THE SCIENCE OF PROBIOTICS
NOHA Oak Park lecture by Carlos Reynes, MD, on 2/8/2005

Carlos M. Reynes, MD, is a Board Certified Internal Medicine Specialist. He has pricticed medicine in the west Chicago suburbs since 1991 and since 1997 has been a Clinical Professor of Medicine at the University of Illinois. He is a member of the American College for the Advancement in Medicine and the Institute for Functional Medicine and has studied alternative/integrative medicine for the last eight years. He is the founder and medical director of the Integrative Therapies Medical Center in Oak Park. He can be reached at (708) 358-0111 or online at www.integrativetherapies.medem.com


The Science of Probiotics is a rapidly growing field and probiotics are found in most health food stores. In 2003, sales were 12.9 million dollars, expanding at the rate of 14% per year. Probiotics have moved from position number ten in 2000 to position number five in 2005 in importance in food formulation. Farmers have been using probiotics since the 1970s to help disease resistance, increase reproduction, improve milk yield, and egg production. Funding for probiotic research has been doubling annually since 1996.

What are probiotics? The definition is: living micro-organisms that, when ingested or locally applied in sufficient numbers, can fill one or more specified demonstrated functional or health benefits for the consumer. Bulgarians were noticed to live longer and they used microbiotics to ferment milk and kefir. Stool analysis showed Lactobacillus bulgaricus in the healthy, long-living Bulgarians.


Farmers have been using probiotics since the 1970s to help disease resistance, increase reproduction, improve milk yield, and egg production.

"Death begins in the colon" because people without enough healthy microorganisms in their colon will get many different diseases. There are 500 species of bacteria living within you. Thirty to forty species represent about 99% of everyone's micro flora. One hundred trillion bacteria live within you, more than there are cells in your body, but weigh only two to three pounds.

A good healthy colon can be compared to natural prairie with many different wild plants all-growing in natural ecological balance. This is bowel ecology. How does your "garden" grow?

Within your GI tract there are few bacteria in your stomach due to the extreme acids. Most of your bacteria live much further down in your colon where the acidity is much lower.

It is good to maintain a balance between the "good" and the "bad" bacteria. A healthy person has about 85% good and 15% bad bacteria. The word eubiosis means balanced while dysbiosis means unbalanced. Antibiotics, non-steroidal anti-inflammatory medications, etc., geographic location, race, diet, aging, or illness can upset this balance.


[Probiotics are] living micro-organisms that, when ingested or locally applied in sufficient numbers, can fill one or more specified demonstrated functional or health benefits for the consumer. Bulgarians were noticed to live longer and they used microbiotics to ferment milk and kefir.

If infants are vaginally delivered, nursed or breast-fed by their mothers, they get their mother's bacteria. However, infants who are born by caesarean section and bottle-fed only formula, do not get these beneficial bacteria. These caesarean section infants do get a chance to "catch up" later.

Symptoms of Dysbiosis can include:

Dysbiosis has been implicated in all the following conditions:

Tests for dysbiosis include stool analyses that measure beneficial and harmful bacteria, yeast or parasites. Urine tests that measure metabolic markers for dysbiosis can also be done.

How do we prevent or treat dysbiosis? We need to work on bowel ecology. This includes what many practitioners regard as a 4 "R" program:

  1. Remove toxins; including food allergies, parasites, yeast,
  2. Replace stomach acid, digestive enzymes,
  3. Repopulate with the good bacteria, and
  4. Repair the bowel lining.

How do Probiotics Work? They:

Benefits Associated with Probiotic Use include:

Probiotic Use in Diarrhea:
A review of nine studies on the effect of Lactobacillus as therapy for diarrhea in children concluded that: "Lactobacillus is safe and effective as a treatment for children with acute infectious diarrhea" (Van Niel et al, Pediatrics 109:678-84, 2002).

Furthermore other studies have shown probiotics to be effective in antibiotic associated diarrhea and in "traveler's diarrhea." What is traveler's diarrhea? Your life is good and you feel great then you take a trip to possibly Mexico and have a lot of diarrhea. After you return the diarrhea remains and you feel rotten with many Dysbiosis type symptoms. In a 2002 study, Saccharomyces boulardi helped prevented traveler's diarrhea 70% of the time vs. 31% in the placebo group. You should consider taking a probiotic before you go.


