Antibiotics, Gut Flora, Food Intolerance and Disease

Cattle Are Finished by Selective Killing of Gut Flora.  The Sickened Animals Store Fat that Grills Great.  People Get Metabolic Syndrome.

The likening of modern humans to potatoes sacked out on a couch is misleading.  The obesity epidemic linked to diets of processed foods more closely resembles the stumbling progression of cattle to abattoir.  Antibiotics and diet systematically lead in both feedlot and food court to gut dysbiosis, immune system failure, hormone disruption, rampant fat accumulation, physical inactivity, depression and the modern suite of chronic diseases.  Healthcare costs escalate, but vet bills, in contrast, are forestalled by a captive bolt pistol.

Background Observations

• Antibiotics kill bacteria and not humans, because the bacteria have different machinery for making proteins, nucleic acids and cell walls.
• Antibiotics kill bacterial pathogens and not viruses or fungi.
• Antibiotics kill helpful bacteria in the gut (gut flora) even more readily than pathogens.
• Antibiotics are used in meat production to alter gut flora to change animal metabolism;  e.g. cattle treated with antibiotics gain fat.  Protection from disease is secondary.
• Simple diet means simple gut flora.  Processed foods are simplified foods that simplify gut flora.
• Probiotics can replace only a small fraction of the gut flora diversity.
• Gut bacteria control the immune system development in the lining of the gut.
• Chronic antibiotic use permanently simplifies gut flora and compromises the immune system.
• The appendix stores gut bacteria as a reserve to replenish gut flora following diarrhea.
• Diseases based on inflammation and immune system intolerance result from gut dysbiosis (inadequate gut bacteria).

Antibiotics Kill Good Bacteria

This is a rant about antibiotics, not about humane actions.  Humane actions are not the point here, since I am talking about health care and not treatment of agricultural animals.  I am pleading for the rights of gut flora everywhere and antibiotics are the casual killers.  Compromised gut flora is collateral damage in attempting to eliminate bacteria characterized as pathogens.  Every time the pediatrician treats the mother by acceding to her pleas for an antibiotic prescription to silence a howling ear ache and get a good night’s sleep, or the dermatologist treats teen acne with antibiotics, billions and billions of domesticated bacteria die.

Constipation Is a Sign

Countless hours are wasted waiting, because antibiotic-depleted gut flora cannot hydrate and form normal stools.  Probiotics are gulped down, but they supply only a handful of the hundreds of bacterial species that are needed for health.  Yeasts and other fungi that are naturally resistant to antibiotics quickly replace the lost beneficial bacteria in the gut, vagina and on other body surfaces.  Surcease for simple sorrows leads to lingering and lasting laminations.  Don’t mess with mother nurture.

Damage of Antibiotic Use Is Slow

Most of the impact of antibiotic annihilation of bacteria normally present in humans is unobserved, because the deleterious effects lag months behind the initial treatment.  After all, cattle treated with antibiotics to restructure their gut flora to induce bovine obesity, appear to thrive as they rapidly gain weight and avoid symptoms of infectious diseases.  Humans on antibiotics also display fewer dental and incidental infections.  Constipation is not a high price to pay for a better mirror image.  

Antibiotics Compromise the Immune System

Unfortunately, allergies, autoimmune diseases, degenerative diseases and cancers are not usually linked to prior use of antibiotics.  There is no evidence that gut flora recovers  after antibiotic treatment, but constipation as a consequence of chronic antibiotic use is a common indicator of gut dysbiosis, collapse of normal gut flora bacterial communities.  The harbingers of inflammatory and degenerative diseases are present, but are usually discounted, because they are a common consequence of the Western diet.

Food Intolerance Reveals Inadequacies in Gut Flora

Food intolerance is a sign of depleted gut flora diversity.  Gut flora have hundreds of genes that can break down a huge diversity of polysaccharides derived from plant cell walls.  Gut flora of Japanese who routinely consume kelp have specialized enzymes to hydrolyze unusual algal sulfated polysaccharides.  Essentially all of the polysaccharides in plant fiber can be consumed by bacteria in the anaerobic environment of the colon.  Inability of individuals to digest particular food components usually results from a deficiency of the gut flora and an indication of a history of dietary simplification and antibiotic use.  Lactose intolerance, for example, results from depletion of lactose-degrading bacteria from the gut flora and can be remedied by simply eating lactose with probiotics for a couple of weeks.  Gut flora can adapt, but they need persistent exposure to diverse, i.e. non-processed, food.

