Common Medicines Make Superbugs, Not Prescription Antibiotics

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Careless prescriptions and cattle fattening antibiotics are blamed for the rise of superbugs resistant to everything in the hospital arsenal, but that’s all wrong.  Antibiotics fail, because we are all abusing common medicines that also have powerful antibiotic activity.  All painkillers, anti-inflammatories, statins, antidepressants, and the whole list of common pharmaceuticals are the problem.  We simply use too many drugs.

Common drugs should also be labeled as antibiotics, because they kill the sensitive bacteria in your gut and leave behind just the resistant bacteria.  Unfortunately, the genetic mutations that make your gut bacteria resistant to drugs, also provide resistance to antibiotics needed to stop infections and that broad resistance to antibiotics can spread to pathogens that then become the dreaded superbugs.

Here are the simple facts that I have discussed at length in another post:

• Statins were antibiotics that were repurposed to lower LDL, “bad cholesterol.”

• Aspirin was an antibiotic that was shown to relieve pain and inflammation.

• Metformin was an antibiotic that later proved useful for treatment of diabetes.

• Many chemotherapy drugs are antibiotics developed for cancer treatment.

• Diuretics were antibiotics that indirectly reduce blood pressure.

• Antidepressants, such as Prozac, Zoloft, etc. are antibiotics.

Common Drugs Are Actually Antibiotics

Most pharmaceuticals are derived from phytochemicals, a.k.a antioxidants, adapted in plants to kill microorganisms, i.e. as natural antibiotics.  It is not surprising that drugs = antibiotics.  What is surprising is that people assume that if antibiotics are labeled with some other activity, that they cease to be antibiotics.  All drugs are also antibiotics and that is why a major side effect of most medicines is upset gut bacteria.

Overuse of Common Drugs Produces Superbugs

Simply put, common medicines you swallow, kill bacteria in your bowels.  Some bacteria survive and are called “drug resistant.”  Bacteria accumulate resistances to several different kinds of drugs and are called “multidrug resistant.”  As might be expected, hospitals are the breeding grounds for multidrug resistant, mutant bacteria of all different types.  Unfortunately, anyone who takes several types of medications is also a source for multidrug resistant bacteria, so nursing homes are the most frequent sources of superbugs that cause outbreaks of hospital infections.

The Only Way to Stop Superbugs is to Use Less Drugs

The bottom line is that even if doctors start to use antibiotics more rationally and antibiotic use in agriculture is eliminated, superbugs will still be a big problem, because they will be produced by excessive use of common drugs, i.e. those found on the shelves of drug stores and supermarkets, as well as prescribed by doctors.  

The only solution to the superbug problem is to reduce pharmaceutical use by 99%.

Making Monsters, Renegade C. butyricum and E. coli

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Clostridium

It is common knowledge that our gut is teeming with good bacteria that we feed with prebiotic fiber to keep us healthy.  But a sick gut, caused by antibiotics or fiber deficient processed food, can make us susceptible to infection with pathogens, such as the notorious, toxin-producing strains of E. coli that cause food poisoning or Clostridium difficile, a.k.a. C. diff. of hospital infections.  What prompted me to write this post, was reading that premature babies in neonatal intensive care units are dying from gut infections caused by a pathogenic strain of C. butyricum, known as a probiotic that provides protection from C. diff.

Healthy Gut Microbiota

New Toxin-Producing, Antibiotic Superbugs are Manmade

Closer examination of the report revealed that the new strain of C. butyricum is a toxin producer.  This made a lot of sense to me.  When I started working with E. coli in the early 70’s, it was known as the safe ubiquitous lab bacterium that everyone cultivated in their colons.  Similarly, C. butyricum is present in commercial probiotics and is a hero for producing butyric acid from resistant starch, promoting immune system development and reducing inflammation.  How did these beneficial gut bacteria become converted into pathogens?

