What to Do About Antibiotic Resistance? Improve Immune Function

I recently got a flyer from my HMO. “Feel better soon . . . without antibiotics!” said the front page. “Antibiotics do not kill viruses” said the second page. Apparently the point of the flyer is to reduce antibiotic usage. I am surprised that doctors need protection from patients asking for antibiotics for viral diseases.

Antibiotic resistance is a problem, yes, but the bigger problem is how those who run our health care system ignore the immune system. Here are examples:

1. The historical solution to the problem of antibiotic resistance has been to develop new antibiotics. The problem has not stimulated research into how to strengthen the immune system. Here is a 1992 editorial in Science: “Mechanisms such as antibiotic control programs, better hygiene [= more handwashing], and synthesis of agents with improved antimicrobial activity need to be adopted in order to limit bacterial resistance.” Nothing about improving immune function. A 2012 World Health Organization report about the problem does not contain the word immune.

2. The idiocy of tonsillectomies. Forty years after researchers figured out that tonsils are part of the immune system, tonsillectomies remain common. Removing tonsils because of too many infections makes as much sense as removing part of the brain because of memory loss. I have never encountered a doctor who appears to understand this.

3. Epidemiologists have yet to systematically study what makes the immune system more or less powerful. For example, this epidemiology textbook does not contain the word immune. Nor does this review of 25 epidemiology textbooks.

4. A respected professor of pharmacology at the University College London named David Colquhoun left the following comment on this blog: “Talking of made up theories, the corniest of all has to be “stimulating the immune system”. There is [not], and never has been, any evidence that it happens — it is the eternal mantra of every quack who is trying to sell you their own brand of implausible therapy.” Here is an example of the evidence he says doesn’t exist. Professor Colquhoun is a Fellow of the Royal Society.

5. I know very little about the immune system. I barely know what a T cell is. My job (psychology professor) has nothing to do with it. Yet I have come up with three ideas related to it: 1. Tonsillectomies are idiotic. 2. We need regular intake of microbes to be healthy — in part to stimulate the immune system. 3. We need exposure in small amounts to the germs around us for our immune systems to best protect us. (So it’s not obvious that outside of hospitals more handwashing is a good thing.) Only because these ideas are obvious (#1 and #3) or semi-obvious (#2) was someone as ignorant as me able to think of them. That one ignorant outsider thought of three of these things before the hundreds of thousands of health researchers did suggests how little they think about the immune system.

Someday the people in charge of our health care — or the rest of us, ignoring them — will figure out how to make our immune systems work much better. We will sleep much better, eat much more fermented foods, take enough Vitamin D at the right time of day, and so on. Perhaps we will wash our hands less and kiss more. Antibiotic usage will go way down, selection for resistant microbes will become much less intense, and antibiotic-resistant microbes will become much less common. The problem will disappear.

31 Responses to “What to Do About Antibiotic Resistance? Improve Immune Function”

  1. Mike Says:

    A while back I went to a doctor because I had a persistent sore throat and some other symptoms and he did a bunch of other tests first.

    Me: “What about my sore throat.”
    Doc: “I’m not concerned. It just looks like a virus.”
    Me: “OK, but it’s been sore for over a month now.”
    Doc: “I can prescribe you an antibiotic.”
    Me: “Antibiotics don’t do anything to viruses.”
    Doc: “Correct.”
    Me: “…”
    Doc: “…”
    Me: “…”
    Doc: “We could do an allergy panel.”
    Me: “No thanks.”

  2. Koanic Says:

    The Antiseptic Baby and the Prophylactic [1] Pup
    Were playing in the garden when the Bunny gamboled up;
    They looked upon the Creature with a loathing undisguised; —
    It wasn’t Disinfected and it wasn’t Sterilized.

    They said it was a Microbe and a Hotbed of Disease;
    They steamed it in a vapor of a thousand-odd degrees;
    They froze it in a freezer that was cold as Banished Hope
    And washed it in permanganate [2] with carbolated soap [3].

    In sulphurated hydrogen [4] they steeped its wiggly ears;
    They trimmed its frisky whiskers with a pair of hard-boiled shears;
    They donned their rubber mittens and they took it by the hand
    And ‘lected [5] it a member of the Fumigated Band.

    There’s not a Micrococcus [6] in the garden where they play;
    They bathe in pure iodoform [7] a dozen times a day;
    And each imbibes his rations from a Hygienic Cup –
    The Bunny and the Baby and the Prophylactic Pup.

    – by Arthur Guiterman

  3. Nancy Lebovitz Says:

    One way that the medical profession doesn’t respect the immune system– hospitals tend to be bad about interrupting patients’ sleep.

    Seth: yes, very good point.

  4. Tuck Says:

    “Someday the people in charge of our health care — or the rest of us, ignoring them…”

    I’ll go with the latter scenario. We recently had a bit of a battle with our pediatrician over how to handle a fever. She just had no clue that fever is a first line of defense against infection… If you read the literature, which I did, you can pretty quickly ascertain that “treating” a fever leads to worse outcomes, while letting it run leads to better outcomes (survival is better, in my book).

    I even found an amusing study, basically a letter to the pediatric profession, noting that parents were alarmed by fever in direct relation to their time spent with a medical professional. The letter concluded that pediatricians ought to do a better job of conveying correct information to their patients.