Antibiotic Allergies Are Natural

Allergies develop from a combination of inflammation and compromised immunological tolerance.  Inflammation heightens processing of antigens for presentation to the immune systems, whereas loss of immunological tolerance means that aggressive immune responses are inadequately controlled.  Thus, innocuous environmental molecules are incorrectly recognized as pathogen components.  Allergies to antibiotics, such as penicillin, make sense, because the antibiotic is used to treat inflammatory infections and the antibiotic treatment eliminates the gut bacteria that are needed to develop gut lymphocytes (Tregs) to produce tolerance.  Antibiotics lay the foundation for immune system dysfunction that is central to many chronic diseases.

Healthy gut flora and a healthy immune system require:

• avoidance of antibiotics
• systematic (not simply eating yogurt) rebuilding of gut flora following diarrhea or antibiotic use; lack of an appendix means gut flora reservoir is gone
• eating a variety of vegetables; avoiding processed food
• using herbs and spices
• don’t overdo hygiene; gut flora diversity derives from bacteria that you eat and those that rub off acquaintances
• eat seasonally to increase diversity

Suffering from Inflammation?

How do you know if your symptoms result from inflammation?

My interest is the molecular basis of inflammation, how inflammation is triggered and how inflammation contributes to numerous diseases. I try to expose the inflammatory underpinnings of various diseases by initially linking a disease to inflammation and then unraveling the molecular events that lead to and make up the disease.

How Do I Link a Disease to Inflammation?

My first task is to check the biomedical literature to see if there are research articles that support anti-inflammatory interventions that prevent or limit the disease. I just do a PubMed search the disease name plus anti-inflammatory treatments, e.g. omega-3 fish oils, vitamin D, NSAIDs, etc. It is also possible to see if a disease, such as diabetes, that produces chronic inflammation is a risk factor for the new disease being examined. It is shocking to me that omega-3 fish oils (EPA/DHA) or even flax seed oil, have been found to be effective treatments for numerous diseases that range from allergies, arthritis, inflammatory bowel diseases, depression and even septic shock and multiple organ failure. Aspirin has been used to treat infertility and post partum depression, and at high levels to treat cancer.

Dietary Suppression as Prima Fascia Evidence of Inflammatory Cause

If I find that omega-3 oils have been used successfully to treat a disease, then I attempt to link inflammation to the molecular events that initiate the disease. The biomedical literature is of minimal help here. [Biomedical research is usually limited to assessing the impact of drugs on the symptoms of diseases, so the biomedical literature typically does not provide information on the cause of diseases or ways to cure diseases. Causes and cures do not receive research funding.] I have to learn the basic workings of the organs involved and the alterations of function associated with the disease. I have also found by long experience, that major molecular components are systematically missing from typical explanations of function.

Heparan sulfate/heparin Is Missing in Action

Heparan sulfate proteoglycans (HSPGs) dominate the extracellular environment and yet they are systematically excluded from biomedical research. On this blog, I have provided dozens of examples of the essential role played by HSPGs and disruption of these roles by heparin. The majority of cytokines, growth factors, clotting events, complement cascades and even lipid transport (LDL) act via HSPGs. Leaking of proteins into the urine, across the intestines or the blood brain barrier is controlled by HSPGs, is reduced by inflammation and can be partially repaired by heparin. Autoimmune and allergic diseases are initiated by disruptions in HSPG metabolism. Viral and bacterial pathogens bind to human cells via HSPGs. Cancer cells reduce their HSPGs and start to secrete heparanase in order to metastasize. Mast cells secrete heparin! HSPGs and heparin are major players in tissue function and yet the major cell biology text book does not even discuss them. HSPGs are not mentioned in medical school training even though heparin is the most commonly administered drug.

One of the insights that I bring to my conceptualization of diseases is the role of heparan/heparin in cellular physiology. It explains a lot.

