Dec
03
2022

The Bubonic Plague Still Affects some People today

Although the plague is of historic significance, it still is around and the Bubonic plague still affects some people today. In the Middle Ages the world population experienced a reduction from 475 million to 350–375 million between 1346 and 1353. This pandemic relied on fleas on ground rodents, which showed infection with the bacterium Yersinia pestis. Flea bites transmitted the plague bacteria to humans. Nowadays we have effective antibiotics against the plague. Doxycycline is the antibiotic of choice against this bacterium. But in the Middle Ages no antibiotic was available. Those who had a certain variant of the immune system survived, while others who did not have this perished.

Study from nature showing changes of the immune system due to the Bubonic plague

An international research article involving scientists from Canada, the US and France was published in the medical journal nature. Nature published this on Oct. 19, 2022. The title was:” Evolution of immune genes is associated with the Black Death “. The scientists worked with a hypothesis that the human immune genome underwent a shift after the plague in those who survived. They tested their hypothesis by doing DNA analyses in corpses from before, during and after the Black Death. Specifically, more than 300 skeletons came from London/England, where the plague hit hard. 198 samples came from 5 different locations in Denmark. Researchers extracted DNA from the roots of the teeth. They checked for the individual’s’ DNA and for the presence or absence of the bacterium Yersinia pestis. CNN summarized this here.

Results of the study

Hendrik Poinar is a professor of anthropology at McMaster University in Hamilton and coauthor of this study. He said: “It’s a long process, but in the end you have the sequence of those genes for those people from before, during and after the plague and you can ask: Do the genes one population carried look different than the ones another population carried?” There was one particular gene, ERAP2 that had a strong association with the plague. The London study showed that 40% of individuals had an ERAP2 variant protective of the plague prior to the plague. After the plague 50% of the individuals had this variant.

Denmark data

In Denmark prior to the plague 45% of the population carried the variant of ERAP2, while 70% of the population buried after the plague carried this variant. The researchers did in vitro experiments with cultured cells. They could show that macrophages, which are immune cells that initiate immune responses, kill Yersinia pestis bacteria better when the ERAP2 variants are present in comparison to when they are not.

The downside of immunity

The downside of the ERAP2 variant is that researchers linked it to a greater susceptibility to autoimmune disorders. Diseases like Crohn’s disease, rheumatoid arthritis and systemic lupus belong into this category. Luis Barreiro is a professor of genetic medicine at University of Chicago and a coauthor of the study. He said: “This suggests that populations that survived the Black Death paid a price, which is to have an immune system that increases our susceptibility to react against ourselves.” He mentioned further:” It is unlikely that Covid-19 outbreak would shape our immune system in a similar way — largely because the disease predominantly kills people after their reproductive age, meaning it’s unlikely genes that confer protection would be passed on to the next generation.”

The Bubonic Plague Still Affects some People today

The Bubonic Plague Still Affects some People today

Conclusion

A publication in October of 2022 examined 300 skeletons from London, England where the plague hit severely between 1346 and 1353. The study also examined skeletons from Denmark. In both locations the scientists timed the samples before, during and after the pandemic. They found a genetic variant of the immune system by the name of ERAP 2, which changed in the population before and after the plague. The London study showed that 40% of individuals had an ERAP2 variant protective of the plague prior to the plague. After the plague 50% of the individuals had this variant. In Denmark 45% of the population carried the variant of ERAP2, before the plague while 70% of the population buried after the plague carried this variant. In vitro studies showed that macrophages were more aggressive as a result of sensitization of the immune system from an increase of the ERAP2 variant.

Autoimmune diseases

The increase of the ERAP2 variants stimulates the immune system. The researchers determined with in vitro studies that the Yersinia pestis bacterium stimulate macrophages. The downside of the ERAP2 variant is that researchers linked it to a greater susceptibility to autoimmune disorders. Diseases like Crohn’s disease, rheumatoid arthritis and systemic lupus belong into this category. Professor Luis Barreiro from the University of Chicago said:” It is unlikely that Covid-19 outbreak would shape our immune system in a similar way — largely because the disease predominantly kills people after their reproductive age, meaning it’s unlikely genes that confer protection would be passed on to the next generation.”

Sep
26
2020

A New Antibiotic Against Methicillin Resistant Staphylococcus aureus

A US study describes a new antibiotic against methicillin resistant Staphylococcus aureus. It is a lysin-based antibacterial agent.

Physicians have been looking for years for a solution regarding the increasing antibiotic resistance problem. But several attempts in the past have failed.

Staphylococcus infections are the most common bacterial infections of human skin, of soft tissue, joints, bones, and pneumonia. In addition, it can cause endocarditis (=infection of heart valves) and lead to blood poisoning (septicemia).

Staphylococcus aureus is the underlying bacterium behind staph infections. With the introduction of new antibiotics  it takes only 1 to 2 years before this bacterium learns to become resistant. Researchers noticed that the bacteria start to produce lysins and suddenly they are resistant to the latest antibiotic. Further research zeroed in on lysostaphin, which was active against resistant Staphylococcus bacterial strains.

Deimmunized lysostaphin

Lysostaphin is an antibacterial peptide described here in detail. But there still was some interference with immunologically active surface antigens that scientists were later able to overcome. Researchers succeeded lately in removing some of the surface antigens and develop deimmunized lysostaphin. This is what this publication is all about.