    Obviously our doctor hadn’t gotten the memo. And I think she’s a good doctor, she’s just hobbled by a bad education (Harvard Med, as I recall…).

    After chastising us for not treating the fever with Motrin (I refused) she sent us an alarmed text telling us *not* to use Motrin, as the illness likely had a hemorragic component, which the Motrin would make worse.

    The kid recovered nicely with essentially no treatment whatsoever, but a healthy paleo diet and lots of sunshine…

    (Interestingly, I had her sit out in the sun for a bit to generate some Vit. D, and her fever promptly skyrocketed. Cause and effect?)

  5. Rich Says:

    It’s funny, I was watching The Brady Bunch with my 9 yr old yesterday where Mrs. Brady and Cindy both get their tonsils out because they were getting periodic sore throats and the sniffles.

  6. peter Says:

    http://www.lowdosenaltrexone.org/

    since i’ve been taking low dose naltrexone (about 3-4 years) i’ve had one cold.

  7. Walter Says:

    Seth,

    Given I have no tonsils would you add anything to your list of suggestions?
    Thanks,

    Walter

    Seth: Sue the doctor who removed them.

  8. Patti Says:

    Tuck you are very lucky your child was okay. Yes although fever is the first line of defense it is also the first sign the body is out of homeostasis. Fevers in children can be very dangerous due to their unpredictability.

    Nancy Lebovitz. I agree with you 100%.

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  10. chris Says:

    Hey Seth,

    A few problems with your post. I’ll organize them by point.

    1. Researchers would love to stimulate the immune system, however, that is not a reason to forgo antibiotics. Antibiotics save lives, and even in non-fatal diseases can greatly increase quality of life. The immune system is incredibly complex and difficult to try to regulate from the outside, so progress is very slow on that front. Also, increasing your immune system (whatever that means exactly? More T cells, B cells, cytokines, better complement response, etc? You would need to specify what you mean by that first and foremost) response has nothing to do with bacterial resistance to antibiotics, so it is not surprising that it wasn’t included in the editorial you link to. Bacterial resistance is a competition between bacteria and antibiotics, not our immune system. Sure, a better (still too vague) immune system would help resistance to any disease, but we don’t have good data on exactly how to do that yet (from what I currently understand).

    2. Tonsillectomies. You are absolutely right than an abuse of tonsillectomies would be idiotic. However, the current guidelines (seen here from the Mayo clinic http://www.mayoclinic.com/health/tonsillectomy/MY00132/DSECTION=why-its-done) only call for the procedure in the case of severe recurrent infections and other complications (basically if your tonsil keeps getting infected, the immune system there isn’t doing its job and the risks are outweighing the benefits of keeping that tonsil).

    Seth: Sounds tautological (“if the risks are outweighing the benefits”).

    3. Before that question could even start to be addressed you would have to explain what exactly constitutes a “more powerful” immune system. Otherwise what do you study? Give a phone survey asking how powerful someone thinks their immune system is?

    Seth: The more powerful your immune system, the fewer colds you get and the shorter time they last. That’s one way to measure immune function.

    4. What I think the professor was referring to is the incredible overuse of the term “stimulating the immune system” by quacks who simply use it as a way to claim that all modern medicine is a waste of time. That is very different than the article you linked to that gives a specific mechanism, specifically showing how a vitamin D deficiency could limit immune system function.

    5. Conventional medicine does not ignore healthy habits that also support your immune system such as getting enough sleep, eating healthy, not being deficient in nutrients, etc. Also, your second and third points in point number 5 are based on conjecture, not hard evidence. I would recommend that you do a little more research into exactly what medical researchers and immunologists are doing before you assume you’ve come up with something that completely overturns a field. For example, if I thought I came up with a simple thought experiment that overturned special relativity, I would go educate myself more on the topic, maybe email an expert or two and ask their opinion before I posted my opinion on a blog saying I was smarter than a bunch of Ph.D. physicists. It is much more likely that I just don’t understand relativity than that I’ve disproved it.

    Seth: “I would recommend that you do a little more research into exactly what medical researchers and immunologist are doing.” You seem to be saying I have overlooked something that contradicts what I say here. What is it?

    Contrary to what you say, my second and third points in point number 5 are based on hard evidence, which you can find via the linked page and posts. I have posted twice about hard evidence for the third point (existence of an early warning system) and dozens of times about hard evidence for the second point (microbes in our food stimulate our immune system). The fact that you think “thought experiments” are involved supports my view that these ideas are remarkably obvious.

  11. Jaroslav Says:

    Early Exposure to Microbes Reduces Inflammation Related to Chronic Disease Later

    In my country (Czech Republic) we have a saying – or rather, used to have, as the hygienic and neurotic approach to raising children has caught up with us – that every child should eat a cart of dirt and cart of manure during childhood to be healthy.

  12. Adam Says:

    Chris said: “1. Researchers would love to stimulate the immune system, however, that is not a reason to forgo antibiotics. Antibiotics save lives, and even in non-fatal diseases can greatly increase quality of life. The immune system is incredibly complex and difficult to try to regulate from the outside, so progress is very slow on that front. Also, increasing your immune system (whatever that means exactly? More T cells, B cells, cytokines, better complement response, etc? You would need to specify what you mean by that first and foremost) response has nothing to do with bacterial resistance to antibiotics, so it is not surprising that it wasn’t included in the editorial you link to. Bacterial resistance is a competition between bacteria and antibiotics, not our immune system. Sure, a better (still too vague) immune system would help resistance to any disease, but we don’t have good data on exactly how to do that yet (from what I currently understand).”

