MICROBIAL NUMBERS AND THE INTESTINAL ECOSYSTEM

The 25-35 foot long GI tract of an adult human is estimated to harbor about 100 trillion viable bacteria. This is approximately 10 times the total number of cells in the human body. These live bacteria account for around 2 lbs of a body's weight and are known as intestinal or gut flora. Viruses, fungi and protozoa can also be present, but these normally form only a minor component of the total resident population of microorganisms in healthy individuals.

The density of microorganisms in the gut flora increases dramatically from 10-1,000 CFU/ml in the stomach to 10-100 billion CFU/gm in the large intestine⁽¹⁾ and these belong to as many as 400 different species, and anaerobic bacteria outnumber aerobic bacteria by a factor of 1000:1. Anaerobic flora is dominated by Bacteroides spp., bifidobacteria, propionibacteria and clostridia. Among aerobic and anaerobic bacteria enterobacteria, mainly E.coli, and enterococci predominate. As indicated in table 1, Bifidobacteria account for approximately 90% of the total colonic beneficial microflora. Populations of Lactobacilli are several orders of magnitude smaller than Bifidobacteria.


Bacteria have been estimated to constitute 35-50% of the volume of the contents in the human colon. They profoundly influence nutritional, physiologic and protective processes. Both direct and indirect defensive functions are provided by the normal microbiota. Specifically, gut bacteria directly prevent colonization by pathogenic organisms by competing for essential nutrients or for epithelial attachment sites. By producing antimicrobial compounds, volatile fatty acids, and chemically modified bile acids, indigenous gut bacteria also create a local environment that is generally unfavorable for the growth of enteric pathogens⁽¹²⁾. This phenomenon is called Colonization Resistance, which can be defined as the ability of microorganisms belonging to the normal gut microflora to impede the implantation of pathogens. This function of the microflora is also known as the barrier effect. While probiotic bacteria improve colonization resistance, consensus thinking is that the importance of lactic acid bacteria as probiotic agents lies more in the indirect mechanisms such as immunomodulation.

The normal or indigenous microflora of man consists of a resident (autochtonous) part, which largely stays with the host organism, and a transient part, which may dynamically change in composition. This is not unique for man as it also applies to animals. The turnover of the transient part of the microflora of the digestive tract depends both on the composition of the resident flora or Colonization Resitance, and on the degree of contamination (qualitatively and quantitatively as well) of ingested food and beverages. Regarding the latter, hygienic conditions of the environment is important.

The defense systems in the gut can be split into three parts: the gut flora, the gut mucosa and epithelium and the related immune system, as illustrated in Fig. 1.


Figure I: Illustration of the natural defense systems of the intestine (Source: DanoneVitapoie)
The intestine, composed of villi and crypts, is coated with mucus that protects the intestinal cells. At the bottom of the crypts lie specialised cells known as Paneth cells that are able to release antimicrobial molecules into the gut lumen.The intestinal flora, present mainly in the colon, forms a natural barrier to pathogens.The intestinal immune system comprises cells disseminated beneath the epithelium and also between epithelial cells (intraepithelial lymphocytes). Lymphocytes are also found within more organised structures, lymphoid follicles, with a central region of B lymphocytes and a lateral region ofT lymphocytes. Above these structures, we find M cells, which are specialised in transporting particles to the follicle.These areas of the intestine are known as Peyer's patches.When a lymphocyte is activated by a dendritic cell presenting an antigen, it leaves the mucosa in lymph and enters the bloodstream via the thoracic canal. This activated lymphocyte then colonises either the same mucosa or other mucosal effector sites.

Although less complex than the gastrointestinal microflora, the normal vaginal microflora of a premenopausal woman is composed of a variety of bacterial species. Anaerobes are most frequently isolated and appear in numbers of 10⁷ - 10⁹ CFU/ml of vaginal secretion. Lactobacillus spp. is the most frequently isolated genus found in the highest numbers. They play a role in maintaining the balance of the normal vaginal flora by producing hydrogen peroxide. It has been shown that approximately 70% of premenopausal, healthy women harbor hydrogen peroxide-producing lactobacilli. Corynebacterium, Staphylococcus and Bacteroides spp. are among the anaerobes frequently isolated.