It describes how T cells cannot detect the surface antigen properties of deimmunized lysostaphin. This way none of the strength of deimmunized lysostaphin gets lost in the fight against resistant staphylococcus that normally form anti-drug antibodies. Researchers pointed out the importance of the deimmunization process to make deimmunized lysostaphin invisible to the T cells of the immune system.

Vigorous testing of deimmunized lysostaphin

The researchers who investigated the efficiency and safety of deimmunized lysostaphin did the following tests.

  • Although lysostaphin was deimmunized, it retained potent in vitro and in vivo anti-staphylococcal activity. In vitro studies involving Petri dishes with methicillin resistant Staphylococcus aureus showed the effectiveness of deimmunized lysostaphin. In vivo testing in a mouse and rabbit model also showed effectiveness.
  • Deimmunized lysostaphin showed reduced immunogenicity in vivo. Researchers tested this in mice and compared the results to regular lysostaphin, where there was a swift immunological response.

More points regarding deimmunized lysostaphin

  • Immune evasion allows for repeated efficient dosing of deimmunized lysostaphin. This means that the physician can administer the antibiotic (the deimmunized lysostaphin) to fight the methicillin resistant Staphylococcus aureus with several daily doses.
  • The deimmunization process allows deimmunized lysostaphin to evade the immune response that occurs to regular lysostaphin. This prevents future resistance development. It also prevents that the immune responses weaken the anti-methicillin resistant Staphylococcus aureus response.
  • Researchers showed in a difficult rabbit endocarditis model that deimmunized lysostaphin treats MRSA infection successfully. Endocarditis is an infectious disease, which is both difficult to treat in rabbits, but also in humans. For this reason, rabbits are often used as a model when new antibiotics are developed. If they are successful in the rabbit model they often get approval later for human treatments.

Deimmunized lysostaphin in humans

Unfortunately, we are still a few years away from using deimmunized lysostaphin in humans. After successful use of lysostaphin in mice and rabbits the next logical application is to launch human clinical trials. I am convinced that this will be the next step and very likely will be successful.

A New Antibiotic Against Methicillin Resistant Staphylococcus aureus

A New Antibiotic Against Methicillin Resistant Staphylococcus aureus

Conclusion

Researchers found a new antibiotic against methicillin resistant Staphylococcus aureus in a lysin-based antibacterial agent. This peptide has surface antigens that scientists had to removed to make it more effective. The end result was a deimmunized lysostaphin. Researchers tested this new antibiotic that is effective against many antibiotic resistant strains of bacteria successfully in mice and rabbits. The next step is testing in humans. This involves several phases of clinical trials. These clinical trials have to show that there is a lack of toxicity. In addition, they have to show that the new antibiotic is effective against resistant bacteria. I estimate that this process can still take about 5 years from now before the clinician can use this antibiotic routinely. As the new antibiotic is a polypeptide, it the patient cannot take it orally, as the gut is digesting it. The patient has to take it by injection.

Jul
04
2020

Probiotics and a Phage Blend for Digestive Problems

In general, probiotics and a phage blend for digestive problems can help patients with irritable bowel syndrome (IBS). It is important to realize that about ¾ of Americans suffer from digestive problems. They develop symptoms of gas, bloating, diarrhea and stomach pains. To put it another way, about 1 in 7 Americans suffer from the condition, called chronic irritable bowel syndrome. That is to say, he underlying problem is an imbalance of gut bacteria where the bad ones outnumber the good ones. There are a number or reasons why bowel flora gets disrupted. We eat more processed foods, less fiber, and beef products from industry farms contain antibiotic residues. In feedlots for beef cattle antibiotics are fed to the animals as growth promoters. The residues in the meat kill the good bacteria in our guts and the bad ones proliferate. This causes digestive problems, but also weakens our immune system.

How probiotics work

Probiotics can restore our gut flora to a large extent. But some of the probiotic action gets lost in the stomach from the acidic milieu. A recent publication from a panel of gastroenterologists has not supported the wide use of probiotics. They came to the conclusion that probiotics have not shown enough benefit to a number of clinical conditions. The researchers mentioned Crohn’s disease, C. difficile infection, ulcerative colitis and irritable bowel syndrome (IBS) in particular of not responding to probiotics. But this may be because of inactivation of some of the power of the probiotics by stomach acid. In addition, by not using phages to potentiate the probiotic action probiotics may fail to permanently to improve the gut flora. I have previously discussed the importance of probiotics for the gut flora.

History and use of bacteriophages

Bacteriophages are now often just called phages. Dr. Frederick Twort, an Englishman detected phages in 1915 during World War I. Essentially a phage consists of either DNA or RNA and a protein envelope around this. Phages are very specific for certain bacterial strains. They attach to the bacteria and inject their own DNA or RNA into the bacteria. This stops the bacteria from multiplying, but makes the bacteria produce many more identical phages. Phages are useful to control the growth of problem bugs including antibiotic-resistant bacteria. However, the regulatory agencies were slow to approve phages despite a good safety record. Life Extension Magazine recently published a review article about this subject.

Phages helping to protect probiotic bacteria

Phages naturally play a role in keeping the gut flora stable. In this lengthy review, published in January 2020 phage actions are reviewed. It also mentions the connection between the gut flora and the immune system. The Life Extension Magazine article mentioned above describes experiments that show the action of phages. E. coli is the main bacterium in the large intestine. It is also the bacterium that can cause pneumonia, diarrhea and urinary tract infections.