Source of Antibiotic Resistant Superbugs

Antibiotic and Drug Use in Hospitals and Farms Select for Antibiotic Resistance

C. butyricum and E. coli have been converted into toxin-producing, antibiotic resistant pathogens by common procedures of meat production and hospital treatments.  These bacteria do not normally produce toxins nor are they resistant to antibiotics.  They have been systematically selected for those pathogenic properties.

Formula Contributes to NEC

Common Practices in Neonatal Intensive Care Units Lead to NEC

Chronic inflammation is one of the common contributing factors to premature births, because labor is stimulated by a spike of inflammation, normally occurring at 40 weeks of gestation.  Chronic inflammation from autoimmune disease, infection, or obesity, can cause labor to be early and a newborn to be unprepared for life without some special care.  Unfortunately, there is not uniform enlightenment about the development of newborn gut flora, and immature newborns are exposed to antibiotics and formula, which prevent normal gut flora development.  C. butyricum is not present in low birth weight babies exclusively fed breast milk, but the combination of antibiotics and formula select for colonization by antibiotic resistant hospital strains of C. butyricum.  This sets the stage for necrotizing enterocolitis, NEC, which is as nasty and lethal as the name suggests.

Toxin Producing E. Coli are Manmade

Antibiotics Used to Make Fat Cattle Select for Toxin Production

The development of toxin producing E. coli in cattle suggests how pathogenic C. butyricum was produced in the hospital environment.  E. coli was a healthy component of the digestive system of cattle, until the gut flora community was reengineered by antibiotics, so that short chain fatty acids that were normally converted into more gut bacteria and more steer manure, were instead absorbed by the gut to produce a fatter steak.  Unfortunately, this newly designed gut flora community left no place for E. coli.  Some of the E. coli spontaneously mutated to antibiotic resistance and/or picked up multi-drug resistant plasmids from other bacteria, but that still didn’t provide a niche in the new community.  Picking up a toxin-producing gene solved that problem, because the toxin releases needed nutrients from host cells.  Thus, antibiotic use in cattle directly selected for the evolution of toxin-producing, antibiotic resistant E. coli.

Antibiotics and Formula Use Lead to NEC Bacteria

Toxin-producing C. butyricum would be expected to develop in the hospital environment, because high antibiotic use will select for multiple drug resistant C. butyricum, and the disrupted gut flora produced in the presence of antibiotics will also favor toxin producing strains.  Thus, the hospital environment selects for toxin-producing, multiple drug resistant C. butyricum.  The gut flora of newborns in a neonatal intensive care unit are acquired from the staff and relatives that handle the babies.  Since the babies are routinely treated with antibiotics and drugs, multiple drug resistant bacteria, including C. butyricum, are common in fecal samples of neonates and persist for at least two years. 

Breastmilk Prevents NEC in Newborns

Breastfeeding or Donor Bank Milk Avoids NEC Caused by Formula

Exclusive use of breastmilk from mothers, donor banks or breastmilk products, eliminates NEC.   Some hospitals respond to the scientific evidence and use only breastmilk for newborns.  Other hospitals simply stick to old practices until law suits force them to change.  They continue to use formula and cow’s milk products,  even though breastmilk is available, and as a consequence NEC is still a problem. Prejudice against breastmilk persists and there is intense promotion of commercial alternatives that contribute to NEC.  None of the alternatives containing probiotics and prebiotics have been found to be adequate.   Hospitals are slow to change, because patients are uninformed and low birthweight babies continue to die.

Gut Microbiome 2014: Diet, Inflammation, Disease, and Repair

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The year 2014 began with my posts on damage to the gut microbiota caused by antibiotics, processed foods and excess hygiene.  I lamented the inadequacy of information from the media on damage/repair of the gut bacteria and highlighted medical myths with a post on some of Dr. Oz’s own ills that are self-inflicted by his diet and hygiene recommendations.  I also started to discuss how to cure autoimmune diseases by repairing damaged gut flora and by avoiding the antibiotic activity present in many common drugs.