INTESTINAL MICROFLORA IN THE NEWBORN INFANT

Fetuses are sterile in the womb, but beginning with the birth process, infants are exposed to microbes that originate from the mother and the surrounding environment including breast milk or formula⁽¹²⁾. The infant tends to acquire the flora swallowed from the vaginal fluid at the time of delivery. Because vaginal flora and intestinal flora are similar, an infant's flora may closely mimic the intestinal flora of the mother⁽¹⁵⁾.

Another factor affecting the intestinal flora of the newborn is delivery mode. A normal vaginal delivery commonly permits transfer of bacteria from the mother to the infant. During cesarean deliveries, this transfer is completely absent. These infants commonly acquire and are colonized with flora from the hospital's environment and, therefore, their flora may differ from maternal flora. Infants delivered by cesarean section are colonized with more anaerobic bacteria, especially Bacteroides, than vaginally delivered infants. Clostridium perfringens is the anaerobic bacterium most frequently isolated after cesarean deliveries. When colonized, cesarean delivered infants less frequently harbor E. coli, and more often klebsiella and enterobacteria⁽⁷⁾.

The initial colonizing bacteria vary with the food source of the infant. In breast-fed infants, Bifidobacteria account for more than 90% of the total intestinal bacteria. The low concentration of protein in human milk, the presence of specific anti-infective proteins such as immunoglobulin A, lactoferrin, lysozyme, and oligosacharides (prebiotics), as well as production of lactic acid, cause an acid milieu and are the main reasons for its bifidogenic charachtersitics. In bottle-fed infants, Bifidobacteria are not predominant⁽¹³⁾. Instead enterobacteria and gram-negative organisms dominate because of a more alkaline milieu and the absence of the prebiotic modulatory factors present in breast milk.

The establishment of an intestinal microbial ecology is very variable at the beginning but will become a more stable system similar to the adult microflora by the end of the breastfeeding period.

Other factors affecting the intestinal microflora of the infant include geographical differences (industrialized vs. developing countries) and administration of antibiotics in neonatal intensive care.

HOW DO PROBIOTICS WORK?

Probiotics must be ingested regularly for any health promoting properties to persist. It is possible to manipulate the composition of the intestinal microflora in adults through dietary supplementation with probiotics. This concept is gaining popularity throughout the world.

The mode of action of a probiotic may include host microflora modulation, e.g., by improvement of the microbial balance via interaction of orally applied viable microbes with the microflora in the digestive tract lumen, the modulation of host metabolic activities, e.g., by stabilizing digestive enzyme pattern, and immunomodulation, e.g., by activation and regulation of mucosa-associated and systemic immune system responses. These modes of action are also strain-dependent.

The intestinal microflora provides protection against a broad range of pathogens, including certain forms of Clostridia, Escherichia Coli, Salmonella, Shigella and Pseudomonas, as well as yeasts such as Candida albicans.

MECHANISMS OF ACTION OF PROBIOTICS

Effect of Probiotics on the Intestinal Epithelium.
         A. Promote tight contact between epithelial cells forming a functional barrier.
         B. Reducing the secretory and inflammatory consequences of bacterial infection.
         C. Enhancing the production of defensive molecules such as mucins.
 
Immune Effects of Probiotics
         A. Probiotics as vehicles to deliver anti-inflammatory molecules to the Intestine.
         B. Enhance signaling in host cells to reduce inflammatory response.
         C. Switch in immune response to reduce allergy.
         D. Reduce the production of inflammatory substances.

EFFECTS OF PROBIOTICS ON THE INTESTINAL MICROFLORA

Probiotics modulate the composition of the intestinal microflora. The survival of ingested probiotics in different parts of the gastrointestinal tract differs between strains. As a result of their concentration in the lumen, they contribute to transient modulation of the microflora ecology, at least during the period of intake. This specific change may be seen for a few days after the start of consumption of the probiotic preparation, depending on the capacity and dosage of the strain in question to modulate the functioning of the gastrointestinal tract. Results show that with regular consumption, the bacteria temporarily colonise the lower intestine. Once consumption stops, the number of probiotic microorganisms quickly falls (see Figure 2 below). This applies to all probiotic supplements available in the market today
.