Experiments with bacteria and phages in Petri dishes

According to the Life Extension Magazine article researchers did experiments with Bifidobacterium longum, one of the desirable gut bacteria. This was placed on a Petri dish along with E. coli bacteria. In a second Petri dish Bifidobacterium longum, E. coli and a phage mix were placed. After 5 hours there was hardly any growth of Bifidobacterium longum in the first petri dish, as it was crowded out by E. coli. The result in the second Petri dish was interesting: the Bifidobacterium longum colonies were 7000-times higher in number than in the other Petri dish without the phage mixture. The phages had selectively attacked the E. coli bacteria, which made room for the Bifidobacterium longum bacteria to multiply.

Animal experiments with bacteria and phages

The Life Extension Magazine review mentions animal experiments with phages next. One group of mice received B. longum and the disease-causing E. coli in their food. The other group had the same bacteria plus a mix of phages directed against E. coli. For the phage group the results within 24 hours were as follows.

  • The E. coli count in the small intestine was 10-fold lower, in the large intestine 100-fold lower and in the fecal matter 100-fold lower.
  • The phage group also had a 100-fold increase of the B. longum count in the small intestine. The large intestine also had a 100-fold increase of the B. longum count. And there was a 40-fold increase of B. longum in the fecal matter.

Control mice without the phage mix developed constipation and intestinal segments showed redness, swelling and leaks. In contrast, the phage mix group of mice showed no side effects and had improved digestive function.

Human studies using probiotics and a phage blend for digestive problems

Safety tests of phage therapy were next in 2005 involving 15 volunteers. There were no side effects using two different phage concentrations to diminish E. coli. Researchers had done other safety experiments in Russia and in Poland in the past. Patients with ulcerative colitis responded with improved symptoms and improved endoscopic findings to treatment with two probiotics. They received fermented milk products (Cultura) containing live lactobacilli (La-5) and bifidobacteria (Bb-12) for 4 weeks. There were 51 patients with ulcerative colitis and 10 patients with familial adenomatous polyposis. Abdominal cramps, Involuntary defecation, leakage and the need for napkins were significantly reduced in both groups. An endoscopic score of inflammation showed a significant decreased when the baseline exam was compared to the exam after the 4-week intervention.

Literature review about phages

Here is a thorough review in a publication dated 2011, which describes research from Poland and other countries describing the action of bacteriophages, now simply called phages. It lists many human experiments and shows that phages are safe to use in humans.

Irritable bowel syndrome

Irritable bowel syndrome (IBS) presents with a pathological intestinal function, which can be quite disabling. Another name for it is “spastic colon”, because many patients complain of significant bowel spasms. Some health providers still use this alternative term. This syndrome is more common among women and there is a theory that female hormones may have something to do with the pathophysiology of irritable bowel syndrome. Testosterone on the other hand may have a calming effect on the gastrointestinal tract.

Symptoms and treatment of IBS

Generally speaking, irritable bowel syndrome occurs first in the teens or early twenties, but then frequently tends to become chronic. The patient chiefly complains of abdominal bloating and distension. Bowel movements lead to a marked relief of pain. There is often mucous in the stools. After a bowel movement there is often a feeling that the rectum did not empty entirely, even though it did. Food intake or stress can bring on these symptoms and they always occur during the waking period. At nights most patients have no pain.

Among other measures taking probiotics alone or mixed with phages can normalize the bowel flora. In older men IBS symptoms may indicate a reduction in testosterone production. If the blood contains a low testosterone level, the physician may want to replace the missing testosterone with injections or bioidentical testosterone creams. This can improve IBS in older males.

A safe delivery system for probiotics and a phage blend for digestive problems

Life Extension has developed a dual capsule that brings the inner content safely through the stomach and protects the mix of probiotics and phages from stomach acid. The capsule only opens in the small intestine where it releases its content of probiotics and phages into the gut. This allows the good bacteria like B. longum to multiply and suppresses E. coli, which would otherwise interfere with the beneficial bacteria.

Probiotics and a Phage Blend for Digestive Problems

Probiotics and a Phage Blend for Digestive Problems

Conclusion

About ¾ of Americans suffer from digestive problems. Many have a disbalance of the gut flora. But it is not easy to replace poor gut flora with a healthy one. Recent research showed that a combination of 7 probiotic strains with a mix of 4 E. coli fighting phages can give tremendous relief from bloating, diarrhea and abdominal cramps to patients with irritable bowel syndrome (IBS). Life Extension has developed a special dual capsule that “sneaks” the capsule through the stomach. It will only open in the small intestine. This way the content of the inner capsule with the mix of probiotics/phages stays safe from the stomach acid. At the end many more beneficial bowel-bacteria are growing in the small and large intestine. This normalizes the symptoms of the patient and leads to better digestion of food. Probiotics and phages are the new players in the gut microbiome.

Jun
27
2020

A New Antibiotic, Teixobactin Can Overcome Antibiotic-Resistant Superbugs

A new antibiotic, teixobactin can overcome antibiotic-resistant superbugs. The discovery of teixobactin took place in 2015. It is a peptide with 11 amino acid units. Teixobactin is derived from a gram-negative bacterium, Eleftheria terrae. It is the first of a new class of antibiotics that can kill superbugs. Two examples, for instance are methicillin-resistant Staphylococcus aureus and resistant Mycobacterium tuberculosis. Researchers have been battling with difficult solubility of teixobactin and problems synthesizing this peptide in the laboratory. Teixobactin binds to the membranes of the bacteria it fights. This is a new mechanism for this new class of antibiotics, different from conventional antibiotics.

