Anti-Inflammatory Diet

All health care starts with diet. My recommendations for a healthy diet are here:
Anti-Inflammatory Diet and Lifestyle.
There are over 190 articles on diet, inflammation and disease on this blog
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Wednesday, June 25, 2014

Antibiotic Resistance, Superbugs and Drugs

Antibiotic resistance results, because spontaneous mutations occur so frequently that all bacteria are different.  It is just a matter of exposing enough bacteria to an antibiotic to find one that is insensitive to a particular antibiotic.  More bacteria mean a greater chance of mutations to antibiotic resistance.  The gut contains a lot of bacteria and sewage treatment plants are loaded with gut flora.

Antibiotics are Ubiquitous
All organisms, plants, fungi and animals/humans produce chemicals that kill bacteria, i.e. antibiotics.  I have written many articles about the natural antibiotics of plants, a.k.a. phytoalexins or “antioxidant” polyphenolics, and the human defensins that are peptides with heparin binding domains.  Bacteria also produce viruses, called bacteriophages, that kill other bacteria.  All of these natural antibiotics are small molecules that interact with many different human proteins, and it is these side effects that permit their exploitation as pharmaceuticals.  Thus, statins were selected from fungal antibiotics that inhibited an enzyme needed for human synthesis of cholesterol, metformin was a phytoalexin found to reduce blood sugar and resveratrol is a grape phytoalexin.

Plant Antibiotics are Natural
The flavoring chemicals in herbs and spices have a far more important use in food preparation than titillation of taste buds, since those chemicals kill common food pathogens.  More profoundly, it is important to realize that the selective advantage of phytochemicals/polyphenols/alkaloids/essential oils to the plants that make them, is as natural antibiotics.  Plants kill bacteria, as well as fungi and insects, for a living.

Plant Chemicals Attack all Aspects of Bacteria
Most of the thousand genes that are present in a bacterium code for proteins/enzymes and most antibiotics target those enzymes.  Penicillin binds to an enzyme needed to make bacterial cell walls, streptomycin target protein synthesis, rifampicin blocks RNA synthesis, actinomycin D inhibits DNA synthesis, etc.

Mutation to Antibiotic Resistance is Automatic in Bacteria
Each time a cell replicates, mistakes are made and the new DNA molecule of each chromosome is slightly different than the original.  There are about a thousand genes on the single chromosome of a bacterium and about the same number on each of the 23 human chromosomes.  About a dozen mistakes, mutations, are made each time bacteria replicate.  The mutations that alter the gene target of an antibiotic and produce a bacterial enzyme that is unaffected by the antibiotic, yield an antibiotic resistant bacterium.  The mutant gene now codes for antibiotic resistance and the presence of several resistance genes in the same bacterium produces multiple antibiotic resistant "superbugs."

Mutations are Random, but Antibiotics Select for Resistance
Each cellular replication produces random mutations throughout the bacterial DNA, but of the billion sites along the DNA that can mutate, only a few will produce a modified enzyme that will no longer interact with a particular antibiotic and thus be resistant.  Antibiotic resistance mutants are rare, less than one in a million, but a million bacteria can grow from a single cell in a day and occupy a volume less than a crystal of salt.  Ten hours later, after ten more doublings of the million bacteria, there will be a billion, and there will be a good chance that among those will be a mutant that is resistant to a particular antibiotic.  In the pound of bacteria in the human gut, there are mutants that are resistant to most antibiotics, including the antibiotics that have not yet been developed.  Of course, most of those antibiotic resistant bacteria are just flushed down the toilet.  Treatment with antibiotics kills all of the sensitive bacteria and leaves only the resistant.  Thus, antibiotic treatments select for antibiotic resistant bacteria.

Common Use of Antibiotics Selects for Resistance on Plasmids
Genes are transferred between bacteria by bacteriophages, conjugation (a kind of bacterial sex) and transformation, which is the release of DNA from one bacterium with subsequent uptake by another.  Biofilms, which are communities of many different species of bacteria, stimulate transformation and exploit bacterial DNA as a matrix material to hold the communities together.  The human gut is lined with biofilms and the biofilm bacteria secrete vitamins as the quorum sensing signals that coordinate community activity.  Thus, some vitamins must stimulate transformation, the exchange of DNA among members of the different species of bacteria in the biofilms with evolution of new and novel species.  Rapid change in the gut environment selects for a shift in genes that provide for adaptation to the new environment to small DNA fragments, plasmids, that move most readily between bacteria.  Antibiotic treatment results in antibiotic resistance genes on plasmids.

