Lactobacillus GG

Breakthrough Probiotic Clinically Proven to Support Gastrointestinal Health

By Jim English and Ward Dean, MD

Over the past several years the relationship of the health of the intestinal tract to the overall health of the body has become increasingly appreciated. The human gastrointestinal (GI) tract is home to a vast and complex bacterial ecosystem, hosting over 400 different species. (1,2) The GI tract in a healthy adult is about 30 feet long and contains anywhere from 5 to 15 pounds of living bacteria. In healthy individuals the most common of these organisms includes Escherichia coli, Klebsiella, Streptococcus, Lactobacillus, Staphylococcus, Bacillus, Bifidobacterium, Fusobacterium, Clostridium, Eubacterium Peptococcus, and Peptostreptoccus. In terms of sheer numbers, the human intestinal tract contains ten times as many bacterial cells as there are tissue cells in the entire body.

These gut microflora play a vital role in human health and perform important metabolic functions that support the digestive system. Research reveals that the gut lining is primarily nourished by nutrients produced from favorable bacteria – not by our blood supply, as was previously believed. We are completely reliant upon the activities of these bacteria for the manufacture of key vitamins, the assimilation and distribution of nutrients, and for the suppression of pathogenic and putrefactive bacteria.

For example, bacterial fermentation, a vital component of our digestive process, produces essential nutrients. Beneficial bacteria are also the primary source of short chain fatty acids. Without bacteria to produce these nutrients, cell damage can also occur, leading to a loss of function in the gut lining. Consequently, maintenance of the proper balance of bacteria in the gut is vital to good health.

A Delicate Balance 

Factors that can upset the delicate balance of the GI tract include:

• Overgrowth of undesirable bacteria
• Overgrowth of yeast, including candida
• Parasites, such as amoebas
• Viral illnesses, such as measles
• Bad water or poor hygiene
• Too many sweets or starchy foods
• Too many alcoholic beverages
• Food allergies
• Certain medical drugs
• Frequent use of antibiotics
• Exposure to radiation
• Surgical complications
• Physical injury
• Excessive stress
• Environmental toxins
• Genetic sensitivities to any of the above

The Gut Mucosal Barrier 

Gut microflora play an important role in the intestine’s defense barrier. In the absence of a healthy intestinal microflora, antigen transport is increased, leading to allergies and increased allergic sensitivity. (3)

Most antigens in the diet are excluded from the body by a well-functioning intestinal mucosal barrier. (4) However, a fraction of these can bypass this barrier in even the healthiest of people. The antigens are absorbed across the epithelial layer by a process called transcytosis. Transcytosis operates along two pathways. (4,5) The main, or degradative, pathway involves lysosomal processing of the proteins into smaller peptide fragments. This reduces the immunogenicity of the proteins, thereby diminishing the antigen load. This is important in maintaining the host-defense system. Another pathway (paracellular leakage) allows for the transport of intact proteins, a process that can result in antigen-specific immune responses.

Paracellular leakage of macromolecules does not occur in a healthy gastrointestinal tract because of intact, tight intracellular junctions which maintain the macromolecular barrier. Consequently, in healthy people, antigen transfer is well-controlled, and aberrant antigen absorption does not occur.

Leaky Gut Syndrome

A large body of literature now describes the phenomenon known as “leaky gut,” a syndrome characterized by abnormal permeability of the intestines to potentially toxic or antigenic materials. Inflammatory bowel disease, alcoholism, rheumatic conditions involving the gut, allergic disorders, and a variety of other problems appear to be associated with abnormal gut permeability.

Bacterial Translocation

A phenomenon related to leaky gut syndrome is that of bacterial translocation, whereby whole bacteria or bacterial poisons (endotoxins) pass through the gastrointestinal walls and are absorbed by the lymph glands, liver, lungs and other organs. This bacterial translocation and the associated absorption of endotoxins can result in multiple organ stress and dysfunction.
A variety of natural substances have been shown in experimental and clinical studies to enhance the protective and barrier functions of the gut walls, and hence to diminish hyperpermeability and bacterial translocation.