Mechanisms of fighting bacteria resistant to conventional antibiotics

But it is exactly this quality that is necessary to fight the antibiotic-resistant bacteria. The researchers showed that teixobactin binds weakly to a component of the bacterial cell wall, called “Lipid II”. But they found a second mechanism, namely blocking precursors of cell membrane synthesis in the bacteria they fight. Because of these unique mechanisms it is possible for them to fight a multitude of bacteria resistant to conventional antibiotics. Teixobactin has a unique molecular structure, which makes it difficult for resistant bacteria to develop resistance to it.

Antibiotic resistance

Resistance to antibiotics is a worldwide problem. There are several factors that worked together to make antibiotic resistance such a big issue. For instance, in the past many doctors prescribed antibiotics for any viral cold, even knowing that antibiotics only work against bacteria. Aside from this, the agricultural practice of using antibiotics as a growth stimulator is also an important factor for antibiotic resistance to develop. It is the bacteria that become resistant, not the human body. Several clinical entities involving resistant bacteria exist that show the magnitude of the problem.

Flesh-eating disease

Necrotizing fasciitis (or flesh-eating disease) can develop when you swim in contaminated waters and the bacterium, Vibrio vulnificus enters through skin sores or wounds. The CDC warns that you should stay out of salt water or brackish water, if you have a skin wound. The flesh-eating bacteria, Vibrio vulnificus can become very aggressive, once it has entered the body. Right now, 1 out of 5 people who get infected will die and many people require ICU treatment. Others need limb amputations. All of this can happen within only 1 or 2 days of becoming ill. The hope is that with the development of teixobactin as an injectable medication or as an oral pill there will no longer be deaths, amputations and scarring due to this bacterium, as the antibiotic will very quickly eradicate Vibrio vulnificus. I have previously written about what hospitals can do to fight superbugs.

The most common antibiotic-resistant bacteria

Here is a brief review of the most common antibiotic-resistant bacteria.

Mycobacterium tuberculosis

Since the 1950’s and 1960’s tuberculosis was treatable with a combination of two antibiotics over a period of six months to two years. But in the last 10 years more and more resistant strains of tuberculosis have developed. This is called multi-drug-resistant TB. In 2013 statistics showed that 3.7% of newly diagnosed tuberculosis cases were multi-drug-resistant TB. Many of these cases can be traced back to prisons and homeless shelters.

Methicillin-resistant Staphylococcus aureus (MRSA)

MRSA has become a common resistant bacterium that can present with difficult to treat boils in the skin, but also as a fulminant infection as necrotizing fasciitis (or “flesh-eating disease”). About 1/3 of the cases of flesh-eating disease are caused by MRSA.

Clostridium difficile (C. difficile)

This gut bacterium is naturally resistant to many antibiotics. The rest of the gut bacteria usually suppress the growth of C. difficile. But many patients can get overgrowth of C. difficile in their gut following treatment with antibiotics. Recolonization with probiotics can help to reintroduce a balanced bowel flora. In the US about 500,000 individuals come down every year with diarrhea due to C. difficile. This leads to approximately 15,000 deaths yearly.

Vancomycin-resistant Enterococci (VRE)

Physicians find enterococci in the gut and the female genital tract of patients. They can become resistant when the patient is treated with vancomycin for another infection. The VRE can then become a problem of its own with difficult to treat infections in the genital tract of females, the gut or in wounds from surgery. It has become a problem in immunocompromised patients.

The gonorrhea causing bacteria

In the last 70 to 80 years Neisseria gonorrhoea, the cause of gonorrhea, has been treated with only one antibiotic, but gradually the bacterium developed antibiotic-resistance. Lately, with more and more resistant strains of Neisseria gonorrhoea, the CDC has recommended to treat gonorrhea with two overlapping antibiotics.

Carbapenem-resistant Enterobacteriaceae (CRE)

There are two problem bugs among this category of enterobacteria, Klebsiella species and Escherichia coli (E. coli). These bacteria reside in hospitals where they can accumulate and are present in patients with immune system compromise. Medical devices like catheters and ventilators transmit these bacteria. Once a patient is sick with CRE, there is a danger of blood poisoning (septicemia), which has a high death rate.

How do regular antibiotics kill bacteria and how can they become resistant?

Normally, when antibiotics are not resistant, they interfere with the cell membrane production of the bacteria. Specifically, conventional antibiotics prevent bacteria from synthesizing a molecule, called peptidoglycan. Without peptidoglycan bacteria are not stable enough to survive in humans. But there are other mechanisms as explained in this link how antibiotics manage to kill bacteria.

Now I like to address the question how bacteria can become resistant to conventional antibiotics. This happens with overuse of antibiotics, i.e. prescribing antibiotics when a person suffers from a viral illness where antibiotics do not work. Other overuse comes from agriculture where cattle in feed lots get antibiotics as growth promoters. The FDA is strongly criticizing this practice, because residuals of antibiotics in beef can alter the bowel flora in man. The antibiotics kill all the sensitive bacteria. But the resistant bacteria, that have undergone mutations and adapted to the antibiotics, will survive.