"Death begins in the colon" because people without enough healthy microorganisms in their colon will get many different diseases.

For prevention of antibiotic associated intestinal symptoms consider that antibiotics kill beneficial as well as bad bacteria. This can cause an imbalance in the bowel ecology, which can result in diarrhea.

In one study when Ampicillin was combined with the beneficial bacteria Lactobacillus acidophilus, 8.3% of the patients got diarrhea vs 21% of the patients that took Ampicillin without the benefits of a probiotic. This study does not claim that Lactobacillus is a guaranteed "cure" for diarrhea, only that it may help reduce the incidence of diarrhea caused by the use of Ampicillin.

There is also radiation-induced diarrhea from using radiation for colon or bladder cancer. Radiation impairs the microsal lining of the colon. For radiation-induced diarrhea, use the probiotic VSL#3. In a test of 95 patients, 55% with the placebo had radiation diarrhea, while 38% with VSL#3 got better.


[S. Boulardii] has been proven in studies to reduce the incidence of "travelers' diarrhea" and significantly reduce the duration of acute diarrhea and was also effective in treating chronic diarrhea in AIDS patients.

Limited studies have suggested that L. plantarum and Lactobacillus GG may be helpful in eliminating the symptoms of small bowel bacterial overgrowth. Lactobacillus has been shown to be antagonistic to Helicobacter pylori (the bacteria that is known to cause ulcers and inflammation of the stomach) both in vitro and in mice experiments. The results of studies with Lactobacillus that have been performed in humans are conflicting, with some showing modest protection and others showing no protection. One study using L. acidophilus strain CRL 639 killed all H. pylori in 48 hours.

Hypertension
Not very many studies have been done yet, but one fermented milk product reduced systolic blood pressure by ten to twenty points. We want to know more now but should wait for the future in this area.

For Cancer, Probiotics or Beneficial Bacteria can:

Probiotics can help Immune Function.
Probiotic organisms can directly or indirectly influence mucosal and systemic immune function by altering cytokine gene expression, antibody production, and by modulating cellular immune responses. Probiotics can increase intestinal immunoglobulin A levels, increase "T" cells that help with the immune system, and can turn off cytokine genes that produce inflammatory molecules.


In a study of 571 children, ages 1 to 6, after 7 months the children who took Lactobacillus GG had significantly fewer respiratory infections.

In a study of 571 children, ages 1 to 6, after 7 months the children who took Lactobacillus GG had significantly fewer respiratory infections. New probiotic studies are revealing new information every day, particularly about the immune system. Even a non-living probiotic helped the immune inflammatory response. The gut has a "toll light receptor" that acts as a doorkeeper and lets only the good bacteria in.

Probiotics vs. Inflammation
It is known that over expression of COX2 is indicative of inflammation and cancer. COX 1 is associated with GI integrity and is a housekeeping enzyme. Acidophilus and Bifidobacterium were assayed for their ability to exert an effect on these genes. The latter showed a three-fold increase of COX1/COX2 ratios signifying a shift in the ratio towards a healthy expression profile. In other words, COX2 was down regulated and COX1 was up regulated

Saccharomyces Boulardii reduces the growth of Candida albicans ( 10-50 fold), E coli, Shigella, Salmonella, Pseudomonas and Staphylococcus. It has been proven in studies to reduce the incidence of "travelers' diarrhea" and significantly reduce the duration of acute diarrhea and was also effective in treating chronic diarrhea in AIDS patients. When added to vancomycin treatment for Clostridium difficile siginificantly reduced the number of relapses.


While a low-dose probiotic can be great for a general maintenance program, oftentimes a much higher dose is required to achieve clinical significance.

In a study of 20 patients with active moderate Crohn disease randomly assigned to received either S. Boulardi or a placebo for 7 weeks. A significant reduction in the frequency of bowel movements and in disease activity was observed in the group receiving the S. Boulardii but not in the placebo group.

Ulcerative Colitis
In an open-label pilot trial with S. boulardii, a group of 25 patients with mild to moderate ulcerative colitis received S. boulardii for 4 weeks in addition to the treatment with mesalamine. Of the 24 patients who completed the study, 17 attained clinical remission.