With my 200th post in March, I summarized my thoughts on the causes and cures of common diseases in a series of diagrams on:

Health Diagram I    — Gut Flora and Diet, 

Health Diagram II   — Curing Autoimmunity and Allergies,

Health Diagram III  — Inflammation from Cell to Tissue  

I illustrated the relationships among diet, inflammation and diseases mediated by gut flora that I have discussed, since I started my blog in 2008.  Now after a couple of hundred articles and more than two million visits to my blog, I think that I am starting to grasp some of the major issues that cause inflammatory diseases.  The cures also now seem obvious.

Antibiotics Contribute to Autoimmune Diseases

Some species of gut bacteria are needed for the development of the aggressive half of the immune system and other species are needed for the suppressive half.  Thus, starving or poisoning gut flora leads to immune system problems and diseases.  Antibiotics are a quick way of crippling the immune system.  It seems that the aggressive part of the immune system is less fragile, because in most cases antibiotic treatments produce autoimmune disease due to loss of bacteria that are needed for development of immune cells that block the aggressive half of the immune system from attacking innocuous cells of the body or environment, i.e. antibiotics usually trigger deficient tolerance, and autoimmunity.

Feed the Gut Microbiome for a Healthy Immune System

Diet provides food for the body and flora.  Protein and fat are the macronutrients needed for the body, while the gut microbiota lives off of plant polysaccharides (except starch) that pass through the small intestines undigested into the colon.  The hundreds of plant polysaccharides are hydrolyzed by hundreds of enzymes made by gut flora and produce short chain fatty acids, e.g. acetate and butyrate, that feed colon cells.  Food processing systematically removes polysaccharides that feed gut flora and compromises the components of the immune system dependent on those bacteria.

Repairing the Gut Microbiome by Eating the Missing Bacteria

It is easier to see that eating a diet that lacks food for the gut microbiota will be a problem, than it is to figure out where to find replacements for lost species of gut bacteria.  The only way that bacteria get into the gut is down the throat.  To repair a damaged gut microbiota requires both changing diet and introducing the missing types of bacteria by eating them.  Eating dairy probiotics and fermented vegetables can provide a quick, but only temporary fix.  Most of the needed bacteria are more common in soil than in food.

Phytochemicals Are First and Foremost Antibiotics

I was shocked that my background in phytochemicals didn’t lead more directly to a major culprit causing modern diseases.  The gut microbiota is clearly a major factor in health and sickness.  Antibiotics that kill bacteria, damage the gut microbiota.  It is also unsurprising that processing food to reduce soluble fiber, damages gut flora, by systematically depriving gut bacteria of their major source of food.  The proliferation of antimicrobial products also damages the gut flora.  What I missed in this onslaught of modern lifestyles on the gut microbiota, was the major player in antibiotic resistance — phytochemicals are natural antibiotics. 

I Missed the Antibiotic Activity of Common Medicines

I studied phytochemicals and wrote research articles on their toxic, antibiotic activities, but everyone else was merchandizing phytochemicals as antioxidants, essential oils and superfoods.  This is a major conceptual problem.  Our bodies expend a significant fraction of our energy resources to detoxicify phytochemicals and human cultures have elaborate rituals to avoid phytochemicals and domesticate plants by breeding for the least toxic.  What I missed was the implication that the pharmaceutical industry was repurposing toxic, antibiotic phytochemicals as medicines and then skipping the "antibiotic" label.

Unlabelled Antibiotic Drugs Cause the Rise of Superbugs

Overuse of antibiotics is a problem, because it damages the gut microbiome and contributes to the modern increase in autoimmunity.  Food processing is another culprit and so is the mania for hyperhygiene and the demonization of bacteria.  Unfortunately, the major culprit in the development of multiple antibiotic resistant superbugs is the tons of commonly used pharmaceuticals that systematically attack gut bacteria, but are not labelled as antibiotics.  Most modern drugs were developed from phytochemicals and were initially used in plants to kill bacteria and fungi, i.e. phytoalexins.  Pharmaceutical companies acknowledge the antibiotic activities of common drugs, by sponsoring research conferences to develop existing drugs as new classes of antibiotics for treatment of superbugs.

Antibiotic Resistance, Superbugs and Drugs

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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.

Health in Diagrams

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.