Why teixobactin and analogues can avoid resistance

Since the detection of teixobactin many analogues have been synthesized. A new antibiotic, teixobactin can overcome antibiotic-resistant superbugs. The teixobactin analogues need more fine tuning, but they will be a breakthrough in the treatment of resistant bacteria. As this peptide attacks two targets on bacteria, it is not easy for bacteria to develop resistance against these new antibiotics.

A New Antibiotic, Teixobactin Can Overcome Antibiotic-Resistant Superbugs

A New Antibiotic, Teixobactin Can Overcome Antibiotic-Resistant Superbugs

Conclusion

Resistant bacteria have become a serious health concern in the last decade. Physicians overprescribing antibiotics and farmers feeding antibiotics to cattle in feedlots as growth promoters were the driving forces. In 2015 came the breakthrough and discovery of teixobactin. This is a peptide with 11 amino acid units. Teixobactin is a derivative of a gram-negative bacterium, Eleftheria terrae. A new antibiotic, teixobactin can overcome antibiotic-resistant superbugs. In the meantime, researchers have been able to improve solubility by developing teixobactin analogues. More research is necessary. But all of the researchers who work in this field claim that this will very soon be extremely useful for patients with super bugs. This super-antibiotic will be a weapon fighting super bugs. Before the release of this medication clinical trials will be the next step.

Apr
18
2020

Changes of Metabolism by Inflammation

Dr. James LaValle gave a presentation about changes of metabolism by inflammation in Las Vegas. I listened to this lecture on Dec. 15, 2020. The 27th Annual World Congress on Anti-Aging Medicine in Las Vegas took place from Dec. 13 to 15th, 2019. His original title was: “Innovations in Metabolism and Metaflammation”. This talk was complex and as a result it may not be easy reading. But it shows how various factors can affect our metabolism and our life expectancy.

In the first place he understands “metabolism” as all of the chemical reactions together that make you feel the way you feel today. In the same way metabolism is the chemistry that drives you toward future health. It is equally important to note that disregulation of your metabolism occurs from global metabolic inflammatory signalling. As has been noted he called this “metaflammation” (inflammation affecting your metabolism).

Dr. LaValle said that understanding disruptors of your metabolism can lead to renew your health on a cellular level. The key to achieve this is to remove inflammatory signals.

Factors that accelerate aging and damage your metabolism

It is important to realize that several factors interfere with the normal aging process. Oxidative stress and inflammation are major factors. But hormone disbalance and increased blood sugar values and insulin resistance can also contribute to accelerated aging and damage your metabolism. Certainly, with a disturbance of the immune balance, autoimmune reactions can take place, which also does not help. In addition, pollutants from the environment derange the metabolism due to heavy metals that block important enzymatic reactions. In the minority there are also genetic factors that can interfere with a normal metabolism.

Many of the metabolic changes can lead to chronic inflammation. One source of inflammation can be lipopolysaccharides that stimulate the immune system to start an inflammatory process.

Many conditions are associated with inflammation such as diabetes, obesity, stress, the SAD diet (standard American diet), and liver or kidney damage.

How Metaflammation is developing

Metaflammation can start in the gut with microbiota alterations. The wrong types of bacteria can release lipopolysaccharides, and low grade endotoxemia develops. With obesity inflammatory kinins start circulating in the body. Stress can activate inflammatory substances in the brain and the rest of the body. Major contributors to inflammation in the body come from faulty diets. The Western diet contains too much sugar and refined carbs; it is too high in trans fats and saturated fats. It contains too many artificial additives, preservatives, salt, sweeteners and dyes. And it is too low in nutrients, complex carbs and fiber.

More problems with metaflammation

Kidney and liver illness can contribute to metaflammation. Several diseases come from chronic inflammation, like cardiovascular disease, type 2 diabetes, chronic kidney disease, depression, cancer, dementia, osteoporosis and anemia. Metaflammation alters the methylation patterns, which can slow down your metabolism. Increased blood lipids and chronic inflammation of the blood vessels lead to cardiovascular problems. The liver and kidneys are the major detoxification organs, and their disease leads to more metaflammation. Metaflammation also leads to hormone disbalances, sleep disorders and dysfunction of the immune system. The brain reacts to metaflammation with cognitive dysfunction and mood disorders. Muscle loss (sarcopenia) is another issue, so is osteoporosis. Finally, chronic metaflammation can cause cancer.

Major causes of metaflammation

The three major causes of metaflammation are changes of the gut microbiome, obesity and chronic stress. When the gut bacteria change because of a Western diet, the wrong bacteria release lipopolysaccharides that are absorbed into the blood. The gut barrier is breaking down and a low grade endotoxemia develops. With obesity adipokines, which are inflammatory substances secreted by the fatty tissue, circulate in the blood. Chronic stress activates inflammation in the brain and in the body.

Two major conditions are common with metaflammation: hyperlipidemia (high fat levels in the blood) and hyperglycemia. Both of these conditions change the metabolism and lead to cardiovascular disease (hyperlipidemia) or to type 2 diabetes (hyperglycemia). Both of these metabolic changes lead to one or more of the conditions mentioned above, accelerate the aging process and lead to premature deaths.

