Monday, September 15, 2014

Antibiotic Pioneers

In 1928, Scottish scientist Alexander Fleming was fiddling around with a strange mold he found growing on a Petri dish. This mold was known as Penicillium notatum and after an accidental exposure of the Penicillium to a Petri dish containing Staphylococcus (an infectious microbe), Fleming discovered that the exposure resulted in destruction of the Staphylococcus. This was an amazing discovery and he soon learned he now had the power of life and death over a wide range of Gram-positive bacteria that had been stymieing doctors for centuries!  Fleming toyed with the moldy medicine for well over a decade with little success in making a commercially viable, purified form of his invention: penicillin.


At about the same time, across the pond, U.S. scientist Selman Waksman was also tinkering with microbes and developing a long list of antibiotic compounds with targeted therapeutic value.  By the 1940’s his lab had developed streptomycin, chloramphenicol, and tetracycline, all produced by soil bacteria. Selman Waksman was a student of dirt. In 1927, he penned his treatise Principles of Soil Microbiology and continued to devote his life to studying the invisible life living in the mud of the Earth.  Soon, Dr. Waksman learned to harness this invisible life and by 1942, he was producing large quantities of these antibiotic molecules that would selectively lay waste to a large range of microbes. These antibiotics were far more powerful than Fleming’s penicillin, killing both Gram-negative and Gram-positive microbes...we now had complete control of the invisible life within us. His focus was on agriculture and keeping our crops healthy and profitable, but the 1940’s had bigger plans for Waksman’s efforts.

  
Dr. Waksman died in 1973, but the true depth of his contribution to modern society is just recently coming to light. The microbes may have indeed made this a better world to live in, but not for us—for them.  For, you see, what Dr. Waksman did not predict, or chose to ignore, microbes have a few tricks up their sleeve.  At the natural, tiny, ‘signalling molecule’ level, microbes play by the rules they developed over billions of years, but when continually slathered and bathed in the toxic substance, microbes won’t stand by and be wiped out—they adapt and overcome.

  
The bacteria of the world secrete over 2200 different antimicrobial peptides, known as AMPs, that have been so far cataloged.[11] [12] [13]  In addition, our own immune cells known as Paneth cells secrete antimicrobial chemicals such as defensins and AMPs. The natural antibiotics and antifungals secreted by our silent commensals and our guts cells tend to be selective and targeted toward pathogenic species and not harmful toward themselves or non-infected tissues.[14] Clinical doses of pharmaceutical antibiotics in relative comparison elicit carnage to a magnitude and scale akin to weapons of mass destruction. Both friends and foes are destroyed but what typically remains standing are the hearty pathogens which then take the initiative in the absence of our allies. Humans and animals all harbor ‘pathogenic’ strains of microbes like C. difficile, Staphylococcus, and haemolytic E. coli, yet neither infection nor disease may ever occur because the gut is guarded by plenty of beneficial commensals like Lactobacilli, Bifidobacteria, good E. coli, and other major microbial species.

Special thanks to Dr. Grace Liu, PHARMD, from Animal Pharm for contributions to this article.

[11] Nakatsuji, Teruaki, and Richard L Gallo. "Antimicrobial peptides: old molecules with new ideas." Journal of Investigative Dermatology 132 (2012): 887-895.
[12] Wang, Guangshun, Xia Li, and Zhe Wang. "APD2: the updated antimicrobial peptide database and its application in peptide design." Nucleic acids research 37.suppl 1 (2009): D933-D937.
[13] Silva, PM. "Defensins: antifungal lessons from eukaryotes." 2014. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3960590/>
[14] Yeaman, Michael R, and Nannette Y Yount. "Mechanisms of antimicrobial peptide action and resistance." Pharmacological reviews 55.1 (2003): 27-55.

43 comments:

  1. It's good to know that the good guys I've built up in my body by eating homemade fermented foods and lots of prebiotics (especially resistant starch) are helping keep the bad guys at bay.