Use of Multiple Antibiotics Selects for Multiple Antibiotic Resistance Plasmids
Persistent use of an antibiotic will spread resistance to a particular antibiotic through the gut flora, facilitated by antibiotic resistant plasmids.  Replacement of a second antibiotic will result in a new plasmid with both antibiotic resistance genes.  Hospitalization and exposure to a plethora of bacteria with multiple antibiotic resistance plasmids will result in rapid conversion of gut flora to multiple antibiotic resistance upon exposure to any antibiotics.  Hospital staff would be expected to be natural repositories for multiple resistance genes, especially if they are exposed to any antibiotic (or pharmaceutical.)

Most Pharmaceuticals Select for Multiple Antibiotic Resistance Plasmids and Superbugs

The frightening rise of superbugs resistant to all known antibiotics has been attributed to the accelerated use of antibiotics in medicine and agriculture.  Mixing megatons of bacteria in the guts of billions of people with tons of antibiotics, and still more in sewage treatment plants and agriculture, is bound to produce bacteria with every type of multiple antibiotic resistance plasmid imaginable.  But that is not the biggest problem, since fingering the commercial use and misuse of antibiotics ignores biggest exposure of bacteria to antibiotics.  It ignores the fact that most popular pharmaceuticals, NSAIDs, statins, anti-depressants, anti-diabetics, etc., also have substantial antibiotic activity.  Most of these pharmaceuticals started out as phytoalexins and then were found to also have pharmaceutical activity.  Pharmaceuticals are just repurposed natural antibiotics.  When you take an aspirin or Metformin or a statin, you are taking an antibiotic.  When you take a pharmaceutical, you are selecting for multiple antibiotic resistance plasmids in your gut flora and you may be making the next superbug.


Anonymous said...

Chris Kresser states that chlorine
absorbed from pools, showers, and drinking water can also have a negative effect on gut flora. Do you think its something to be worried about?

"While there hasn’t been substantial research on the topic, it’s reasonable to assume that chlorinated water adversely affects beneficial intestinal flora. Chlorine is a powerful antimicrobial agent, and is an effective pesticide against many different strains of bacteria. (10) The compounds in disinfected water may be able to reach the gut not only through our drinking water, but also through daily showers and baths."

Newbie said...

So we are continually killing our own gut bacteria whenever we add herbs and spices to our foods? Something does not feel right about that concept. Am I misunderstanding something in your post?

Dr. Art Ayers said...

Chlorine is of minimal consequence in drinking water, because it interacts with so many other organic molecules in our gut before it has access to living tissue.

I worry about eating processed foods with trans fats, omega-6 oils, HFCS, agave nectar,and grains. Those are major problems that I estimate cause a third of our health problems. Damage to our gut flora by antibiotics, drugs, antibacterial soaps, etc. causes another third. Genetics, environmental toxins, etc. contribute the final third or less.

I doubt that the negative impact of chlorine is noticeable and I don't worry about it. It makes more sense to just eat whole foods, tend to the health of your gut flora and exercise. The rest isn't worth much thought.

Thanks for your comments and questions.

Colleen said...

Dr. Ayers:

Thank you for that clear and concise explanation. Do multiple antibiotic resistant bacteria cause harm to a person by some mechanism while simply residing in the gut or some internal mechanism? Or is the greater concern that a person has some external exposure to such bacteria thereby causing an infection? Thanks again for your informative posts.

Dr. Art Ayers said...

The natural antibiotics, phytoalexins, abundant in plants are effective against bacteria that try to grow in the plant tissue and have a modest effect on bacteria present in food, but by the time they reach the gut flora, they are diluted and have only a slight effect. Similarly, milk is full of enzymes, fatty acids and oligosaccharides that make a toxic environment for adult gut flora, but nourish the specialized gut flora of babies. The gut flora adapts to diet, including the phytoalexins common at each meal.

Eating large amounts of herbs and spices, or any given vegetable and changing frequently, may however, damage gut flora. That is what happens with some extreme fad diets and results in a loss of gut flora diversity and dysbiosis. Plants are difficult for gut flora to digest and special bacteria are frequently required. Absence of adaptation and missing bacteria needed for digestion of particular vegetables is the basis for food intolerances.

Thank you for your questions.

Dr. Art Ayers said...

Multiple antibiotic resistance plasmids are of no consequence themselves and are an extra burden for bacteria to maintain. So your gut flora would be cleared of the plasmids unless continuously exposed to a selective chemical, such as a common drug.

The plasmids are only a problem if you pick up a pathogen and need to treat it with an antibiotic. The pathogen would quickly pick up the plasmid from your gut flora and be resistant to antibiotic treatment. Then it would be called a superbug, even though you made it in your gut.

Thanks for your questions.

Puddleg said...

Hi Art, have you seen this?

TB as a symbiont that supplies NAD precursors when we don't get enough meat.