Interaction of various organ systems can cause metaflammation

Dr. LaValle stated that it is vital that your hormones stay balanced. With chronic stress cortisol production is high. This causes increased insulin production, reduced thyroid hormone and lowered serotonin and melatonin production in the brain. It also leads to autoimmune antibodies from the immune system and decreased DHEA production in the adrenal glands. In addition, growth hormone production and gonadotropin hormones are slowing down. We already heard that cortisol levels are up. The end result of these hormone changes is that the blood pressure is up and abdominal visceral obesity develops. The brain shows cognitive decline, with memory loss as a result. The bones show osteopenia, osteoporosis and fractures. The muscles shrink due to sarcopenia, frailty is very common. Heart attacks and strokes will develop after many years. The immune system is weak and infections may flare up rapidly. There are also higher death rates with flus.

Other mechanism for pathological changes with hormone disbalances

When Insulin is elevated, inflammatory markers are found in the bloodstream. This elevates the C-reactive protein and leads to damage of the lining of the blood vessels in the body. A combination of insulin resistance and enhanced atherosclerosis increases the danger for heart attacks or strokes significantly.

There is a triangle interaction between the thyroid, the pancreas and the adrenals. Normally the following occurs with normal function. The thyroid increases the metabolism, protein synthesis and the activity of the central nervous system. The pancreas through insulin converts glucose to glycogen in the liver. It also facilitates glucose uptake by body cells. The adrenal hormones are anti-inflammatory, regulate protein, carbohydrate and lipid metabolism and contribute to energy production.

Change of thyroid/pancreas/adrenals triangle when cortisol is elevated

When cortisol is elevated the balance of the thyroid/pancreas/adrenals’ triangle is severely disturbed. Cortisol is high, the T4 to T3 conversion is limited and, in the brain, there is hippocampus atrophy with memory loss and brain fog. The immune system will change with production of inflammatory kinins (IL-6 and TNF alpha). Insulin sensitivity is down, sugar craving up and weight gain develops (central obesity).

Change of thyroid/pancreas/adrenals triangle when the thyroid is depressed

The thyroid activity can be lower because of autoimmune antibodies (Hashimoto’s disease) or because of hypothyroidism developing in older age. This leads to decreased pregnenolone synthesis from cholesterol. As pregnenolone is the precursor for all the steroid hormones, the metabolism slows down profoundly. Mentally there is depressed cognition, memory and mood. The cardiovascular system shows reduced function. In the gut there is reduced gastric motility. The mitochondria, which are tiny energy packages in each cell, are reduced in number, which causes a loss of energy. There is increased oxidative stress, increased lactic acid production and decreased insulin sensitivity.

Cardiovascular disease not just a matter of high cholesterol

Dr. LaValle stressed that a heart attack or stroke is not just a matter of elevated cholesterol. Instead we are looking at a complicated interaction between hypothyroidism, diabetic constellation and inflammatory gut condition. The inflammatory leaky gut syndrome causes autoimmune macrophages and Hashimoto’s disease. The end result is hypothyroidism. The inflammatory kinins (TNF-alpha, IL-6) affect the lining of the blood vessels, which facilitates the development of strokes and heart attacks. You see from this that cardiovascular disease development is a multifactorial process.

Microbiome disruption from drugs

Drugs affecting the intestinal flora are antibiotics, corticosteroids, opioids, antipsychotics, statins, acid suppressing drugs like protein pump inhibitors (PPI’s) and H2-blockers. Other factors are: high sugar intake, pesticides in food, bactericidal chemicals in drinking water, metformin, heavy metals and alcohol overconsumption. Chronic stomach infection with H. pylori, stress and allergies can also interfere with the gut microbiome.

The microbiome disruption affects all facets of metabolism. This means that there can be inhibition of nutrient absorption and this may affect the gut/immune/brain axis. There are negative effects on blood glucose levels and insulin resistance. A disturbance of the sleep pattern may be present. A significant effect on the hormonal balance can occur (thyroid hormones, sex hormones and appetite related hormones). When liver and kidney functions slow down, there is interference of body detoxification.

Dr. LaValle talked more about details regarding the gut-brain-immune pathology. I will not comment on this any further.

Changes of Metabolism by Inflammation

Changes of Metabolism by Inflammation

Conclusion

Dr. LaValle gave an overview in a lecture regarding changes of metabolism by inflammation. This took place at the 27th Annual World Congress on Anti-Aging Medicine in Las Vegas from Dec. 13 to 15th, 2019.

This article is complex and contains a lot of detail, but there is one simple truth: oxidative stress and inflammation are major factors that influence our health on many parameters and lead to a list of illnesses. They lead to hormone disbalance and increased blood sugars and insulin resistance, which can also contribute to accelerated aging and damage of your metabolism. Dr. LaValle explained how high cortisol from chronic stress can lead to low thyroid hormones and in the brain, there is hippocampus atrophy with memory loss and brain fog. With alterations of the immune system there is production of inflammatory kinins (IL-6 and TNF alpha). Insulin sensitivity is down, sugar craving up and weight gain develops (central obesity). It does not stop there! We put our hope in medications, but the sad truth is that there are

Drugs that change the gut biome

Many drugs that are common also change the gut biome with resulting increased permeability of the gut wall (leaky gut syndrome). This overstimulates the immune system and leads to autoimmune diseases like Crohn’s disease and rheumatoid arthritis. Whenever there is an injury to the gut barrier, the blood brain barrier is following suit. This is how brain disease can develop as a result of a change in the gut biome. Impaired cognition, memory and mood can result from this. Alzheimer’s disease is one of the worst conditions that may be related to a combination of gut inflammation, chronic stress and inflammatory kinins.