    I'm prone to yeast infections in skin creases in hot weather but these have almost disappeared since I started the above-mentioned regimen. I did let things slide recently and the yeast infections came back again, which was excellent motivation to get back to eating potatoes, green bananas and ferments. :-)

    ReplyDelete
  2. Two questions, a bit off-topic.
    What're your thoughts on cocoa powder? I buy mine at Whole Foods because they sell a kind that is 'non-alkalized', which I guess means that it hasn't been heat-treated, as opposed to 'dutching'. They also have this kind of cocoa powder at Starbucks that you can add to coffee. I always add a generous shake. Is this shit good or bad for me?

    2. Do you use honey? I know that not all honey is created equal, but the fructose is so high. Wheatbelly advocates stevia and xylitol and not honey. But I like honey. What say you, tatertot?

    ReplyDelete
    Replies
    1. I like cocoa powder in moderation, It's high in theobromine, a purine, which is a good antioxidant but you can over-do it. A 'generous shake' is fine, an ounce or two of 100% chocolate is fine, but eating a whole bag of cocoa nibs or a whole bar of 80-100% dark chocolate every day is too much, but who would do that?

      I love bee products in general, especially if they are from locally raised bees. I'm not a big fan of Safeway honey. Find some local beekeepers at a farmers market, get local honey and use sparingly.

      Also see if they have pollen granules you can buy, I think these are worth their weight in gold!

      Just yesterday I bought a jar of local honey that has a big chunk of beeswax in it. It was a pint-sized jar, it will last me probably til Christmas. I usually just eat honey off a spoon or sometimes in tea. I never use it in large quantities. I use stevia in my daily coffee.

      Delete
    2. " Find some local beekeepers at a farmers market, get local honey and use sparingly."

      I do not agree with "sparingly". Why? NATURAL FRESH honey is so powerful in healing. Those looking at its sugar content only are blind.

      See:
      Lactic acid bacterial symbionts in honeybees – an unknown key to honey's antimicrobial and therapeutic activities
      http://onlinelibrary.wiley.com/enhanced/doi/10.1111/iwj.12345/

      "Could honeybees' most valuable contribution to mankind besides pollination services be alternative tools against infections? Today, due to the emerging antibiotic-resistant pathogens, we are facing a new era of searching for alternative tools against infections. Natural products such as honey have been applied against human's infections for millennia without sufficient scientific evidence. A unique lactic acid bacterial (LAB) microbiota was discovered by us, which is in symbiosis with honeybees and present in large amounts in fresh honey across the world. This work investigates if the LAB symbionts are the source to the unknown factors contributing to honey's properties. Hence, we tested the LAB against severe wound pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa and vancomycin-resistant Enterococcus (VRE) among others. We demonstrate a strong antimicrobial activity from each symbiont and a synergistic effect, which counteracted all the tested pathogens. The mechanisms of action are partly shown by elucidating the production of active compounds such as proteins, fatty acids, anaesthetics, organic acids, volatiles and hydrogen peroxide. We show that the symbionts produce a myriad of active compounds that remain in variable amounts in mature honey. Further studies are now required to investigate if these symbionts have a potential in clinical applications as alternative tools against topical human and animal infections."

      Delete
    3. And one more on honey, though I could spam it here with honey papers.

      Can you see why the mass produced monofloral honey is not the best choice?

      Kynurenic acid in honey from arboreal plants: MS and NMR evidence
      http://www.ncbi.nlm.nih.gov/pubmed/17999354

      (TRP = trypthophan, KYNA = kynurenic acid)

      "KYNA, a Trp metabolite, shows neuroprotective activity against excitotoxic amino acids by antagonizing the NMDA receptor (glycine, glutamate). Here we report the identification of KYNA by a combination of ESI-MS/MS and 1D- and 2D-NMR analyses in honey varieties of arboreal origin. KYNA are absent in single-flower honeys from herbal flowers. These different distribution patterns might possibly involve an indirect plant defence mechanism against fungal pathogens and herbivorous parasites, ever-present on wild trees. The presence of KYNA in honey may explain its pain-relieving effects reported in the literature. The substance, acting in concert with honey flavonoids (COX-2 inhibitors), by antagonizing the NMDA receptor may contribute to the antinociceptive effect of honey. Moreover, kynureninates, owing to their antimicrobial properties, can favour the successful outcome of wounds and burns."