Check for Inflammatory Symptoms by Trying the Anti-Inflammatory Diet

If your symptoms are due to inflammation, there is an easy way to find out. Since diet is the biggest source of inflammation and most of the cells of the immune system congregate in your intestines, it makes sense to check to see your health problems are rooted in inflammation by making simple changes in your diet. Since this is just a test, don’t worry about whether or not this is diet for the rest of your life. Just stick to it for a week and see if it changes your life.

The Basic Anti-Inflammatory Diet and Lifestyle Guidelines are here.

(Vitamin D and omega-3 fish oil amounts are minimal levels. More severe examples of inflammation will require higher levels. Vitamin D up to 10,000 IU per day has been found safe. Some individuals require up to 12 fish oil capsule per day to experience relief from symptoms. Increases should be gradual over weeks of time.)

Try it for a week and let me know if your symptoms disappear. The prevalence of diet-based inflammation, makes me confident that you will be glad that you tried these simple, healthy changes. For immediate relief of pain, see my articles on capsaicin, castor oil and menthol/Vicks.

This is not medical advice and is used only in appropriate support of primary medical care.

Prostate, Prostatitis, Cancer, Causes and Cures

Prostate problems are pervasive, and progressive in the U.S. -- approximately a quarter of a million prostate cancers are diagnosed each year. Chronic inflammation due to age or diet enhances prostatitis and cancer.

Prostate Surrounds Male Urethra

The prostate is a sexual organ. It responds to sexual stimuli, both physical and hormonal, and as a consequence is vulnerable to the same hazards: infection, inflammation, cycles of elaboration and cancer. The prostate straddles the male urethra and inflammatory swelling of the prostrate can strangle the flow of urine from the bladder. The prostate contributes part of the seminal fluid and backward flow of bacteria from the urethra into the prostate can be a source of infection.

Prostate Cells Require Testosterone for Growth

The prostate tissue responds to testosterone. The ebb and flow of testosterone, associated with sexual activity, results in increased production of prostate fluid containing proteins and other components that enhance performance of sperm in the female reproductive tract. The bottom line here is that prostate tissue and derived prostate cancer, responds to testosterone. For this reason, prostate cancer treatment has been based on blocking testosterone stimulation by removal of sources of testosterone and blocking testosterone receptors.

Testosterone Starvation Is Prostate Cancer Treatment

Testosterone, estrogen and vitamin D receptors are all cytoplasmic and the hormone/receptor complexes act as transcription factors to alter nuclear gene expression. It would be expected that prostate cancer, as well as breast, cervical, ovarian, testicular, etc. will respond in a complex manner to steroid hormones, including androgens, estrogens and vitamin D.

Cancer Requires NF-kB Activation

The common biochemistry supporting all cancers is inflammation that is required for proliferation in tissue. Central to inflammation is the transcription factor NF-kB. Inhibitors that block the activation of NF-kB also stop cancer. Most of these blockers are effective against cancer cells grown in culture flasks, because the inhibitors are taken directly into the cells and make contact with NF-kB (or stabilize the NF-kB inhibitor IkB.) Curcumin from turmeric, is one of the most potent inhibitors of NF-kB activation. It is very effective in cultures, but is only modestly effective against inflammation when eaten.

It is difficult to treat secretory tissues, such as prostate, breast, uterus, etc., because much of the tissue is separated from the blood circulation. Thus, infections in these tissues are harder to treat with antibiotics.

Prostatitis Results from Urinary Infections

The prostate is prone to chronic infections. Thus, urinary tract infections (UTIs) can lead to prostate infections (prostatitis). These chronic infections can contribute to chronic systemic inflammation. One symptom of chronic inflammation is depression (treated with SSRIs, antidepressants) another symptom is premature ejaculation (also treated with SSRIs.) Prostatitis-based inflammation can also set the stage for cancer.

Transglutaminase Autoantigen

Autoimmune diseases are also associated with chronic inflammation. One of the common autoantigens in autoimmune disease is tissue transglutaminase (tTG). Celiac is a classic example of the involvement of tTG, since tTG acts on the glutamine amino acids of gluten and converts them into glutamic acid residues. In the process tTG becomes covalently attached to the gluten. The strong heparin binding domains of tTG also facilitate its uptake and processing as an immunogen under inflammatory conditions and result in antibody production to both tTG and gluten. Anti-tTG antibodies and inflammation can also lead to attack on other tissues, such as the thyroid and skin, leading to a variety of celiac-associated autoimmune conditions.