    Seth’s point wasn’t that people that need antibiotics should forgo them, so you are attacking a Straw Man in the first part here. He also never said that antibiotics don’t save lives or that no one needs them.

    What I think he is trying to say is that the specialists are looking at a small part of a bigger picture, which is limiting the potential solutions they could come up with. The body isn’t a sterile environment where bacteria and antibiotics are interacting with each other alone. In many cases, people will recover even from bacterial illnesses all on their own, even without antibiotics. In some illnesses, antibiotics merely shorten the duration or intensity of the disease. In this sense, you can think of antibiotics as an aid to the immune system, not as a replacement for it and not separate from it.

    Your last point, that we don’t have a good idea about what boosts the immune system might be true for you specifically, but that doesn’t mean that information isn’t out there. There are several examples in this thread already. To add to them, there is some good data out there that zinc boosts the immune system. I recently read a study where they gave zinc to severely ill pediatrics and reduced the rate of antibiotic treatment failure by about 50%. Search PubMed for “2012 Lancet zinc” and I’m sure it’ll come up.

  13. Chris Says:

    Hello Seth and Adam,

    Thank you for your responses. I will try to clarify what I may have left too vague while trying to be brief.

    Seth,

    I don’t understand your tautological argument. All I am saying is that there are still situations today where tonsillectomies are a good procedure. Sometimes, the damage that can be done by leaving a tonsil outweighs the potential benefits of keeping that tonsil (cancer, severe recurrent painful infection, etc)

    I apologize for the tongue in cheek response about an immune survey. You can indeed measure components of the immune system in response to certain therapies. Maybe looking at cold rates would be beneficial for some studies, but not antibiotic resistance because the common cold is typically caused by rhinoviruses, not bacteria. Also, the amount of cofounding variables (including differential exposure to germs) in an epidemiological study would make it very difficult to justify creating an entirely new immune boosting treatment without a more controlled trial.

    About the field as a whole (and this should help to answer your questions too Adam), you are conflating infectious disease/microbiology with immunology. Yes, both components (the infecting microbe and the host immunity) are important, but they are so complex that two different fields currently deal with them. Antibiotic resistance is fundamentally a bacteria vs. antibiotic problem, our immune system is not really a part of it, outside of being part of the environment that the bacteria are trying to inhabit in your body. Yes, the antibiotic aids our immune system, but that is by killing off some of the bacterial population, not by “working together” in some way. The only difference between antibiotic resistant bacteria and susceptible bacteria is that one will not be killed by an antibiotic while it is infecting you. Your immune system does not influence bacteria susceptibility to that antibiotic, nor does the antibiotic boost your immunity.

    Therefore, to accuse infectious disease people about not studying the immune system is to accuse them of not doing someone else’s job. Immunologists are working on that, try searching for nature reviews of microbiology in Pubmed. You can find articles like this one (http://www.ncbi.nlm.nih.gov/pubmed/22113499) that involve immunologists looking at things like dietary components and their influence in innate immunity. However, the field is still in its infancy and nowhere near making good enough treatments to negate further antibiotic production. Still, contrary to your post, scientists are researching how to improve immunity. Immunologists are not all a bunch of dense scientists completely ignoring entire avenues of potential therapies.

  14. Chris Says:

    Adam,

    To clarify what appears to be a strawman:

    Seth asserts and implies in his post that research into antibiotics is unnecessary and that simply following his guidelines will make antibiotics obsolete. That to me implies that he thinks we should stop researching antibiotics.
    “Antibiotic usage will go way down, selection for resistant microbes will become much less intense, and antibiotic-resistant microbes will become much less common. The problem will disappear.”

    “Antibiotic resistance is a problem, yes, but the bigger problem is how those who run our health care system ignore the immune system. ” -not necessarily true… There are diseases out their that will still infect you no matter how strong your immune system is (MRSA, B. anthracis, tuberculosis, the list goes on) and that is what we need antibiotics for (and of course antivirals for the major viral diseases)

    I found what I think is your article in the Lancet (http://www.ncbi.nlm.nih.gov/pubmed/22656335). Some points: deficiency in many vitamins/minerals is known to affect your immune system, and the researchers didn’t measure pre-treatment zinc status. It could have been that all the subjects were zinc deficient, and that increasing their zinc levels brought their immune function back to normal (rather than boosting it). Also, what was considered a failed outcome of the study (death, intensive care, or a need to change antibiotics rapidly) has very little to do with antibiotic resistance (that is, the zinc supplementation does not change whether or not the infection was caused by a resistant microbe, which actually makes me wonder as to why they included that 3rd failed outcome). Finally, as the authors clearly state: zinc is an adjunct treatment, NOT a potential substitute for antibiotics.

    Please tell me if anything above is unclear, it is difficult to discuss studies in a medium as limited as blog comments.