Figure 2

Many studies have demonstrated significant shifts in bacterial counts in human faeces following consumption of specific probiotic strains, generally resulting in increased numbers of health-promoting genera (Lactobacillus and Bifidobacterium) and decreased numbers of potentially harmful ones (such as several strains of Clostridum, Enterococcus and Candida). These studies, however, reflect the bacteriological situation in faecal matter only and do not provide an accurate picture of the situation in different parts of the gastrointestinal tract or in the mucosal layer of the gut. Furthermore, many species of intestinal bacteria from faecal samples cannot be cultured on specific plates.

Probiotic bacteria modulate the metabolic activity of the gut flora. Probiotics, being able to lower the pH in the intestinal tract, may thus be able to interfere with the enzymatic activity of the flora.

CP-1: A HIGHLY EFFECTIVE PROBIOTIC SUPPLEMENT

Qualities of an effective probiotic dietary supplement include the following⁽⁴⁾:

     1) Must be of human origin
     2) Exert a beneficial effect on the host
     3) Be nonpathogenic and nontoxic
     4) Contain a large number of viable cells
     5) Be capable of surviving and metabolizing in the gut
     6) Remain viable during storage and use
     7) Be antagonistic to pathogens.

Our custom probiotic formulations meet all these requirements.

Our five-strain Adult Formula CP-1 capsules have a total bacterial count of 50 billion microorganisms per capsule at date of expiration. This is verified by certified laboratory analysis. Upon request, we will be pleased to share with you the most recent independent laboratory test results, that indicated 73 billion per capsule.

Adult Formula CP-1's high bacterial count, broad-spectrum formulation and high viability of friendly bacteria all contribute to its effectiveness. It is dairy free, hypoallergenic, and does not contain any artificial colors, flavors, preservatives, sugar, gluten or FOS. Our custom probiotic powder formulations range from 100 to 400 billion microorganisms per gram, the highest potency of any probiotic formulation available in the market today.

We do not use prebiotics, such as fructooligosacharides (F0S) or inulin, in our formulations, with a view to eliminating possible adverse reactions by highly allergic and sensitive individuals, such as Candida or irritable bowel disease (IBD) patients. Most FOS in today’s market contain 5-40% free sugar. We suggest getting FOS from vegetables such as onion, garlic, asparagus, dandelion, artichokes and leeks, which have many additional health promoting and nutritional benefits..

DOSAGE

Growth characteristics of probiotics appear to be species-specific and depend on the amount ingested and duration administered. The greater the bacterial imbalance in the digestive system, the higher the dosage required for positive and measurable results.

Dosage differs from individual to individual. You must find the appropriate dosage for you, which may be 1, 2 or 6 of our Adult Formula CP-1 capsules per day. We suggest gradually increasing probiotic dosage from one capsule (50 billion cfu’s) to a maximum of six capsules per day to find the appropriate dosage. Like a fingerprint, the composition of the intestinal microflora is quite different from one human to another, which is an immediate obstacle in manipulating it. Hence the appropriate dosage of probiotics needs to be determined individually.

How you use a probiotic depends on why you are taking it. If the primary purpose for taking the probiotic is to aid digestion, then you must take it with meals. If the goal is to have the probiotic reach the lower intestinal tract, then it may be more appropriate to take it between meals, with a full glass of water. Water dilutes the stomach acids and moves the organisms quickly into the intestinal tract. Probiotics can also be used for both purposes by taking some with meals and some between meals⁽¹⁴⁾. We suggest taking probiotics first thing in the morning and at bedtime, with water.

There will, inevitably, be some loss of activity of probiotics during the passage from stomach to colon, due to pH, bile acids and other factors. Successful colonization depends very much on optimal dosing and can be very strain dependent. That is the reason a high potency multi-strain formulation such as our Adult Formula CP-1 and probiotic powders become effective. The gastrointestinal tract harbors about 100 trillion bacteria, more than 90% in the colon. The intake of merely a few billion probiotic ‘friendly bacteria’ a day is unlikely to make much of a difference in most instances. Also please note that our probiotic strains are very much acid resistant.

OUR PRODUCTS SHOULD BE REFRIGERATED TO RETAIN MAXIMUM POTENCY. Keeping our product at room temperature for 2-3 weeks, however, will have little impact on the bacterial count. We have studied the effect of temperature on our CP-1 capsules. Storing one bottle in an un-air-conditioned room, in the summer, for five months, resulted in bacterial count reduction from 60 billion cfu's per capsule to 30 billion cfu's per capsule, indicating very good temperature stability of our probiotics.


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