The prostate produces its own transglutaminase. I think it is likely that prostatitis in some cases progresses to an autoimmune disease and prostate transglutaminase is a likely candidate for one of the autoantigens involved. This also predicts an association with celiac and a requirement for chronic systemic infection with a likely elevation of C-reactive protein and inflammatory cytokines (IL-1, IL-6, TNF). Deficiency of vitamin D and omega-3 fatty acids are probably major contributors. Increased risk attributed to consumption of a high fat diet and meat, is probably actually due to inflammation from a high carbohydrate diet and high omega-6 vegetable oils (or perhaps corn-fed meat.)

Protect Prostate with Anti-Inflammatory Diet

Prostate problems are frequently assumed to be a natural result of advancing age, but they are actually symptoms of mismanaged chronic inflammation. Men should not just stand and wait for prostate problems.

Avoidance and treatment of prostate problems seems to be an obvious application for an anti-inflammatory diet and lifestyle.

Cure Acne, Back Pain, Tendonitis, Depression

Remedies Include Vicks Vaporub, Castor Oil and Anti-Inflammatory Diet

Simple anti-inflammatory treatments cure some of the most common health complaints. The big question is why people tolerate the problems rather than applying the readily available remedies.

It seems to me that one reason people don’t simply live anti-inflammatory lives and avoid health problems is that attacking the underlying inflammation by approaches that would have prevented the health problem in the first place, is inadequate for fixing the problem after it becomes established.

Health problems based on inflammation may have many different sources of inflammation. Many dietary deficiencies, for example, contribute to inflammation, so what we eat or don’t eat is a major health risk. Other common contributors to inflammation are dental cavities/infections and inadequate exercise.

Common Symptoms of Chronic Inflammation: Acne, Back Pain, Tendonitis, Depression

I have started to ask casual acquaintances if they have any aches or pains, because eliminating dietary sources of inflammation will be evident in relief of these problems. Common complaints are sore joints and tendons related to repeated use. An example is my barber who complained of pain in all of the tendons used to raise his arms to cut hair. Another friend just had her second child and suffered from shooting pains in the tendons of the arm she used to cradle the youngest when she used the other arm on some task.

Simple Anti-Inflammatory Diet Adjustments Get Quick Results

In many cases, a simple change in diet can lower chronic inflammation enough to provide relief from symptoms. Vitamin D deficiency is probably an underlying source of inflammation of most people in the US. So a simple supplement of 2000-5000 IU per day will have noticeable, anti-inflammatory impact on most people.

I recommended vitamin D and fish oil supplements to a friend suffering from chronic back pain. The back pain persisted, but his acne resolved. He stopped taking the supplements, but after physical therapy relieved the back pain, he returned to the supplements as an acne treatment. Now he has long term relief from all of his pains.

Elimination of Dietary Inflammation May Not Resolve Inflammation Based Health Problems

Health problems that start from aggrevated inflammation, may not be eliminated with resolution of the initial cause. My friend’s back ache, for example, didn’t respond to just elimination of deficiencies in his diet. It seemed that the back problems were self-sustaining. After he did exercises to remove the physical aggravation of his back, lack of dietary inflammation prevented the return of the back ache.

Complex Inflammatory Webs

A student of mine suffers from celiac. This is a complex autoimmune disorder of the intestines that is triggered by wheat gluten and is self-perpetuating. Of interest in this context is that celiacs frequently also have back problems. This indicates that the inflammation of the disease is systemic and impacts other tissues. Clearly, reducing dietary inflammation can go only so far in relieving this complex web of reinforcing sources of inflammation.

Simple Anti-inflammatory Interventions

My friend with tendonitis from holding her child got immediate relief from topical application of castor oil and dietary supplements eliminated the problem. Castor oil and capsaicin react with skin heat-sensing neurons to initiate an anti-inflammatory response in adjacent tissue. In a similar way, menthol acts on cold-sensing neurons and relieves pain by reducing inflammation. Vicks Vaporub is a common commercial source of menthol (other sources are blue Listerine mouthwash and Noxema lotion), which give faster relief than longer lasting castor oil for many connective tissue/joint aches. Exercise is another source of relief for inflammation-based aches and pains.

