Comments on Probiotic Research
From Universiti Putra Malaysia (UPM) August 2014 – C. difficile is an opportunistic pathogen found in the intestines of approximately 3% of healthy adults and 40% of infants. The bacterium causes a spectrum of diseases in humans, ranging from mild to severe. Infection rates are particularly high in North America and European countries. Studies have shown that this bacterium is responsible for 10-25% of antibiotic-associated diarrhoea cases, 50-75% of antibiotic-associated colitis cases, and 90-100% of antibiotic-associated pseudomembranous colitis, respectively.
Probiotics have shown promise for treating patients with recurrent Clostridium difficile infections
Probiotics are effective in preventing hepatic encephalopathy in patients with cirrhosis of the liver, according to a new study in Clinical Gastroenterology and Hepatology.1
In mid-1980s, I introduced the term LAPs (lactic acid-producing) as an abbreviation for health-promoting bowel microbes that produce lactic acid and other immune-strengthening substances. I chose the term TAPS (toxin-producing) for the gut microbes that injured all body organs under varying conditions.
LAPs build strong defenses in many ways. TAPs are equally versatile in their production of a very large number of toxins, including:
- mycotoxins (mold toxins);
- oxygen-depriving (vaso-constrictive) amines such as histamine, tyramine, agmatine and cadaverine;
- ammonia and related compounds;
- phenols and related phenolics;
- tryptophan metabolites and other toxic amino acids;
- certain harmful steroids; and
- some carcinogenic substances.
Regrettably, this area has received limited research funding. Undoubtedly, future research will uncover a host of as yet undetected bacterial and fungal toxins and metabolic villains.
LAPs/TAPs dynamics are profoundly influenced by food choices. American and British individuals show overgrowth of some TAPs, including bacteroides, firmicutes, clostridia, and others. Japanese and many indigenous populations produced much smaller quantities of such toxins. It is now well established that these differences are due to chemicalized foods and abundance of fats and animal flesh foods in the former.
Microbes Are Master Chemists
Microbes execute an enormous number of biochemical reactions. Farmers employ them to turn compost into fertilizer long before microbiologists learned about healthful and noxious aspects of their metabolism, including:
- inactivation of digestive enzymes (trypsin and chymotrypsin)
- destruction of enzymes located on the surface of cells lining the gut
- deconjugation of hormones such as estrogen and bile acids
- denaturation of bile steroids
- breakdown of food flavonoids
- hydrogenation of polyunsaturated fatty acids in food
- conversion of some compounds into carcinogens.
List of Major LAPs and TAPs
Below is a list below the three genera of LAPs and several genera of TAPs that most frequently populate the bowel ecosystem.
Proteus, Pseudomonas, Salmonella, Escherichia
Bacteroides, Clostridium, Peptococci, Peptostreptococcus
About 30 species of LAP microbes have been identified. Some important members of these three groups (L, Lactobacillus; B, Bifidobacterium; S, Streptococcus) include the following:
L. acidophilus B. bifidum
L. bulgaricus B. adolescentis
L. lactis B. infantis
L. casei B. breve
L. helveticus B. longus
S. faecium S. thermophilous
Food production technology threaten LAP microbes and promotes the growth of TAPs. . In addition, alcohol, nicotine, various pharmacologic agents, and highly processed and “preserved” foods have a negative impact on lactic-acid producers.
Normal fecal flora in man includes the following: Bacteroidaceae (Bacteroides and Fusobacteria), Eubacteria, Lactobacilli, Bifidobacteria, Veillonellae, Acidaminococci, Megasphaerae, Peptococcaceae (Ruminococci, Peptococci and Peptostreptococci), Clostridia (C. perfrigens and other species), Enterobacteriaceae, aerobic Lactobacilli, Streptococci, Staphylococci, and yeast and fungi (often used interchangeably)
Some LAP microbes suppress tumor cells in rats. This factor is not of direct relevance to human canaries — at least not yet, though in time accelerated oxidative damage is likely to increase the incidence of cancer in chronic fatigue states.
What is bowel ecotoxicity? How may it be detected? The answers to those questions can be both simple and complex. As for the former, ecotoxicity exists when endogenous and exogenous toxins in the bowel exceed its ability to ability to rid itself of those molecular species. Ecotoxicity exists when the characteristics of health described in an earlier chapter are not present, month after month, year after year. As for the latter, below I provide an incomplete answer. (Complete answer to those questions may indeed not be forthcoming for decades.)