      Delete
    4. Gemma,

      Dont forget about Manuka ---which can be bought at stores :) I used this in the beginging to heal as well http://www.webmd.com/a-to-z-guides/manuka-honey-medicinal-uses http://en.wikipedia.org/wiki/M%C4%81nuka_honey many countries but GOOD OL USA use it for wound healing :)

      Delete
    5. and other good link on propolis or pollen ---hadza eat ----these

      http://www.hchs.edu/literature/Bee_%20Pollen-Propolis-and-Royal_Jelly.pdf

      Delete
    6. Gemma - Thanks. Honey is amazing. I guess by 'sparingly' I was thinking about the price and not using it as a sugar substitute. Some people, like me, tend to get carried away with these tasty healthy foods and end up eating way to much of a good thing. Around where I live, local honey costs about $20 a jar vs $5 for supermarket honey.

      My wife asked, 'Why don't you just buy some beehives?' after I spent 80 bucks at the farmer's market on bee products. Who am I to disappoint? I think I'll get some bees next spring!

      Delete
    7. Have you ever tried fermented honey? Wondered what it tasted like before I bought a jar.

      Delete
    8. I've had mead. Is that what you are referring to? Are there other fermented honey's?

      Delete
    9. It does say it is the main ingredient in Mead which I have never had.

      Delete
    10. Well Tim, at least where you live you don't need to concern yourself about neo-nicotinoids, however it's spelled. Given the length of the winter, wouldn't you have to make sure your bees are well fed during that time? I find it appalling how commercial beekeepers feed their bees sugar water during the winter. Bahhh!

      Delete
    11. Kinda sad, but honey bees won't 'overwinter' here. They all die. Treated as an 'annual'. It's the biggest reason I have resisted. I heard there is a facility nearby that will overwinter bees in a somewhat heated building, but I've heard they have big die-offs in the past. 8 months of Winter just too much for the poor guys.

      I'm looking into it, though. I see lots of hives around and several beekeepers at every farmer's market.

      But, no, no problem with GMO crops, pesticides, or any of that.

      Delete
    12. there's nutritionist on the radio selling honey or propolis or pollen from bees he says are in up in Canada and i think he claims they survive -55 degrees or something.

      Delete
    13. Oh that's horrible. :-(
      You need a little shed for them with a heater!

      Delete
  3. Great article

    And LIKE I say.....your using a MOLD/yeast to destroy things....it then can run wild...why you see many with elevated liver enzymes with amoxicillin... Which I know this drug gave me crohns -- due to my high gene make up of HLA DQ anyone who suspects you have yeast problems Dont take this drug..... as the article says... HIGH LACTO and BIFIDO strains help protect you..... 2 years of lowering yeast and massive BIFIDO and LACTO ---- problem solved .

    ReplyDelete
    Replies
    1. I was just reading something that said almost everyone who is immune compromised gets skin yeast overgrowths. As common as jock itch, athletes foot, and eczema is, that should tell you that there are lots of immune compromised people.

      When I was really bad, I'd get great big itchy patches of dry, red bumpy skin on my forearms and calves. Doc would just say 'hmmmmm?' and give me steroid cream.

      Delete
    2. yes...tim My whole point,,

      the steroid cream reduces inflammtion but FEEDS yeast... so the problem comes back later. Im reading alot on yeast, lacto and bifido ..as well oxalate bacterias--- its as almost they work hand and hand. It may be the oxalate bacteria break down oxalate ---so do lacto or bifido. Im starting to think these--- work hand in hand-- lacto, bifido or oxalate with yeast. you see autism kids have problems with oxalate foods -- and they also have problems with gluten and grains... So my mind spinning there high in yeast--- and missing oxalte / lacto / bifido degrading bacterias. . so its a no wonder there a mess with grains starch, milk