  15. Chris Says:

    And in one more obnoxiously long blog comment, I will try to address your posts you link to in points 2 and 3 under point number 5:
    Your evidence for “we need to eat microbes” is weak overall and misleading in places. What can seem painfully obvious is often wrong in experiment. I will go through each of your points

    Point 1: We like umami, sour, complex flavors, etc. Another interesting theory is that we like spices in our foods because many extracts of spices contain antimicrobial compounds (allicin in garlic, this study on traditional Indian foods and Vibrio cholera http://www.ncbi.nlm.nih.gov/pubmed/21415500, onions, turmeric, etc, the list goes on and on). This would imply that it was better for us evolutionarily to ingest less microbes. Two competing thought experiments, no hard evidence either way. You need more than just that conjecture to prove that all microbe exposure is good for you.

    Seth: My theory is not “all microbe exposure is good for you.” It is that the microbe exposure we get from eating microbe-rich foods (e.g., fermented foods) is good for us. There’s a big difference. Why you keep talking about “thought experiments” puzzles me. That’s not where my data are from.

    Point 2: Food traditions. People fermented their food first and foremost to make it last longer, not for health benefits. There may be some benefit to eating fermented foods, no doubt, but claiming “genetic preference” for fermented foods is a stretch. Back in the day, you ate what was available, and if that was only fermented stored food, you would probably develop a taste for it.

    Seth: “People fermented their food first and foremost to make it last longer.” And you know this because . . . ?

    Point 3: Probiotics. I agree with probiotic use and definitely appreciate their therapeutic potential. That said, only certain species of microbes are beneficial in our guts (variants of E. coli, Lactobacillus, Bacteriodetes and Firmicutes families, etc). Probiotic benefits do not imply that you should just throw every microbe into your system that you can. If you throw the organism I do research on, Salmonella enterica, in your gut in the name of probiotics, you will be one very unhappy person for 7-14 days.

    Point 4: Fermented foods. See point 3. Certain microbes are great for you, certain microbial products are great for you, but NOT all of them. The details absolutely matter. Staph aureus’s toxin is also a microbial byproduct, just as much as lactic acid or propionic acid (propionic acid is what gives Swiss cheese its flavor).

    Seth: What does Staph aureus have to do with fermented food?

    Point 5: hormesis. None of your cited evidence has anything to do with bacteria or infectious microbes. The mechanisms by which radiation and other stressors may cause hormesis are very different from your immune system.

    Seth: Radiation hormesis involves intracellular repair systems. The immune system is another sort of repair system.

    Point 6: Bad effects of antibiotics. Are caused by a decrease in normal microbiota. Which would imply improvement by reintroducing the normal microbiota, NOT just any microbe randomly. Not just eating microbes. Still.

    Seth: I suggest that many (or all?) of the bacteria we need in our gut are found on the food we eat. When we eat food with lots of microbes, we are inevitably eating food with lots of bacteria specialized for that food. Not “random” microbes.

    Point 7: Hygiene hypothesis. Very interesting area of active research. Not a reason to just flood yourself with any microbe though. In case it is hidden behind a paywall, here is the conclusion of a recent review (on pubmed here http://www.ncbi.nlm.nih.gov/pubmed/22257145):

    “While it is clear that the microbiota significantly influences
    host immune maturation and immune activity, the molecular
    basis for these immunomodulatory mechanisms is only
    beginning to be elucidated. The presence of certain bacterial
    species or strains seems to be important, potentially because
    of direct interactions with the host (e.g., via PRR activation)
    or via their metabolic activity in vivo (e.g., SCFAs generation). Thus, care should be exercised in the selection of
    immunoregulatory microbes for administration in human
    studies as it is likely that not all microbes are equally effective and dietary factors may significantly influence the production of immunoregulatory metabolites. In addition,
    significant effort needs to be focused on the elucidation of
    the microbiota-associated molecular pathways that are
    impacted by dietary factors so that rationale prevention and
    treatment strategies can be formulated, which will include
    matching essential microbes and dietary components. Specific
    projects mining the microbiota for metabolites and ligands
    that modulate host immune function will likely lead to a new
    class of immunotherapeutic agents with relevance to a variety
    of inflammatory states, including allergy and asthma. Lastly,
    the hygiene hypothesis should now be updated to include dietary factors and the interaction of dietary factors with the
    microbiota.”

    Points 8-12 can all be explained with information above that discusses why fermented foods and certain probiotics can be good for you, so I will end here.

    In conclusion, I find no hard evidence for your point number two, at least in terms of the “just eat plenty of dirt and/or microbes and you’re set”. There is evidence that specific microbes at specific times can have great benefits to patients, but what you advocate is a huge overgeneralization and could potentially lead some of your readers to put themselves at more risk of disease than they should be.

  16. Adam Says:

    Chris, it sounds like you are a microbiologist? If so, you must be aware that there are both Bacteriocidal and Bacteriostatic antibiotics. As the name suggests, some of these drugs KILL bacteria and some just prevent them from multiplying. If there is not an interaction between the immune system, the bacteria and the antibiotic, how is it that Bacteriostatic antibiotics are effective in treating bacterial infections? It seems to me that Bacteriostatic agents slow the bacteria down enough that the immune system itself can eliminate the bacteria successfully.