Functional Foods and Probiotics 

A functional food is defined as a specialized food product that can promote human health and well-being better than a similar traditional food. The most widely used and recognized functional food is yogurt, a product made by fermenting milk with bacteria. Prior to the discovery of specific microbial pathogens, scientists recognized that the intestinal flora could be improved by the ingestion of yogurt. For centuries, medical practitioners counted on fermented dairy products to ease various intestinal disorders – especially diarrhea.

The newest, and perhaps the most important group of foods in the category of functional foods are the probiotics. Probiotic is a Greek word which means “for life.” It is used to describe the “friendly” bacteria that normally live in the intestinal tract and which contribute to good health. Unfortunately, probiotics can be destroyed or depleted by stress, aging, antibiotics, changes in one’s diet, or ingestion of foreign bacteria (often contracted while traveling in foreign countries). Probiotics is also a label for food products that contain health-promoting bacteria – primarily lactic-acid bacteria (LAB) that have a positive influence on the metabolic activity of the intestinal flora.

At the turn of the century, the Russian researcher, Dr. Élie Metchnikoff suggested that the aging process could be mitigated by altering the intestinal flora through the consumption of lactobacillus-rich yogurt. In 1905, Metchnikoff conducted original research that led to our first knowledge of Lactobacillus strains. Metchnikoff introduced Lactobacillus bulgaricus (L. bulgaricus) into the production of fermented milk. Consequently L. bulgaricus became the standard starter strain, along with Streptococcus thermophilus, for yogurt throughout the world (Metchnikoff E. The Prolongation of Life: Optimistic Studies. New York: G.P. Putnam’s Sons 1908).

While Metchnikoff’s discovery aided in the treatment of many intestinal disorders, the two strains of bacteria that he used did not provide the degree of benefit he had hypothesized, partially due to the inability of these strains to colonize the human intestinal tract. These strains are sensitive to acid conditions, and are easily destroyed in the stomach. Additionally, these bacterial species do not normally inhabit the human gut.

Unique “Native” Bacterium in Human GI Tract 

Lactobacilli constitute a major part of the microflora throughout the gastrointestinal tract. These bacteria have been proposed as candidate probiotic microorganisms to reinforce the barrier effect in the gut. Consumption of probiotic bacteria can alleviate intestinal inflammation, normalize increased intestinal permeability, and strengthen the intestine’s immunologic barrier function. (6,7) The most exciting of these materials is a new breakthrough probiotic supplement, Culturelle™, (Lactobacillus GG).

Lactobacillus GG (Lactobacillus G.G., strain ATCC 53103) is a bacterium that occurs naturally in the human digestive tract. This strain of bacteria was first isolated by two Boston scientists, Professors Sherwood Gorbach and Barry Goldin, who were searching for a strain of lactobacillus that could colonize the human intestine and thereby exert the beneficial effects which Metchnikoff had hoped to produce by his yogurt cultures. As guides for their research, Gorbach and Goldin established a number of criteria which they believed their ideal probiotic candidate should satisfy. The bacterium would be:

1. Of human origin;
2. Capable of attaching to human intestinal (epithelial) cells and colonizing the gut to prevent competition from invading pathogens;
3. Resistant to acid and bile, able to survive transit from the stomach to the intestines;
4. Exhibit beneficial, health-promoting activity in the host system; and
5. Exhibit a high degree of safety.

In 1985, Gorbach and Goldin isolated their ideal probiotic “bug,” which was designated, appropriately, Lactobacillus GG (LGG). Today, LGG is the best-studied and most extensively documented probiotic lactic-acid bacteria strain in the world. This strain stabilizes human intestinal microflora and hastens the removal of pathogenic microorganisms. Its beneficial effects in treating gastrointestinal disorders and bacterial and viral infections are extremely well documented, as is its ability to strengthen the immune system. In addition to ongoing studies of LGG’s ability to prevent gastrointestinal infections, some interesting preliminary observations on the antitumor effect of LGG in the colon have also been reported. In Japan, a dairy product containing LGG is the first – and only – food specified for probiotic use.

