snuggling up to Rep. Dan Burton, “Quackery’s best friend in congress”:

    http://bulk.resource.org/gpo.gov/hearings/107h/77497.txt

    In that testimony Gorbach, who had patented a “probiotic” in 1985, uses bait and switch and grovels before Burton by spouting obsequious, anti-science propaganda such as:

    “[NIH] review panels just don’t believe in anything that isn’t straight party-line conventional therapy.” Say it ain’t so, Sherwood!

    Two minor points:

    1. Somewhere in the last few years I read a report in which many samples of “probiotics” purchased in well-known health food stores were found to contain no viable organisms, or organisms of different species from what was named on the label. If true, it shows that objections to the non-regulation of herbal “remedy”-packaging also apply to “probiotics.”

    2. Does “anaerobes” necessarily mean “killed by oxygen?” I think it just means “able to thrive in the absence of oxygen.” “Obligate anaerobes” can’t use oxygen for metabolism at all; “facultative anaerobes,” such as yeast, can. I realize that many obligate anaerobes are inhibited by oxygen, but I don’t think all are. There are also shades of oxygen inhibition: H. pylori prefers 5% oxygen over a petri dish, but won’t grow in 21% (present in air). I know you know these things, but it’s worth clarifying for the non-biology-maven reader cohort.

  8. daedalus2u says:

    The regulation of inflammation in the gut is complex. There is excellent data that infestation with parasitic worms reduces the symptoms of Crohn’s disease.

    http://gut.bmj.com/cgi/content/full/54/1/87

    Not strictly an infection because the species used does not colonize humans.

    Probiotics are a subject near and dear to me, I am working with commensal bacteria but ones that live on the skin, not in the gut. The specific ones I am working with are ammonia oxidizing bacteria, they oxidize ammonia into nitrite, the first step in the process of nitrification. They are obligate autotrophs, so they are not culturable with traditional infectious disease techniques. The don’t grow on any media used to isolate pathogens, and with a doubling time of 10 hours, they are very slow to culture.

    They do suppress other surface bacteria, through inhibition of quorum sensing and blocking the formation of biofilms.

  9. Fifi says:

    daedalus – I agree that the research into the positive role parasites can play is very interesting!

  10. StuV says:

    Nitpick:

    10^5 to 10^7 per gram of stool. Thats 10 thousand to ten million aerobes per gram.

    Methinks you’re missing a 0 there.

  11. Dave Ruddell says:

    All this talk of poo reminds me of one of my favourite infomercial salesmen, Dr. Michael Ho! Here is the link to his Ab-Trimmer (warning, there’s sound, so you may want to turn your speakers down):

    http://www.abtrimmer.com

    The video at the site is pretty good, but to get a full appreciation for it, you really have to see the full infomercial. Mind you, the end of the short video does implore you to “Join the Doctor Ho movement”, so it does retain the best line.

  12. Mark,

    Oops. You made the point about the labeling not always matching the contents, but in my initial skimming of your post I missed it. Sorry about that.

    KA

  13. FINE, Mark, you’ve convinced me that fecal transplants are a good idea after all. ARE YOU HAPPY?????

    ;)

  14. psamathos says:

    What about “prebiotics”? Those aren’t bacteria, I know, but it seems to be a new buzzword picked up by cheese and yoghurt manufacturers recently. From what I can tell it’s just fibre.

  15. Jules says:

    @ Meds:

    Bowel transit time is ~24 hours in humans, and 12 hours in cats. Much longer and much shorter, and you’ve got problems. Most of the absorption of nutrients takes place in your duodenum, anyway–the other 21 feet of gut are really just to make sure nothing gets left behind. And okay, your colon for the vitamin K.

    (As for how I know it’s 12 hours in cats: my cats get fed every 12 hours, on average, which coincides remarkably well with their litter box usage).

    Can I say that I find it delightfully ironic that there’s this whole movement that encourages swallowing bugs by the bucket, but eating something off the floor is still considered disgusting? :-)

  16. DLC says:

    I smelled something funny about “Danactive” when they announced it contained a bacteria with a name ending in (sounds like) immunity. Never having heard of such a bacteria before didn’t help their case. Now I see it was Lactobacillus renamed.
    They’re going a long way just to sell some sour milk.

  17. lisa millington says:

    There is a western world pandemic of food related problems.

    Its a serious problem that needs strong leadership and voice to speak out thats not driven by money to come out and say to people what should we be eating and not eating and how we should live and what to expect from ourselves both physically and mentally.

    As humans we are simply not suited to the way are living, hence why are bodies and minds are becoming more stressed, with added toxins from the environment and food etc etc. The sooner someone comes out with clear messages and answers there is always going to be doubts and ongoing discussions, on what pills to take and what not to take, which ultimatley costs jo public money.

    As humans we are all different but food , probitoics, toxins waste, pollutants etc etc etc are the same ………..
    People become desperate for solutions and want answers, they are vunerable and feel alone………People are suffering and dying.

    Who out there is going to take on this massive task…………We would think twice to put man on the moon but in and hundred years time after several generations of people suffering we will have a human fit enough to go back.

  18. Fifi says:

    lisa – There’s a global “pandemic” (though that’s not really a great word to use here) of food related problems throughout the world – the most severe and ubiquitious being starvation leading to disease, disability and death.

    People in affluent “western” countries have been told how to stay healthy continually but choose not to because they prefer to indulge than restrict/moderate. (In Canada we have the long-running Participaction program, which is also tied into phys-ed in elementary schools.) There are plenty of answers, people just don’t like them and ignore them in favor of illusive and illusory magical solutions that promise eternal life and happiness (aka fairytales).