      many immune compromised people have antibodies high to ASCA or AMCA yet no one -- looks here ... to me the yeast are out of control from like we say missing bacteria. when my gut failed ,,,, I had a rash on my belt pants line...... I always got athletes food off and on all my life....as well back and forth hemorrhoids --- gone When you look at you doc office its get in GET you out for symptom -- everything is steriods or anti inflammtory ??? same with sinus ear nose and throat. sinus spray is a steroid. when all this happen I said shit... im sure - since my sinus is a mess...since I hack crap out every morning im re infecting my self at night with nasal drip------ why I also attached my sinus... olive leaf extract spray and grapefruit extract spray and coconut oil... today I have the best sinus in my life.... I dont use anything for it now....no seasonal allergies as well...

      Delete
  4. Thank you for those articles, Gemma. I am the not-so-proud owner of a really messed up microbiome, which is why I'm here. Things that are supposed to help tend to make matters worse, but I'm not giving up. If I understand the abstracts correctly, honey has some probiotic properties. It sounds like it would be worthwhile to try. Luckily, I live in an area where local raw honey will be easy to find.

    ReplyDelete
    Replies
    1. Heck, yeah! Give local honey a try. Find a beekeeper and get it right from them. They will know ALL about honey and will talk your ear off. Bring plenty of money, lol.

      See if they have the pollen granules, they usually keep it in a refrigerator.

      And propolis.

      Read all you can about these things!

      Have you gotten any gut tests? Do a uBiome and let me post your results. $89 is all it costs. It will miss things like yeast and parasites, but it will give you a clue to the diversity of your microbiota.

      Delete
    2. KathyKpsd,

      Do you live in the USA???? use labcorp?? can you get your doc to do this IBD EXPANDED PANEL labcorp test Test Number: 162045 CPT Code: 83516(x3); 86255; 86671 Inflammatory Bowel Disease (IBD) Expanded Profile

      I had hemorrhoids all my life... off and on... 5 surgeries to cut them out from 17 years to 38--- today im 41 ZERO hemorrhoids in 2.5 years

      the test above test the following antibodies-- ALCA ACCA ASCA and AMCA... ASCA is bakers brewers yeast in my case my level was normal

      doctors usually use the IBD panel only which tests ASCA
      Atypical perinuclear antineutrophil cytoplasmic antibodies (pANCA); Saccharomyces cerevisiae, IgA;
      Saccharomyces cerevisiae, IgG
      related to -- bakers brewers yeast

      You maybe in a situation where your yeast ---- maybe related to AMCA like my self. once I got rid of the antibodies to this NO more hemmriods for me

      If you look at hemorrhoid creams are a suppository like preparation h --they equal steroids ... which reduce that inflammation but feed yeast-- SO they come back

      Delete
    3. Hi Eddie,

      Is the Promethius IBD sgi diagnostic a substitute for Labcorp's IBD Expanded panel?

      http://www.prometheuslabs.com/Resources/IBDDiagnostic/IBDsgi-ProductDetailDX13005-0113.pdf

      Thanks.

      Delete
  5. Great minds, Tim! I have my uBiome kit waiting at home. I was on vacation and not eating my typical diet (and paying for it now, big time), so I emailed them to see if I need to wait until things get back to their usual state before doing the test. Can't call it "normal." Do you have any thoughts on that?

    ReplyDelete
    Replies
    1. I think 6 weeks seems to be the sweet spot for microbiome to adjust to a new routine, but it actually changes meal-by-meal.

      I'd eat just like you know you should for 6 weeks and then do the test.

      Delete
    2. I appreciate your help so much! I wish I could eat the food I know I should. TMI alert: my current state of affairs is bleeding hemorrhoids so severe that I sometimes need to change clothes. I've had this off and on, but I fear fermented food and resistant starch (just the amount in cooked/cooled potatoes) is making matters worse. :( Should be an interesting result from uBiome. I saw a GI doc (one of a long string) who apparently did not feel this was cause for concern. He did an SIBO test that came back negative, suggested the FODMAP diet, which I already told him didn't help, though those are among the foods I react to, and failed to investigate further. I am trying to get a referral to an integrative health clinic.