    I don’t really get your distinction between bringing an impaired immune system back up to normal function and boosting the immune system. It seems like you think the immune system is always running at 100%, except in rare cases. Do we even have a good definition of what 100% is? How do we quantify it? To me, it seems much more likely that most people’s immune systems are somewhere between 0 and 100% of their potential, maybe on a sort of Bell Curve. It isn’t hard to imagine that there are a variety of interventions that could move one toward the right (toward 100%).

  17. Cliff Clayton Says:

    As a fellow non immunologist, I refer everyone to the Jaminet’s Perfect Health Diet. They recommend Potassium Iodide.

    This may not be an example of immune boosting but I will take it. I have suffered from chronic sinus infections most all my life (58 I am). I have slowly worked my dosage up to 8 mg/day over the course of 4 months. I now have free breathing through both nostrils most of the time instead of seldom if ever. I sleep better. No sinus pressure/headache. This must be how most people breath. Amazing.

  18. Chris Says:

    Hey Adam,

    Yes, as you stated, bacteriostatic antibiotics do exist, and their mechanism of action is to prevent bacterial growth without killing them (although the line is a bit blurry, because many bacteriostatic compounds become bactericidal at a higher concentration). So yes, they would ideally hold the bacterial population in stasis while your immune system acted to kill them off. However, the key distinction is that the antibiotic is still not interacting with your immune system, it is just slowing bacterial growth giving your immune system time to respond. The same immune response would happen without the antibiotic, but the bacteria would have had more time to multiply and cause a more severe disease without the antibiotic. A stronger immune system won’t make the bacteria more or less susceptible to the drug, and is therefore not an acceptable answer for the problem of bacterial antibiotic resistance. It will help you clear any infection more quickly (if it is an infection that your body is able to handle, for those it can’t you’d better hope you have some antibiotics available), so it may make the drug APPEAR more effective, but it is still a completely separate entity.

    I think I may be coming off a little unclear on my overall point, so let me clarify. A stronger immune system is a great thing, there are whole branches of immunology focused on defining exactly what a strong immune system is and figuring out how we can make our immune systems better. That said, it is an extremely complex process that on this blog is erroneously depicted as being extremely simple and withheld from the public because all immunologists are supposedly a bunch of morons. That’s what I have an issue with, because it is simply not true. The medical establishment is not ignoring the fact that our immune system is an incredibly important tool and many researchers are actively trying to improve it. The author of the blog is falsely depicting himself as smarter than an entire field of medicine, while acknowledging that he barely knows a T cell from a B cell. That just ain’t right.

    Seth: You write: “it is an extremely complex process that on this blog is erroneously depicted as being extremely simple and withheld from the public because all immunologists are supposedly a bunch of morons.” That is far from what I wrote. One of my points is that there are simple helpful things that can be said about the immune system (e.g., the existence of an early warning system) that have not been said by insiders. That is not the same as saying the immune system is “extremely simple” or “all immunologists are . . . a bunch of morons”. You have ignored my broad point that the problem of antibiotic resistance can likely be solved by improving immune function. Another simple idea I haven’t heard from insiders.

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  20. andrew Says:

    He isn’t saying he is smarter only that the incentive structure of doctors and researchers is not aligned with patients very well.

    The point is pay attention to your daily routine and make small changes is a good strategy for staying healthy.

  21. Jill Says:

    @Chris, my take on what Seth was saying re: antibiotic-resistant bacteria and stronger immune system is this:
    If people generally had stronger immune systems, antibiotic use would probably decrease, thereby reducing the process by which bacteria become antibiotic-resistant (and out-compete the nonresistant strains).

    I don’t think he was trying to say that a stronger immune system will modify the response of resistant bacteria to the antibiotics they are resistant to.

    Seth: That’s right, thanks.

  22. Chris Says:

    Tried to respond to respond to Andrew and Jill a few days ago but the internet was eating my comments. I’ll just skip that for now and go back to Seth’s.

    ” It is that the microbe exposure we get from eating microbe-rich foods (e.g., fermented foods) is good for us.”

    First of all, thank you for clarifying that you only think certain microbes are good for frequent ingestion. I apologize for writing so much that attacked the idea that any microbe exposure is good for you (the impression I got reading many of your posts discussing spending time around sick people and dumpster dive for food with microbes on it etc).

    Seth: I have proposed two ideas. 1. Regular intake of food-associated microbes (in large amounts — e.g., fermented foods) is good for us. 2. Exposure to all microbes in small amounts — amounts large enough to stimulate the immune system but small enough so that the immune system gets rid of them quickly — is good for us and we do various things to expose ourselves (early warning system). If you disagree with #2 — apparently you do — I would like to know why.

    Yes, many microbes in fermented foods can be good for us. And this idea came from medical researchers, not you, like back in 1986 http://www.ncbi.nlm.nih.gov/pubmed/2666378

    Seth: That paper barely mentions fermented foods. It says yogurt is good for people with lactose intolerance. My claim — and my evidence — are much broader. Nor does that paper say that humans need regular intake of food-associated microbes, which is the whole point. If some nutritionist or health organization or anybody associated with health care has said we need regular intake of food-associated microbes to be healthy, please provide an example (e.g., a link). Look at any mainstream book about nutrition and you will see that what I am saying is novel.

    What part of your hypothesis, which you have now clarified to be almost exactly in line with medical research, was ignored by the medical establishment again?