Health: Combinations of Interventions and an Anti-Inflammatory Diet

Anti-inflammatory drugs, such as aspirin, disrupt the molecular signals that produce inflammation and result in relief from inflammation and pain. The common ailments discussed here respond to anti-inflammatory drugs. Depression was mentioned to point out the psychological dimensions of inflammation. Reproduction/birth is controlled at many points by the processes that we call inflammation and the most inflammatory stage is birth. It is not surprising that disruption of the normally rapid resolution of inflammation following birth leads to postpartum depression. It is surprising that postpartum depression can be relieved by anti-inflammatory drugs.

Fighting Inflammation-Based Diseases

Complex diseases such as allergies, asthma, arthritis, vascular/heart diseases, inflammatory bowel diseases, cancers, etc. are all based on chronic inflammation, but they are also self-reinforcing inflammatory diseases. Cures will require elimination of sources of chronic inflammation, e.g. diet, plus disruption of the disease-supporting inflammation, e.g. food/gut flora-stimulation of inflammation of the bowel.

Fundamental to the cure of all diseases is a supporting anti-inflammatory diet and lifestyle.

Is a Belly Bad?

A protruding midsection can mean many different things. It can be obesity, starvation/kwashiorkor or sarcopenia. It can mean there is a layer of fat outside, sagging organs poorly supported by weak abdominal muscles or fat surrounding the organs and stretching the muscles outward.

Alternatively having the same “lean” profile at 60 as at 16 could be a sign of a decline of muscle and an increase in fat surrounding organs. You can always have a porthole put in to see what is going on, or you can check the calendar and your C-reactive protein level.

If you are over fifty and your doctor has told you that your CRP, a measure of inflammation, is starting to creep up, then you are starting to suffer from age-related loss of muscle, sarcopenia. That is, you have begun to replace your muscle mass with fat, and the fat is producing inflammatory signal molecules, cytokines, that are the same as those produced by your immune system cells in response to an infection.

Most of the symptoms we associate with aging are just poorly managed chronic inflammation, as a result of replacing muscle with fat. The fat is metabolically lethargic, so you actually need less food, as your muscle mass declines. The result is that it is progressively easier to put pounds on. That is the bad news. The good news is that building muscle requires at least one of the inflammatory cytokines produced by fat, IL-6, so gaining muscle should be easier until you get back into shape. Losing weight is also anti-inflammatory, if the loss is fast enough to produce a fasting physiology.

All of the diseases associated with increasing age are just the accumulation of problems that result from increasing levels of chronic inflammation. Most of the increase is the result of inflammatory diet, but the increasing inflammation also decreases the desire to be physically active, with the result being a loss of muscle mass. Adjustment to an anti-inflammatory diet and lifestyle, can reverse the aging process.

It is also possible to be physically active and have a youthful muscle mass, but still have an inflammatory diet. The result will still be chronic inflammation, and cryptic inflammatory diseases that accumulate with time and produce sudden failures of joints, coronary arteries or cancer. Estrogens are also naturally anti-inflammatory, so women will find that menopause reveals any inflammatory diet/lifestyle that has been hormonally camouflaged. Thus, menopause may produce any of the typical signs of inflammation, e.g. acne, depression, back problems, arthritis, etc.

The bottom line is that a weak gut and/or extra body fat will cause problems at any age. And at any age, the diseases that are associated with inflammation can be minimized or avoided by an anti-inflammatory diet and lifestyle/exercise.

Inflammation Causes Disease

Human diets have changed dramatically over the last few hundred years, and as a consequence so have our diseases. The most recent shift in diet over the last hundred years has resulted in a shift from infectious diseases to degenerative diseases. This trend is summarized in the following Wikipedia entry.

Lifestyle diseases, from Wikipedia:

"Lifestyle diseases (also called diseases of longevity or diseases of civilization) are diseases that appear to increase in frequency as countries become more industrialized and people live longer. They include Alzheimer's disease, atherosclerosis, asthma, cancer, chronic liver disease or cirrhosis, Chronic Obstructive Pulmonary Disease, Type 2 diabetes, heart disease, nephritis or chronic renal failure, osteoporosis, acne, stroke, depression and obesity.