      Delete
  6. Hey Tim, do you usually peel your spuds before cooking? I'm guessing you keep the skin on when making baked potatoes, but I tried steaming potatoes tonight. I peeled them, then sliced them into very thin slices using a mandolin. I actually cooked 4 potatoes in half an hour this way.

    ReplyDelete
    Replies
    1. one more thing,
      according to the chart on FTA and RS
      potatoes – Roasted and Cooled 19.2
      Potatoes – Steamed and Cooled 5.8

      So I guess I should only roast potatoes? That's a radical difference between roasting and steaming. After steaming all those potatoes and cooling them overnight, they still are pretty low in RS. Or not?

      Delete
    2. I rarely peel home grown potatoes, nearly always peel store bought potatoes. If I'm served a baked potato with skin in a restaurant, I'll eat the skin.

      On those FTA RS charts I made, don't bank on the numbers! They were gleaned from dozens of papers, some old, some new...just whatever I could find. Bottom line though:

      To maximize RS3, cook, cool, and eat cold or reheat. Beans and potatoes are the best 'normal' foods for RS. Cooked and cooled plantains, taro, corn, and rice also will for RS3...amounts vary wildly depending on variety.

      There are no good RS3 lists, and probably never will be. It is time, temp, and species specific..and hard to measure. Just pre-cook and serve most of your starches as leftovers and you are good to go. It's not worth wasting many brain cells over.

      Delete
    3. Also as Tim filled me in, to do the AOAC measurements for RS3, they have to FLASH FREEZE THE SAMPLE which automatically will enrich RS, no???! wtf everything is actually over-rated but like glycemic index, the food is less 'digestible to human hosts' but not the microbes when there is a matrix of stuff
      --fats
      --fiber, NSP
      --slow digesting starch (SDS)
      --PROTEIN
      --RS3 gelatinization and crystallization
      --etc factors (less salt, microbes, acid, microbial acids, cooling times/temps, etc)

      Delete
    4. Well, hello, Grace! Nice to see you around these parts. I quit trying to measure the RS and just eat my starches as leftovers. Makes too much sense and too easy.

      I think AOAC method is fine for raw starches, but not cooked. The old ileostomy studies did good measurements on RS3, though. Those I believe, there's just not a huge database of foods compiled for those.

      Delete
    5. Wonderful blog Tim~! Do you think all ileostomy patients have healthy small intestines? Yes those are great studies!

      Delete
    6. That's the 'big unknown' isn't it?

      I should do a post on it soon, but the progression in RS content measurements went from ileostomy studies to dog studies to chemical studies. In all cases, they used the ileostomy results as the 'gold standard' to measure against.

      The dog studies were pretty brutal, they outfitted dogs with multiple collection tubes and gave them human digestive enzymes. Later, they used humans to pre-chew the foods and then dissolved the chewed up food in digestive enzymes.

      The method they use now works well for RS2, but probably not RS3.

      Delete
    7. Maybe our own gastric acidity makes RS3 more resistant to microbial fermentation, even with bile acid effects in the small intestines? The food matrix and chyme composition may ultimately also effect the total RS3 recovered and most ileostomy studies are isolated food, not 'meals' per se. Very complex, but not really. I think what our ancestors did is what our gut favors! Very nice blog Tim!!

      Delete
    8. Yep! The full fiber spectrum. Get your RS3 from leftovers, RS2 from raw, and all the others from a variety of fruits and veggies, cooked or raw.

      The worst thing would be to exclude starches and/or fiberous foods.

      Exact numbers are impossible to say, but the 20-40g range we came up with reading all those papers still seems about right, don't you think?

      But you don't really need to count...just eat your starches as leftovers, and a wide variety of plants daily. Good to go.