    Seth: My ideas #1 and #2. And my claim that tonsillectomies are idiotic. Again, it should be easy to show I’m wrong. Just provide a link.

    “Seth: Radiation hormesis involves intracellular repair systems. The immune system is another sort of repair system.”

    Yes. A COMPLETELY DIFFERENT SORT OF REPAIR SYSTEM. Seriously, are you saying that the INTRAcellular machinery (think little proteins in a single cell that cut and paste DNA) that repairs DNA damage (like strand breaks, indels, base analogues, etc) is the same as an EXTRAcellular immune system made up of T cells, B cells, macrophages, neutrophils, antibodies, complement etc? Please tell me you’re not.

    Seth: “The same as”? Of course not. Two things can have similarities without being “the same as” each other. In this case the similarity between intra-cellular repair systems and the immune system is generalized benefit from stimulation. Stimulation by X provides protection against Y.

    “You have ignored my broad point that the problem of antibiotic resistance can likely be solved by improving immune function. Another simple idea I haven’t heard from insiders.”

    I have not. A quote from me above “There are diseases out there that will still infect you no matter how strong your immune system is (MRSA, B. anthracis, tuberculosis, the list goes on) and that is what we need antibiotics for (and of course antivirals for the major viral diseases)”
    To elaborate: you haven’t heard it from insiders because insiders know that there is no reason to believe an improved immune system will protect you from all disease. People will always get sick, and we will always need antibiotics.

    Seth: Just because “people will always get sick” doesn’t mean antibiotic resistance will always be a problem. Your main claim (“There are diseases out there that will still infect you no matter how strong your immune system is (MRSA, B. anthracis, tuberculosis, the list goes on”) is unsupported by any evidence I can find. Here are examples of articles that argue that a better immune system helps fight off MRSA:

    http://suite101.com/article/new-treatment-for-mrsa-may-include-boosting-the-immune-system-a287293
    http://www.ncbi.nlm.nih.gov/pubmed/22665379
    http://www.ncbi.nlm.nih.gov/pubmed/22164166

    Re tuberculosis: Huh? Surely you’ve heard of TB vaccines? The fact that you, who identify yourself as an insider, appear unaware of TB vaccines supports my point about insiders ignoring the immune system. Including simple obvious stuff about it.

    If the bacteria are resistant to the antibiotics we use, we need new antibiotics. Bacteria have co-evolved with us for millions of years, and with antibiotics more extensively for the last century. They have intricate cellular machinery to attack us that is just as complex and profound as the immune system is. Upping our immune “power” will not protect from all pathogens. We need all the tools in the toolbox to defend ourselves, particularly vaccines and antibiotics.

    quick aside to Andrew: where in the post did Seth mention medical research’s incentive system?
    Jill: see my response to Seth above.

  23. Eugene Woodbury Says:

    The consumption of microbes is enjoying a fast food revival in Japan. Aspergillus oryzae even has its own cute mascot: http://blog.japantimes.co.jp/japan-pulse/moldy-mos-burger-confirms-koji-boom/

  24. Adam Says:

    Another cool non-antibiotic cure for bacterial disease: fecal transplant.

    http://en.wikipedia.org/wiki/Fecal_bacteriotherapy

    “Benefits of FMT include the restoration of the colonic microbiota to its natural state by replacing missing Bacteroidetes and Firmicutes species, eradication of C. difficile, and resolution of clinical symptoms such as diarrhea, cramping and urgency. Antibiotic resistance in CDI is an uncommon event- rather CDI relapses due to the presence of C. difficile spores[19]. Although once considered to be ‘last resort therapy’ by some medical professionals due to its unusual nature and ‘invasiveness’ compared with antibiotics; perceived potential risk of infection transmission; and lack of Medicare coverage for donor stool, the recent position statement by specialists in infectious diseases and other societies[1] is moving away from FMT as a last-resort treatment and toward acceptance of FMT as standard therapy for relapsing CDI and also Medicare coverage in the United States. Indeed the Editor-In-Chief of the Journal of Clinical Gastroenterology, Dr Martin Floch, announced in a recent editorial that “FMT using donor stool has arrived as a successful therapy”[20]. Given that antibiotics are the original cause of CDI through their damage of the normal human flora and removal of protective Bacteroidetes and Firmicutes species, further antibiotic therapy should be avoided. It has now been recommended that endoscopic Fecal Microbiota Transplantation be elevated to first-line treatment for patients with clinical deterioration and severe relapsing C. difficile infection[5]. The earlier the infusion is initiated, the less likely the patient’s condition will deteriorate, thereby preventing the higher mortality rate associated with severely affected patients. Fecal Microbiota Transplantation is being increasingly used in clinical practice and since complications of FMT are so rare its use is likely to increase exponentially in the coming years.”

    Seth: Very interesting, especially the low complication rate.

  25. Chris Says:

    Still the tonsillectomies thing?? Did you not read the Mayo clinic guidelines are posted? Tonsils are no longer removed for flippant reasons like a one-time infection. They are removed for things like cancer of the tonsils, and extremely painful recurrent infections that hamper quality of life.

    Seth: I read the Mayo Clinic guidelines long ago. Unlike you, apparently, I don’t believe everything I read on the Mayo Clinic website. Only a small fraction of tonsillectomies involve cancer of the tonsils. For “recurrent infections”, tonsillectomies are ineffective — see the latest Cochrane Review.