Mar
07
2020

Eat Right for a Long Life

Dr. Felice Gersh gave a talk at a conference in Las Vegas stressing the importance to eat right for a long life. This was at the 27th Annual World Congress on Anti-Aging Medicine in Las Vegas from Dec. 13 to 15th, 2019. The actual title of her presentation was “Nutrition for Longevity”.
Dr. Gersh has a fellowship in Integrative Medicine at the University of Arizona School of Medicine.

In the first place she pointed out that an anti-inflammatory diet consists of vegetables, fruits, nuts, whole grains, healthy oils like olive oil and fish. This is a modified Mediterranean diet. On the other hand, with a pro-inflammatory diet or Western diet, you eat high fat, cholesterol, lots of protein from red beef, high sugar, excessive salt and a lot of processed and fast-food.

Prevention of diseases

It is important to realize that for prevention of cardiovascular disease, cancer and degenerative diseases you need to eat fruits and vegetables, which contain important phytochemicals. They contain a wide variety of molecules, like carotenoids, vitamins and polyphenols. Another key point is that cruciferous vegetables (broccoli, Brussels sprouts, and kale) contain glucosinolates, which are sulfur-containing compounds. They protect you from cancer.

Vitamins and magnesium

It must be remembered that in order to strengthen the immune system and prevent hardening of the arteries (atherosclerosis) we need the following: omega-3 and omega-6 fatty acids, the enzyme Co-Q10, vitamin A, B complex, C, D, E, carotenoids, phytosterols, stilbenes and flavonoids. Another key point is that magnesium is extremely important. Many of our dietary habits have reduced magnesium intake to a minimum. Our soils are depleted of magnesium, it is no longer in drinking water, and it is absent in processed foods. However, magnesium is involved as a co-factor in more than 700 enzymatic reactions in our bodies. Magnesium is involved in heart contractions, is important to maintain our blood pressure and is important for glycemic control. It is also important for bone development and for DNA and RNA synthesis. Magnesium binds serotonin and dopamine to their receptors and plays a role in many more body functions.

Brassica vegetables

This group of vegetables consists of broccoli, cauliflower, green cabbage and Brussels sprouts. Notably, they have long been recognized to lower the risk of many cancers. The first thing to remember is that the active ingredients in them are glucosinolates and isothiocyanates. Certainly, food preparation has a lot of influence on maintaining beneficial substances in the brassica vegetables. To emphasize, finely shredded vegetables had a marked decline of their glucosinolate levels by 75% within only 6 hours. On the negative side, microwave cooking destroys 74% of glucosinolates, but on the positive side, storage in room air preserves almost all of the glucosinolates for 1 week. In addition, stir frying brassica also preserves the glucosinolates. This reference points out how fruit and vegetables can contribute to cancer prevention.

The gut microbiome

The Western diet leads to a change in the gut flora with Gram-negative bacteria taking over the healthy gut flora and disrupting the intestinal barrier. To emphasize, this result is called endotoxemia. Part of this is increased serum endotoxin, which mainly consists of lipopolysaccharides. Indeed, it causes gut inflammation and a breakdown of the gut barrier. When this happens, autoimmune antibodies are produced. To put it another way, the Western diet undermines your health. In a word, high fat foods and added sugars (refined carbohydrates) lead to increased Gram-negative bacteria and the disruption of the intestinal barrier.

An unhealthy diet causes disease

In the long run this causes autoimmune diseases, leads to higher heart attack rates and to diabetes. Healthy gut bacteria in fact help to digest fibre, which leads to three short-chain fatty acids: butyrate, acetate and propionate. For the most part, they are important as energy source, affect cardiometabolic health and appetite. On balance, butyrate also helps to maintain the blood brain barrier.

Importance of fiber

Higher fiber content in food leads to less cardiovascular disease, has positive effects on obesity and the metabolic syndrome. Fiber changes the microbiome in the gut, leads to less gut permeability and more short-chain fatty acids production.

The best diet

  • 60% to 70% complex carbohydrates are the foundation of a healthy diet. It consists of vegetables, green leafy and root vegetables, beans, legumes, whole grains and fruit.
  • Eat healthy fats from nuts, olives, seeds, krill or fish oil. Limit fat intake to 18 to 28% of your daily calorie intake. Avoid hydrogenated fats. Limit your saturated fatty acid intake. 85% chocolate is OK. Otherwise consume olive oil and omega-3 fatty acid containing foods (from seafood and fish).
  • Add about 12% of the daily calorie consumption as protein per day. Choose fish, seafood, lean cuts of chicken, only the occasional red meat (organic or grass-fed meat)
  • Eat lots of fiber, eat organic and minimally processed food. Limit sugar, fat and salt. Avoid antibiotics from the agricultural industry, sweeteners, gluten and excessive alcohol intake. Take a daily probiotic and eat probiotic food. Eat three meals a day, a big breakfast, a moderately-sized lunch and a small dinner. A fasting mimicking diet once per month for 5 days activates your longevity genes.
Eat Right for a Long Life

Eat Right for a Long Life

Conclusion

Dr. Felice Gersh gave a talk at a conference in Las Vegas. This was at the 27th Annual World Congress on Anti-Aging Medicine in Las Vegas from Dec. 13 to 15th, 2019. She said that we need to eat right for a long life. She gave a thorough outline of what to eat and what not to eat. It is important to note that she suggested to cut out additional refined sugar and processed food. The bacteria in the gut must be normal, or the gut barrier breaks down. This failure can cause autoimmune diseases. Eating lots of vegetables and fruit as well as fiber will help to keep your gut bacteria normal.