    Lisa – there are lots of religions that would be happy to tell you how to eat and live, that dictate rather than inform. It’s what SCAM really is – a set of faith based beliefs that sets out to dictate how people eat and live (well, it sets out to make money by dictating to people how to eat and live based upon ideology not medicine).

  19. Fifi says:

    Lisa – “People become desperate for solutions and want answers, they are vunerable and feel alone………People are suffering and dying.”

    And people are being conned by those who are willing to lie about having easy solutions because they don’t like the work/effort and self honesty required to make lifestyle changes. That’s why SCAM bases itself on pseudoscience and is religion masquerading as medicine, and goes after people suffering from chronic diseases, because people are desperate and ready to be conned since they’re afraid and can’t accept that we don’t know everything.

    Lisa – “Who out there is going to take on this massive task…………We would think twice to put man on the moon but in and hundred years time after several generations of people suffering we will have a human fit enough to go back.”

    Lots of people today are fit. In fact, today’s athletes are fitter than any time previously in history due to our increasingly sophisticated understanding of the body. America’s biggest problem is the idea that it’s someone else’s responsibility to manage one’s body and life. It’s not like TV, books and the media aren’t full of a million different ways to get in shape. There are certainly cultural, sociological and biological issues related to obesity and obesity related diseases – but ultimately self responsibility is required if one wants to change *anything* in one’s life (though external support and peer pressure certainly helps).

  20. Kikki says:

    Saccharomyces boyardii???

    S. bouraddii???

    If you are to criticize it, at least call it by its real name: Saccharomyces boulardii

  21. Mark Crislip says:

    argh. I cannot spell a single bug I kill for a living
    I ran it though my spell checker and they were not flagged.
    anyone know a good mac medical spell checker?

  22. nitpicking says:

    Up next: an article on entomophagy!

  23. Kikki says:

    Saccharomyces boulardii effects on gastrointestinal diseases
    (“Current Issues in Molecular Biology”)

    http://www.horizonpress.com/cimb/v/v11/47.pdf

    Abstract

    “Health benefits attributed to probiotics have been described for decades. They include the treatment and the prevention of gastrointestinal diseases, vaginal and urinary infections and allergies. Saccharomyces boulardii, a species of yeast widely distributed, has been described as a biotherapeutic agent since several clinical trials displayed its beneficial effects in the prevention and the treatment of intestinal infections and in the maintenance of inflammatory bowel disease. All these diseases are characterized by acute diarrhoea. Administration of the yeast in combination or not with an antibiotherapy has shown to decrease significantly the duration and the frequency of diarrhoea. Experimental studies elucidated partially the molecular mechanisms triggered to improve the host health. The discovery of its anti-inflammatory and immuno-modulatory activities in correlation with the advances in the understanding of mucosal immunology opens a new field of perspectives in S. boulardii therapeutic applications.”

  24. Heh– I thought Mark was just making a joke at the expense of Chef Boyardee food products!

  25. khan says:

    So is it OK that I eat a bit of yogurt almost every day?

  26. Pman says:

    Great double-blinded placebo controlled prospective trial, certified by my gastroenterologist academic mentor @ UNC.

    Needs to be replicated on a larger scale, but guys – this stuff works. Don’t take too long to jump on board!

    Effect of a probiotic preparation (VSL#3) on induction and maintenance of remission in children with ulcerative colitis.

    Miele E, Pascarella F, Giannetti E, Quaglietta L, Baldassano RN, Staiano A.
    Department of Pediatrics, University of Naples “Federico II”, Naples, Italy.
    OBJECTIVES: Several probiotic compounds have shown promise in the therapy of ulcerative colitis (UC). However, a strong sustained benefit remains to be seen. Uncontrolled pilot studies suggest that a probiotic preparation (VSL#3) maintains remission in mild to moderate UC and reduces active inflammation in adult patients. Aims of our prospective, 1-year, placebo-controlled, double-blind study were to assess the efficacy of VSL#3 on induction and maintenance of remission and to evaluate the safety and tolerability of the probiotic preparation therapy in children with active UC. METHODS: A total of 29 consecutive patients (mean age: 9.8 years; range: 1.7-16.1 years; female/male: 13/16) with newly diagnosed UC were randomized to receive either VSL#3 (weight-based dose, range: 450-1,800 billion bacteria/day; n=14) or an identical placebo (n=15) in conjunction with concomitant steroid induction and mesalamine maintenance treatment. Children were prospectively evaluated at four time points: within 1 month, 2 months, 6 months, and 1 year after diagnosis or at the time of relapse. Lichtiger colitis activity index and a physician’s global assessment were used to measure disease activity. At baseline, within 6 months and 12 months or at the time of relapse, all patients were assessed endoscopically and histologically. RESULTS: All 29 patients responded to the inflammatory bowel disease (IBD) induction therapy. Remission was achieved in 13 patients (92.8%) treated with VSL#3 and IBD therapy and in 4 patients (36.4%) treated with placebo and IBD therapy (P<0.001). Overall, 3 of 14 (21.4%) patients treated with VSL#3 and IBD therapy and 11 of 15 (73.3%) patients treated with placebo and IBD therapy relapsed within 1 year of follow-up (P=0.014; RR=0.32; CI=0.025-0.773; NNT=2). All 3 patients treated with VSL#3 and 6 of 11 (54.5%) patients treated with placebo relapsed within 6 months of diagnosis. At 6 months, 12 months, or at time of relapse, endoscopic and histological scores were significantly lower in the VSL#3 group than in the placebo group (P<0.05). There were no biochemical or clinical adverse events related to VSL#3. CONCLUSIONS: This is the first pediatric, randomized, placebo-controlled trial that suggests the efficacy and safety of a highly concentrated mixture of probiotic bacterial strains (VSL#3) in active UC and demonstrates its role in maintenance of remission.

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