    “Seth: “The same as”? Of course not. Two things can have similarities without being “the same as” each other. In this case the similarity between intra-cellular repair systems and the immune system is generalized benefit from stimulation. Stimulation by X provides protection against Y.”

    Except when it doesn’t. Please provide any evidence that exposure to a nonpathogenic bacterium throughout the lifespan (not just in development, which is discussed in the hygiene hypothesis) increases immune response to a different microbe, via either increased innate or adaptive immunity.

    Seth: See studies of how probiotics reduce colds and other infections. I provided links to them on my umami hypothesis page.

    Also, thanks for doing my research for me. You just cited two studies from Pubmed that cite real medical researchers doing research on..wait for it… the immune system!! What happened to this? “those who run our health care system ignore the immune system”

    Seth: I didn’t say it was completely ignored. Of course not.

    Also, if you actually read the paper,

    Seth: Which paper?

    they do not do what you say they do. No immune system is “improved” through our intervention
    (although I applaud you for finally deciding to search pubmed instead of just claiming you know things). In the PVL paper, the PVL cytotoxin SECRETED BY THE BACTERIA increases the immune response. This was not a treatment that boosted the immune system, it was a finding that this specific type of bacteria is going to be associated with better outcomes because your immune system recognizes it better (this is a simplistic explanation, but captures the idea).

    The staph aureus paper, if you read beyond the “immune enhancement” title, actually involves injecting P4 along with a pathogen specific antibody. This is a form of chemotherapy, it just doesn’t happen to involve antibiotics. It is still a drug however, and it doesn’t just magically “boost” the immune system. You add antibodies that are specific to the bacteria into the blood, they coat the pathogen, your body recognizes them like any other antibody and engulfs the bacterium. It is just another tool to use against tough to treat diseases. No one is throwing out antibiotics because of these tools, because bacteria will become resistant to things like pathogen-specific antibodies via mutations just like they would become resistant to antibiotics. All of theses forms of research are useful and will hopefully give us enough options to treat future disease, but none is perfect on their own.

    Seth: I fail to see how all this supports your claim that “There are diseases out there that will still infect you no matter how strong your immune system is (MRSA, B. anthracis, tuberculosis, the list goes on)” — as if, when it comes to these diseases, strength of immune function didn’t matter.

    “Re tuberculosis: Huh? Surely you’ve heard of TB vaccines? The fact that you, who identify yourself as an insider, appear unaware of TB vaccines supports my point about insiders ignoring the immune system. Including simple obvious stuff about it.”
    And if you had in-depth knowledge about TB vaccines instead of knowledge from Google University, you would know that the TB (aka BCG) vaccine is one of the least effective vaccines we have (approximately a 50% success rate) http://www.ncbi.nlm.nih.gov/pubmed/8309034 and that active research to make a better one is underway. If we had a good vaccine, TB wouldn’t be such a massive worldwide problem http://www.ncbi.nlm.nih.gov/pubmed/22608339 .
    Currently MDR-TB (multi drug resistant TB) is one of the most devastating global pathogens. New antibiotics developed to treat TB (the second line antibiotics) have saved countless lives, but now TB is resistant to those as well, and we are looking for more.

    Seth: I don’t see how any of this makes your claim that TB “will still infect you no matter how strong your immune system is” less wrong. As shown by the (partial) effectiveness of TB vaccines, the immune response to TB matters a lot. Stronger immune system –> less need for anti-TB antibiotics –> less concern with multi-drug resistant TB. I am unable to figure out what part of this reasoning you disagree with, and why.

    “Seth: I have proposed two ideas. 1. Regular intake of food-associated microbes (in large amounts — e.g., fermented foods) is good for us. 2. Exposure to all microbes in small amounts — amounts large enough to stimulate the immune system but small enough so that the immune system gets rid of them quickly — is good for us and we do various things to expose ourselves (early warning system). If you disagree with #2 — apparently you do — I would like to know why.”

    Sigh. Okay, I’m done trying to assume what you are trying to say, because you keep re-clarifying your statements (moving goalposts). Please provide peer-reviewed research, ideally with a plausible mechanism, that explains your points 2 and 3. Also, explain how point 3 is different from the widely researched hygiene hypothesis. For point 2, explain how it is different from probiotics. I didn’t cite that paper as a specific example of a paper that said fermented food was good for you, I cited it as an example that probiotics had been in the literature for 30 years.

    Seth: The notion that yogurt is good for us is more than 100 years old. There is a big literature on probiotics, of course. If you think the idea that yogurt and probiotics are good is the same as my umami hypothesis (yogurt and probiotics do not taste of umami), fine, let’s move on. How my point 2 (early warning system) is different from the hygiene hypothesis: I am saying all of us (not just children) actively do things to expose ourselves in tiny amounts to the microbes around us. We actively self-vaccinate. The hygiene hypothesis says nothing about self-vaccination.