Who should take Probiotics?
The use of probiotics should definitely be considered in the following circumstances:

  1. During and After taking Antibiotics,
  2. For symptoms of Dysbiosis, including Irritable Bowel Syndrome, and
  3. To prevent or treat Diarrhea

Desired Probiotic Characteristics
Experts in the filed of probiotics have identified features that probiotics need to be effective. Probiotics should be non-pathogenic and non-toxic, of human origin, resistant to gastric acid, and bile, have the ability to attach to intestinal cells, at least temporarily colonize the intestinal tract, be able to adapt to native intestinal flora, produce antimicrobial substances, and have some documented beneficial effect to the host.

What to Consider When Using:
The recommended daily intake for probiotic supplements can range fro 1 billion units (sometimes referred to as colony forming units, or CFU's) to 100 billion units per day. These amounts may be written on the label as 1 x 109 or 109 for one billion units, and 1 x 1010 or 1010 for ten billion units. While a low-dose probiotic can be great for a general maintenance program, oftentimes a much higher dose is required to achieve clinical significance. Additionally the inclusion of multiple strains may be beneficial for specific conditions.


While many products make claims regarding the number of organisms in the product, these typically refer to the numbers at the time manufacture, which can be very different from the amount still viable at the time of purchase. Exposure to heat, moisture, and oxygen can all negatively affect survival of probiotics in a product . . .

While many products make claims regarding the number of organisms in the product, these typically refer to the numbers at the time manufacture, which can be very different from the amount still viable at the time of purchase. Exposure to heat, moisture, and oxygen can all negatively affect survival of probiotics in a product, so the expiration date is especially important to consider when buying products. Some products have an enteric coating, because certain probiotic bacteria need protection in order to survive exposure to gastric fluid. In general, Lactobacillus, Bifidobacterium, and Streptococcus species do not need enteric coating as they can survive passage through the stomach. However, L. bulgaricus and S. thermophilus, as well as Leuconostoc and Lactococcus species, cannot survive passage through the stomach. These bacteria are commonly found in yogurt because they are used as starters for dairy products. However, they do not colonize the intestinal tract; so they are likely to have little effect as probiotics. Some bacteria naturally sporulate ("hibernate" within a protective coating) when they are exposed to harsh conditions, and some researchers postulate that sporulated bacteria are more resistant to the harsh conditions found in the intestinal tract. Consequently, another delivery method is to manufacture probiotics in the form of bacterial spores — this is most often used for bacteria of the genus Bacillus.


ConsumerLab.com found that 8 of the products contained less than 1% of the claimed number of live bacteria or of the expected minimum of 1 billion. In fact, six products had only a few thousand live bacteria. . . . It is quite likely that products that were low in bacteria may not work.

For the treatment of diarrhea, it is recommended to start taking probiotic supplements as soon as symptoms appear. However, if symptoms persist for several days, see a physician. If you are taking antibiotics, it may be advisable to take them at least 2 hours apart from taking a probiotic, as the antibiotic could potentially kill the organisms. Following antibiotic treatment, take probiotic supplements for 2 weeks. Probiotics are sometimes taken before travel in an attempt to prevent traveler's diarrhea. To gain probiotic benefits from yogurt or other dairy foods, look for products labeled "contains live cultures" or "active cultures". Some yogurts may also state the species of bacteria they contain. For treating vaginal yeast infections, vaginal suppositories containing approximately 1 billion Lactobacillus organisms are typically used.

You Can't Always Get what you Want
On testing, ConsumerLab.com found that 8 of the products contained less than 1% of the claimed number of live bacteria or of the expected minimum of 1 billion. In fact, six products had only a few thousand live bacteria. Interestingly, products that did not claim a specific number of live bacteria at the time of use were much more likely to have been low, while 7 of the 8 products that gave expected numbers at the time of use (not limited to the time of manufacture) met these counts. It is quite likely that products that were low in bacteria may not work. This was an early study and later ones aren't nearly as bad, but it would still be a good idea to check any probiotic on the Internet. A good website to start checking on probiotics and other supplements is: www.consumerlabs.com . There is a yearly fee.

Look at the Labels:
According to the National Nutritional Food Association, labels for probiotics should give:

  1. The micro-organism identified by its genus and species
  2. A statement of the minimum number of viable cells
  3. The expiration date or "best before . . ."
  4. Storage recommendations - should it be refrigerated? If so, how long can it be kept out of the refrigerator before it dies?

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Bibliography


Article from NOHA NEWS, Vol. XXXI, No. 2, Spring 2006, pages 1-4