Unknown said...

This is a very interesting article. Are you saying that essential oils are not healthy to consume then?

Dr. Art Ayers said...

Essential oils are just extracts of the polyphenolics compounds produced by plants to kill bacteria and fungi. These phytochemicals are called antioxidants simply because they have functional groups that react with superoxide and other reactive oxygen species, but their function in plants is as natural antibiotics -- they interact with the enzymes and receptors of organisms. In many cases they are toxic and we have bitter taste sensors to warn us of their presence. Our detox enzymes in the lining of the gut and liver prevent common plants/vegetables from killing us and pregnant women avoid danger to their babies through morning sickness.

Our bodies expend a lot of energy providing protection against essential oils, which are also toxic to our gut flora. I avoid internalization of essential oils and use them externally to reduce inflammation, because some of the compounds stimulate endorphins.

Many drugs are repurposed phytoalexins, so I would expect that some essential oils, which are mixtures of phytoalexins, might act similarly to drugs as selective antibiotics on gut flora with therapeutic effects. I would not use them casually or without the same care as pharmaceuticals, because they are equally toxic. Natural does not mean safe. Nicotine and heroine are in the essential oils of tobacco and poppies.

Thank you for your question.

Kathleen said...

Hi Dr. Ayers,
Do you know anything about proteolytic enzymes (many of which are plant based) and how they may help or harm the body? They are marketed as a near panacea for inflammatory conditions and sports injuries...

Dr. Art Ayers said...

I can't think of any unusual conditions in which protein digestion is a problem that could be remedied by proteolytic enzymes that you eat. I think the point is that proteases are known in plants and people know that proteases digest protein, so there must be some value. But proteins are the easiest food component to digest. It would make more sense to sell enzymes to degrade polysaccharides that humans can't digest. Since the inability to digest plant polysaccharides is the basis for most food intolerances, that would make more sense.

Vegetables are inherently hard to digest (we need bacteria to digest fiber) and are full of polyphenols, a.k.a antioxidants, that are toxic to gut flora, so it would make sense to find ways of making them healthier.

Thanks for your question.

Kathleen said...

Hi again Dr. Ayers,
My understanding is that proteolytic enzymes should be taken on an empty stomach so they can pass through the intestinal wall, enter the bloodstream, and help clear the blood of foreign proteins and other things that cause inflammation.
I am not sure if this is true or even possible. But, from what I have read, they have been used in Europe (Germany in particular) for many years.
Thank you for your response :)

Dr. Art Ayers said...

You can be certain that the plant proteases never leave the gut. Proteases in particular would be highly inflammatory and they would not target foreign proteins, which could also not reach the blood stream without a special transport system. Proteins are too large and are not freely moved in and out of the blood vessels or across intestinal epithelial cells.

If the proteases have any impact, I would expect it to be in the production of unusual peptides or amino acids that might impact gut flora.

Kathleen said...

Much thanks!

dr j said...

here is an interesting PR briefing on an emerging awareness about biofilms in arteries

thank you for your work

Zad said...

Hi Dr. Ayers,
Since you said that essential oils are just as harmful as normal antibiotics how can we treat conditions like Small Intestinal Bacterial Overgrowth. Is a bowel irrigation enough?

Anonymous said...

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My e-mail is

Unknown said...

Hi Dr. Ayers! My name is Cameron Von St. James and I had a quick question for you & was wondering if you could please email me when you have a free moment. Thanks! I really hope to hear from you soon and appreciate you taking the time. ☺ cvonstjames AT gmail DOT com

A.T. said...

Dr. Ayers,

I've been following your blog for some time now. With so much information and misinformation out there, I appreciate having a sensible, scientific (FREE even!) source of information. So, thank you.

Aside from the diet/gut bacteria restoration guidelines you've published here, would you make any special recommendations for somebody who is on long term antibiotic therapy? I'm particularly curious if there is something I should do while I'm actually taking the abx.

I have Lyme Disease and am on my 7th month of antibiotics over the course of two years, with the longest consecutive course of abx being two months and the longest span between abx being about 9 months. I've been on Doxy, Ceftin and now Amoxicillin. I wish I did not have to do this to my body. At this point, I think I am the poster child of how NOT to take care of your gut and how to guarantee abx resistance but, in my situation, the alternative is too dangerous.

Apologies if this isn't the right place to ask this question but the last Lyme Post was from a while ago and I wasn't sure if you would see it if I posted there.

Kind regards.

Anonymous said...

"Treatment with antibiotics kills all of the sensitive bacteria and leaves only the resistant. Thus, antibiotic treatments select for antibiotic resistant bacteria."

A sincere thank you for putting it so concisely.

3nod maka said...

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