    Finally, please don’t just self-cite your old posts again. I read them, and magazine articles that talk about elephants liking beer don’t count as scientific evidence. Please show me the relevant literature that spells out a plausible mechanism that explains exactly your statement “Regular intake of food-associated microbes (in large amounts — e.g., fermented foods) is good for us.” –Specifically why the intake must be regular, and why the microbes must be food associated. Otherwise you are just talking probiotics and normal flora, which is nothing new. Also explain this “Exposure to all microbes in small amounts — amounts large enough to stimulate the immune system but small enough so that the immune system gets rid of them quickly — is good for us and we do various things to expose ourselves (early warning system).” –specifically how the immune system is stimulated by these microbes, and what changes in the immune system we can expect from this exposure. Give solid evidence why things like touching our mouths means we are sampling bacteria and not just itching. As I side above, clearly explain why this is not just the hygiene hypothesis.

    Seth: I cited two kinds of evidence (both peer-reviewed) for the early warning system idea: 1. people frequently touch themselves near their mouth. (Your “itching” explanation: read about the differences between “proximate” and “evolutionary” explanations. Both may be true.) 2. “group immunity” data with insects. I could have added (peer-reviewed) data about 3. Placement and function of tonsils. 4. Effect of loss of tonsils (very bad long-term). These 4 lines of evidence have never been proposed to support the hygiene hypothesis.

    Enough hiding behind old posts and vague explanations. If you really know your stuff, I want coherent, testable hypotheses that are proven true by scientific experiments.

    Seth: My post put forth an obvious idea: If our immune systems were much stronger, we would need to use antibiotics much less. If we used antibiotics much less, antibiotic resistance would be much less of a problem. Are you still saying this is WRONG?

  26. Vas Says:

    Hi Seth,

    I was referred to your excellent blog by Allen. I know very little about medicine, but I can tell you that when I go to Ukraine I find a different approach. Antiviral medicine is freely available and affordable (from personal experience it works – though that could be a placebo effect). There are also sprays that are said to stimulate the immune system (prescribed by doctors.. may have been a hormone, I could find the name if you were interested).

    Vasiliy

    Seth: By Allen you mean Allen Neuringer? Yes, I am interested in the name of these sprays that are said to stimulate the immune system. I have not heard of them.

  27. Vas Says:

    Yep, Allen Neuringer.

    Interferon is what my sister was prescribed by a doctor for her kids to do something like boost their immune system if they were to be in an environment where they were likely to get sick (e.g., around other sick kids). The wikipedia page seems to suggest that interferons do indeed have something to do with the immune system.

    For less medical things, there are echinacea sprays that are said to boost the immune system (apparently there have been some scientific trials that suggest echinacea decreases the duration of a cold).

    Seth: That’s interesting, thanks. I didn’t know about echinacea sprays.

  28. Patrik Says:

    Removing tonsils because of too many infections makes as much sense as removing part of the brain because of memory loss.

    What? Are you implying that physicians actually treat the cause, and not the symptom? HOW DARE YOU? ;P

  29. Vas Says:

    Of course echinacea sprays/teas are not prescribed by M.D.s, but I’ve had positive experiences with them.

  30. Chris Says:

    Hi Seth,

    Been without internet for a few days, saw you had a new post on this topic, so I will put more emphasis on responding to that, but in brief I will address your closing comment:

    “Seth: My post put forth an obvious idea: If our immune systems were much stronger, we would need to use antibiotics much less. If we used antibiotics much less, antibiotic resistance would be much less of a problem. Are you still saying this is WRONG?”

    Yes. Probably not the part that you think though. If we used antibiotics much less, there would be less antibiotic resistance, yes. However, you have no evidence that if our immune systems were much stronger, we would need to use antibiotics much less. First of all, you still cannot clearly define what a stronger immune system consists of. Secondly, you have not shown data shown that “XYZ” indicator of improved immune function was shown to be protective against “ABC” disease. Finally, you haven’t taken into account the fact that oftentimes, people get sick not because their immune system is deficient, but because the microbe simply has better mechanism of attack than your body has of defense. Even if the body’s current immune mechanisms were improved (whatever that means), if a microbe has bypassed the immune system, it won’t matter (e.g. staph aureus had a protein A on its surface that binds antibodies in reverse, preventing normal immune response, a higher titer of antibodies would not necessarily then lead to a better disease outcome. There are thousands of other examples of similar mechanisms bacteria use to defeat the immune system (phagosome survival, altered membrane charge, etc)
    Just because something seems “obvious” doesn’t mean it is right.

    @ Patrick

    And when you cannot treat the underlying cause, treating the symptoms is better than nothing, no? Painkillers do not treat the underlying cause of migraines, but they can sure help.

    @ Vas

    N=1, placebo effect (that actually describes a lot on this blog)

    Seth: You write “you have no evidence that if our immune systems were much stronger, we would need to use antibiotics much less.” When I started to sleep much better, I got colds much less than previously and much less than most Americans. This suggests that most Americans would get sick less if their immune function was improved. The most interesting part of your answer is “oftentimes, people get sick not because their immune system is deficient, but because the microbe simply has better mechanism of attack than your body has of defense.” This view implies that “oftentimes” variations in immune function have no effect on probability of getting sick. What is your evidence that it has EVER happened that strength of immune function made no difference? I believe there is none.

  31. Vas Says:

    Chris, I make no claims about the efficacy of echinacea (in terms of improving immune function), and perhaps it has been a placebo effect in my case, but I can say that N is substantially greater than 1.

    Here are just some of the studies:

    http://www.umm.edu/altmed/articles/echinacea-000239.htm