Until the dawn of the pesticide and xenobiotics age, the human bowel flora was, in a broad sense, in equilibrium with that of the soil. As I child I recall pulling carrots from my ‘personal’ vegetable patch, barely washing them, and eating them with relish. I also recall the crunch of some sand between my then-strong teeth. That era, of course, is long gone. The soil all over the globe has been now diffusely and unrelentingly chemicalized. Today if a child were to eat vegetables smeared with dirt, she will not be exposed to the soil flora that I was then. Children today can be expected to take variable doses of pesticides, herbicides, and xenobiotics with their vegetables and fruits.
After the reunification of Germany, pediatricians from ‘clean’ Munich in West Germany and ‘polluted’ Leipzig from East Germany conducted a collaborative study to determine how much higher the incidence of asthma in the East German town was notorious for its industrial air pollution. I would have predicted they would see more asthma in children raised on the clean but highly chemicalized soil of Munich than in Leipzig, with its polluted air but far less chemicalized soil. That, indeed, was the case when the results of that study were published.
Not unexpectedly, LAPs-TAPs dynamics are profoundly influenced not only by the soil composition but also by food choices. American and British individuals show overgrowth of some TAPs, such as bacteroides and some types of clostridia, with much higher frequency than is seen in Japanese, Indians and Ugandans. It appears likely that these differences are due to excess use of antibiotics and an abundance of fats in the former populations’ diet.
A very revealing look into the presence and degree of bowel ecotoxicity is provided by data concerning 24-hour urinary excretion of mycotoxins, bacterial toxins, and related molecular species produced largely in the bowel. The table below shows data for 100 patients with chronic energy deficit disorders.
Frequency of Increased Urinary Excretion of Compounds Indicative of Bowel Ecotoxicity in 100 Patients With Dysoxygenosis
Absence of the Guardian Angels in Chronic Disease and Disorders Patients
Perhaps the best way to gain some sense of the dynamics of bowel ecotoxicity is to examine how healthful bowel flora in bygone years helped preserve health. Consider how the LAP angels promote healthful aging:
First and foremost, LAPs keep TAPs under check. It appears that this essential role is played through different mechanisms that include simple physical crowding out of the potential pathogens as well as production of antimicrobial substances. L. acidophilus produces acidophilin, acidolin and bacterlocin; L. plantartum produces lactolin; L. bulgaricus produces bulgarican; and L. brevis secretes lactobacillin.
Second, LAPs produce many lifespan molecules. Notable among them are members of the vitamin B complex, especially folic acid and biotin, and vitamin K. Lactobacillic acid is an important fatty acid that is produced by some lactic-acid producers and is then converted into essential fatty acids. Another notable molecule in this context is tryptophan—this is likely to be one of the mechanisms by which yogurt has been reported to be beneficial in cases of fibromyalgia, chronic fatigue, and related conditions.
Third, LAPs play a pivotal role in digestion. Lactose intolerance is a very common clinical problem. It is often not fully appreciated that a major portion of lactose ingested in dairy products is actually broken down to simpler sugars by lactase enzymes produced by lactic acid producers. Lactic acid and lactase producers also play important roles in protein digestion. This is one of the primary reasons protein intolerance is so common among individuals with altered states of bowel ecology.
Fourth, LAPs actively break down some toxins produced during metabolism such as ammonia, free phenols and polypeptides.
Fifth, LAPs normalize bowel transit time and are effective in controlling infant and adult diarrhea.
Sixth, the antiviral and antifungal roles played by LAPs, having long been empirically suspected by nutritionists and holistic physicians, have recently been documented with research studies.
Seventh, the cholesterol-lowering effects of fermented milk have been attributed, among other mechanisms, to orotic acid, which facilitates fat metabolism in the liver.
Eighth, some LAP microbes suppress tumor cells in rats. This factor is not of direct relevance to human canaries — at least not yet, though in time oxidosis and dysoxygenosis is likely to increase the threat of cancer in persons with OD (oxidative-dysoxygenative) states.
It is noteworthy that all eight elements mentioned above increase, directly or indirectly, the fury of oxidosis, acidosis, and dyxoxygenosis.
RESTORATION OF BOWEL ECOLOGY
Disruptions of bowel ecology can be arrested and reversed only with a gardener’s sense of tending to the soil, nurturing the plants, and respect for the sunshine. That, of course, is the theme of this chapter. The sun-related factors — chronic anger, hostility, conflict, and a sense of being a victim — both slow down the bowel transit time and significantly reduce perfusion in different parts of the alimentary tract. Those anatomically-mediated responses, of course, form the core of the so-called stress response. I discuss this subject at length in What Do Lions Know About Stress and Healing Miracles and the Bite of the Gray Dog .