Death statistics in the United States
In 1900, the top three causes of death in the United States were pneumonia/influenza, tuberculosis, and diarrhea/enteritis. Communicable diseases accounted for about 60 percent of all deaths. In 1900, heart disease and cancer were ranked number four and eight respectively. Since the 1940s, the majority of deaths in the United States have resulted from heart disease, cancer, and other degenerative diseases. And, by the late 1990s, degenerative diseases accounted for more than 60 percent of all deaths.
Reference:
National Center for Health Statistics, National Office of Vital Statistics, 1947 for the year 1900 (page 67), for the year 1938 (page 55)."

My point here is that all of the so-called lifestyle diseases are also based on inflammation. I checked the research literature for studies of the response of each of these diseases to diets supplemented with omega-3 fish oils. Studies had been performed in each case. Reduction of inflammation by fish oil treatment was uniformly effective in reducing symptoms of all of the degenerative diseases. Other diseases that can be added to the inflammatory list are spinal disc problems and hypertension. It is interesting that disc dislocations are associated with coeliac, an inflammatory/autoimmune disease. It is also interesting that acne and depression are listed. Acne is indirectly associated with diet, but if sufferers shift to an anti-inflammatory diet, acne symptoms disappear. Depression associated with childbirth is particularly responsive to anti-inflammatory drugs, diet and exercise. Most of the symptoms associated with aging are just due to inflammation and are similarly responsive to anti-inflammatory lifestyle changes

To summarize:

• Modern degenerative diseases are caused by modern inflammatory diets (and insufficient exercise.)
• Anti-inflammatory diet and lifestyle reduce degenerative diseases.
• Aging is predominantly mismanaged inflammation.
  

Depression

Your Diet is Depressing

It is no wonder that Americans are depressed. Workers are depressed. College students are depressed. Kids are depressed. New mothers are depressed. And they are all medicated with ineffective anti-depressants. It is an increasing epidemic of poor mental health care.

What is not uniformly recognized is that depression is a symptom of chronic inflammation. Moreover, the same diet changes that help with other degenerative and autoimmune diseases, also help with depression. There was a recent research article that found that postpartum depression in new mothers responded to anti-inflammatory drugs.

I am, of course, dealing in sweeping generalizations here and I explicitly am not attempting to replace medical evaluation in particular cases. There are many different kinds of depression. I just think that the impact of diet on mental health is depressingly ignored.

An evaluation of more than 250 studies on the usefulness of omega-3 oils in the treatment of many different mental health problems, including depression, observed conflicting results. One of the major problems with the studies, was that the researchers did not control the amount of omega-6 oils in the diets of the participants. Since it is the ratio of omega-3 to omega-6 oils in the diet that is important in controlling inflammation, this is a shocking mistake. The researchers seem to have been assuming that the omega-3 oils were treating a deficiency, instead of inhibiting the production of inflammatory prostaglandins from the omega-6 oils.
I think that most of the public dietary guidelines get it wrong, because they focus on reducing saturated fats. Replacing saturated fats with omega-6 unsaturated fats, e.g. corn oil, will lead to chronic inflammation. I don’t think that there is any good research that shows that there are health risks for saturated fats in your diet, unless you are in a chronic inflammatory state -- if you already exhibit the metabolic syndrome, then saturated fats are a double whammy.

It would seem obvious that anyone seeing a physician for depression, should be advised to shift to an anti-inflammatory diet. I think that the shift in diet will have greater impact than antidepressants. The first step is to ban trans-fats, high fructose corn syrup and omega-6 rich vegetable oils from the kitchen. Try to only use olive oil. The second step is to increase omega-3 oils by eating fatty fish and supplementing with fish oil capsules. I recommend an experiment to gradually increase omega-3 oils in your diet until you see relief from your depression. Each week keep track of how you feel each day. Starting with four fish oil capsules per day, increase each week by two more capsules per day, e.g. week 1 - 4 caps, week 2 - 6 caps, week 3 - 8 caps. The upper limit is probably about 12 caps/day. It will be harder if you are obese, because fat cells are inflammatory. Digestion of the oil is improved when eaten with other fat-rich foods. The capsules can be spread over several meals.

The bottom line: depression can result from chronic inflammation that has spilled over to become inflammation of the brain. Treating the chronic inflammation by correcting diet should reduce the symptoms of depression. It has been my observation that depressed people seem to benefit from gaining control of some part of their lives, so changing diet may be a good place to start.