What foods to eat

A Mediterranean type diet gives you the right foods that you need for your health. Avoid the Standard American diet as it is unhealthy and kills the good gut bacteria. Brassica vegetables like broccoli, cauliflower, green cabbage and Brussels sprouts prevent the development of many cancers. Eat three meals a day, a big breakfast, a moderately-sized lunch and a small dinner. This fits best into the diurnal rhythm of your gut bacteria. Eat right for a long life!

 

Jan
18
2020

Antibiotics In Children Can Trigger Allergies And Asthma Later In Life

Whoever treats a child’s cold must know that antibiotics in children can trigger allergies and asthma later in life. This is what a study released on Dec. 20, 2019 has shown. The researchers examined records of 798,426 children seen at the Department of Defense TRICARE health care program. They were born between 2001 and 2013. The physicians examined the children later again for allergies. The more antibiotics the children received in childhood, the more severe the youngster’s allergies were later in life.

More details about the study

The researchers found that different antibiotic types had different risks to cause allergic reactions later in life.

  • Penicillin: 1.3-fold risk
  • Penicillin with a β-lactamase inhibitor: 1.21-fold risk
  • Macrolides: 1.28-fold risk)
  • Cephalosporins: 1.19-fold risk
  • Sulfonamides: 1.06-fold risk

The type of allergies that the children developed later in life were food allergies, anaphylaxis, asthma, atopic dermatitis, allergic rhinitis, allergic conjunctivitis or contact dermatitis. The researchers stressed that their finding indicated an association between taking antibiotics and developing allergies later. It was not a causal relationship.

Food allergies in more detail

Anaphylaxis

This allergic condition is an emergency and requires immediate medical attention. It can occur when the body overreacts to peanuts or penicillin. It can occur with foods, and the reaction is sudden and severe. The symptoms may include wheezing, shortness of breath, a cough or tightness in the throat. The blood pressure may drop leading to light-headedness and passing out. The skin may show hives, swelling and a rash. The digestive symptoms may be nausea, vomiting and diarrhea. Other symptoms may involve itching eyes, headaches, anxiety and a feeling of impending doom.

Asthma

Airborne grass and tree pollens, mold spores and dust, but also peanuts and other strong allergens can trigger an asthma attack. The symptoms can be shortness of breath, wheezing, tightness in the chest, trouble falling asleep because of coughing and being short of breath.

Atopic dermatitis (eczema)

Often atopic dermatitis starts below the age of 5 and can last until late adolescence or adulthood. The symptoms can be dry skin, itching red patches of skin and thickened scaly skin. Allergic contact dermatitis is common in patients with atopic dermatitis.

Allergic rhinitis

People who suffer from allergic rhinitis are sensitized to particles in the air like grass and tree pollen, molds or cigarette fumes. They develop a stuffy nose, itching and watery eyes, sneezing and swelling around the eye lids. An allergist can do skin scratch tests to find out what the patient is allergic to. Subsequently, if the allergies are strong, the allergist may decide to start desensitization with allergy shots.

Allergic conjunctivitis

A person who is allergic to pollen and mold spores will react to this when in contact with it and often develop allergic conjunctivitis. An eye inflammation will develop within a few minutes leading to swelling of the conjunctiva around the eye ball. The eyes end up looking red, itching, burning and being watery.

Contact dermatitis

Contact dermatitis develops when your body brushes against a substance that your body has been previously sensitized to. One example is poison ivy contact dermatitis. But many other substances can cause similar reactions: solvents, shampoos, permanent wave solutions and rubbing alcohol. In addition, plants, bleach and detergents, fertilizers, pesticides and airborne substances (sawdust, dust from woollen materials) can also do the same.

The gut biome

Dr. Purvi Parikh is an allergist and immunologist at NYU Langone Health in New York. She was not involved in the study, but commented to it as follows: “One reason why there might be an association is because our microbiome, specifically in our gut, plays a large role in our immune systems. Antibiotics are known to not only kill the bacteria that are causing an infection, but also ‘good’ bacteria our immune system needs to protect us from developing allergic or autoimmune diseases.”

Treat bacterial infections with antibiotics when needed

She went on to say: “Overall, parents should know that this study shows an association but not necessarily cause and effect. So, if a child truly needs an antibiotic for a bacterial infection, they should not withhold it due to fear of allergic disease. However, on that same note, one should not over use antibiotics if not needed – for a virus or a cold – as there may be long-term consequences from over use.”

Antibiotics In Children Can Trigger Allergies And Asthma Later In Life

Antibiotics In Children Can Trigger Allergies And Asthma Later In Life

Conclusion

A new study showed that antibiotics can cause allergies and asthma later in life. The reason seems to be that our gut bacteria react to the antibiotics and the gut dysbiosis (disbalance of the gut bacteria) persists, when the antibiotics have been discontinued. The immune system can then react in ways that are detrimental to the child and adolescent. Anaphylaxis, asthma, atopic dermatitis, allergic rhinitis, allergic conjunctivitis or contact dermatitis are all different manifestations of allergies that can develop later in life. At this point we only know that there is an association between these allergic manifestations and the antibiotic use in childhood. More clinical trials will need to shed a light on what causes allergies in some children, but not in others.