The Seed-Feed-and-Occasionally-Weed Approach to Restoration of Bowel Ecology
In 1994, in The Canary and Chronic Fatigue, I described my seed-feed-and-occasionally-feed approach to addressing the chronic ecologic issues of the alimentary tract. Below, I reproduce some text from that volume:
Seeding is the repopulation of the gut with microflora that have been destroyed by indiscriminate use of antibiotics or crowded out by the unrestrained proliferation of yeast and bacterial organisms such as the Proteus and Pseudomonas species.
The “guardian angel bacteria” for bowel ecology belong to the Bifidobacterium and Lactobacillus species. Some other species also play protective roles. In health, these organisms provide the necessary counterbalance to the growth of yeast and pathogenic bacterial organisms. Beyond this, these organisms produce several molecules that play critical roles in our molecular defense systems.
Feeding is the use of some growth factors that the normal bowel flora require to flourish. These include biotin, pantetheine, Vitamin B12 and others. We clinicians have used Vitamin B12 for decades with good clinical results (to the great chagrin of those “academicians” who considered it quackery because they couldn’t understand how this vitamin could ever help anybody except those with pernicious anemia). One of the principal mechanisms by which vitamin B12 exerts its myriad beneficial effects is by serving as a “growth hormone” for health-preserving bowel flora. Of course, this vitamin has several other essential roles. It plays a role in the citric acid cycle (the main molecular pathway for energy generation where it facilitates the conversion of methylmalonyl-CoA to succinyl-CoA) and is essential for cell maturation. Further, Vitamin B12 benefits many patients with neuropsychiatric disorders unassociated with anemia or macrocytosis.
Occasional weeding is the use of several natural substances that are known to suppress the overgrowth of pathogenic bacteria, viruses and yeasts. During initial treatment, I frequently use oral nystatin or fluoconazole (Diflucan) for short periods of two to three weeks, partly for diagnostic and partly for therapeutic reasons (how a person with one of the ABE states responds to these agents is useful in assessing the degree of damage to bowel ecology). Extensive clinical experience has convinced me that long-term clinical results are far superior when the use of drugs is kept to a minimum.
Simple-minded efforts to “get rid of the yeast” with nystatin and “yeast-free diets” usually yield poor long-term results. Cold hands are associated with “cold bowel.” Cold hands and cold bowel are the result of oxidatively-damaged thyroid enzymes (underactive thyroid gland), oxidatively-damaged autonomic nerve cells and fibers (dysautonomia) or an oxidatively-overdriven adrenalin gland (the relentless chatter of the cortical monkey). None of these problems can be effectively managed with yeast-free diets and Nystatin. Of course, there are other essential issues of nutrition, environment, food and mold allergy, and fitness. In the management of battered bowel ecosystems, it is essential to consider the biologic individuality of the patient. It is necessary to adopt an integrated, long-term approach that addresses all relevant issues of bowel flora and parasites, bowel transit time, bowel ischemic patterns, IgE-mediated disorders related to candida and other yeast antigens, malabsorptive dysfunctions, and secondary systemic consequences.
Physicians who are not familiar with natural therapies for managing chronic bowel and gastric disorders are in for a pleasant surprise. A very large number of effective natural agents are available to them. Extensive clinical experience has convinced me that for nonlife-threatening, chronic disorders, natural therapies are far superior to the huge array of drugs that are foisted upon us.
Following are important consideration in integrative management of chronic gastric and bowel disorders:
First, all patients should be offered standard drug therapies for acute disorders when any question exists about impending clinical crises or risk of serious complications.
Second, all patients managed with natural agents should be prepared for slow and sustained recovery over weeks and months. It is my practice not to wean my patients off drugs prescribed by other physicians. Rather, my clinical strategy is to go for gentle restoration of bowel and gastric ecologies. The patients sense clinical improvement within several days or some weeks. It is at this time that they ask me if they should begin to reduce the dose of drugs they are taking, and I am only too happy to provide guidance on how to do so gradually.
Third, all patients are required to attend a full-day workshop in which I give detailed information about the devastating impact of internal and external environments on our biology. In addition, nutrition and exercise classes are given by the nursing staff at the institute.
Fourth, all patients must be managed with an overarching philosophy of holistic molecular relatedness in human biology. I repeat this essential point several times at the risk of offending the reader because it is the very essence of the new medicine that the problems of the 21st century call for.
Fifth, and this is of critical importance for the general reader, a self-help approach to health requires guidance from a knowledgeable professional. Safety first. This is the first principle of molecular medicine as it must be for all other types of medicine.