      Delete
    9. Yes good to go!! I bet every place on earth has their own local spectrum of regional starches+fiberous foods, along with it attached all the microbes that have the tools and cutters to break them down. Japanese guts have algae-enzymes that are only found from microbes on Japanese algae. I think the Burkino Faso kids are able to consume much wider range of cellulose and insoluble fiber based foods because their diverse guts have termite intestinal microbes in them from eating termites!

      Delete
  7. Reading:
    Obama Plan to Fight Antibiotic Resistance ‘Disappointing,’ Critics Say
    http://time.com/3399231/obama-antibiotic-resistance/

    Any comments?

    ReplyDelete
    Replies
    1. The real tragedy is found between the lines:

      "Already, Perdue, one of the country’s largest producers of poultry, announced that it will no longer use human antibiotics with 95% of its chickens."

      and

      "...the FDA allowed 18 antibiotics that it rated as high risk to human health to remain on the market, where farmers used them to boost the feed and water of their animals."

      Boost the feed and water? What the heck does that mean?

      Oh, I see:

      "And most of the animals receiving antibiotics aren’t sick, but are fed low doses of the drugs in order to grow faster and larger."

      So, taking antibiotics makes the animals fatter! They can be slaughtered earlier, they don't need to live long lives, just get fat as fast as possible. That surely couldn't have any meaning for humans taking antibiotics now could it?

      Delete
  8. Fermented honey is not mead. Mead is a honey plus water plus yeast mixture that is kept warm (and commercial brands are heated) and allowed to ferment for months into an alcoholic beverage. By US law, fermented honey that is sold to others as honey cannot contain significant alcohol (probably no more than 1% at most), and a license is required to make or sell alcoholic beverages.

    If you try both fermented honey and mead, you'll see that they are quite different. Fermented honey is a honey, whereas mead is more like wine, though different from that as well. I love the taste of fermented honey. Fermented raw honey is the best tasting honey I have ever tried, and I've tried dozens from around the world. However, it all depends on both individual taste preferences and what one is used to, and perhaps one's gut microbiome. My sister tried the same honey and found it to taste bitter, which was quite a surprise to me, because it doesn't taste bitter at all to me.

    Fermented raw honey is also the only type that has given me any noticeable health benefits, albeit seemingly minor (less scalp, eyebrow and forehead dandruff flakes and hair that feels less greasy and softer and needs less cleaning, more like it was in my early youth).

    Fermented honey also has a long and distinguished history for humans and pre-human ancestors going back millions of years back to the first primate and beyond. Some day Paleoists will get around to recognizing this as another "superfood".

    An archetypal food for humans is the naturally-occurring fermented honey and sometimes lightly alcoholic mead in the crooks of baobab trees, when rainwater floods a honey hive in the crook of baobab tree during the wet season. When our ancestors discovered this, it was likely cause for celebration, not for wagging their fingers and saying "Beware: avoid this evil sugar and alcohol. They are pure poisons."

    ReplyDelete
    Replies
    1. Wow! Thanks, dude. I always wondered about that. It never made sense that honey could ferment being all antimicrobial, antifungal and all.

      Delete
    2. Ok can we please please please have a post or more info on how to do this.
      I have a big tub of raw honey in my cupboard...
      Off to google... but something here would be nice... not trying to take over or anything!

      Delete
  9. Paleophil -- I luv ur comments. U ROCK!! also honey fermented in JUN kombucha is special too. Most honey and regular scobies for kombucha would not survive well because honey has natural anti-microbials/antivirals/antifungals... The bugs have to be adapted to the defense protocols and AMPs in honey.

    ReplyDelete
    Replies
    1. everything I read --- is the great effects of RAW honey but used when pulled from the hive --- like going out to dinner (A one meal) When you remove it and store it... yeasts usually take charge and some spore forming bacteria can get in. ( the one man reason honey is so bad for kids)

      Ive read some stuff on depending on how wet or damp it is if a farmer bottles his honey -- can effect it. ( I guess the one reason the HADZA have great success...they eat and use it when they want it for a meal)

      We can see how crappy store pasteurized honey is -- a pill of crap/ sugar. Raw antifungal / anti bacterial... but depending how stored or picked -- you have some introduced issues...

      Delete