Treatment of Acute Diarrhea 

Lactobacillus GG (LGG) has shown promising results in treating diarrhea caused by viruses and bacteria in both adults and children. Measurements of the intestinal microflora show that LGG adheres to the intestinal wall during healthy periods as well as during episodes of diarrhea. In addition, LGG improves microflora balance, and normalizes fecal enzyme and short-chain fatty acid levels.

Safety of LGG 

The safety assessment of Lactobacillus GG covers traditional toxicity tests and studies on the safety of the GG strain in both in vivo and in vitro conditions. A number of studies in different clinical conditions, including human volunteer studies and epidemiologic surveillance indicate that the strain is safe for human consumption, even in large amounts. At present, Lactobacillus GG has the most extensive safety assessment record of any other probiotic strain.

In Vitro Studies 

The local effects of lactic-acid bacteria on the intestine are commonly measured by their in vitro ability to adhere to human intestinal cell walls and to degrade protective intestinal mucus. These tests provide an indirect measure of the potential of lactic-acid bacteria to invade intestinal cells and to damage the protective glycoproteins of the intestinal mucus. A large number of studies have been conducted with different strains of lactic-acid bacteria.Lactobacillus GG showed no invasive properties, even though the strain is strongly adherent to human intestinal cell lines. (10)

Probiotic strains that do not degrade intestinal mucus or its glycoproteins are likely to be noninvasive and beneficial to the intestinal epithelium. In a recent study, commercial probiotic strains – including Lactobacillus GG – were shown to be inactive in mucosal degradation injury. In earlier studies, some fecal Bifidobacteria were found to degrade mucus. (8)

Production of antimicrobial compounds and inhibition of pathogen growth by lactic-acid bacteria has been assessed in vitro. Data from these tests support the safety of Lactobacillus GG and indicate that the strain decreases intestinal pH and reduces the numbers of pathogenic bacteria in the intestinal tract thus protecting the host. (9,10)

In the most recent safety-related study, Lactobacillus GG was observed to slow down the development of dimethyl hydrazine-induced colon tumors in rats on a high-fat diet. (11) Similarly, Lactobacillus GG decreased alcohol toxicity in mice, dramatically reducing plasma endotoxin levels. (12)

Clinical Studies 

Data from clinical trials in human volunteers also attest to the safety of Lactobacillus GG. These studies included: short-term trials in over 2,000 healthy normal volunteers; studies to determine the efficacy of LGG in preventing and treating acute diarrhea in premature infants, (l3) infants, (l4,15) and children with diarrhea; (12,l3,16) studies on immune effects; (16) and studies in patients with severe intestinal infections. (8)

A summary from the literature of safety studies and reported effects indicate that no harmful effects have been observed in controlled clinical studies with Lactobacillus GG. To the contrary, during treatment of intestinal infections, beneficial effects have been observed, including stabilization of the gut mucosal barrier, prevention of diarrhea, and amelioration of infant and antibiotic-associated diarrhea and intestinal inflammation.

A study from Peru indicates the ability of LGG to colonize the intestinal tract of children. In this study, LGG was administered in a lyophilized form which was sprinkled on Jello. (17) LGG was recovered from the stools of eight of 11 children, and in six cases it was recovered on multiple occasions.

Childhood Diarrhea 

Childhood diarrhea is a common disorder around the world, in both developed and developing countries. The incidence of childhood diarrhea varies from two to three episodes per year in economically advanced countries, to twice that number in developing countries. In the developing countries, childhood diarrhea is usually associated with acute weight loss and high mortality. Effective treatment of diarrhea with LGG has been reported in two studies from developing countries (Pakistan and Thailand), and in one each from a Baltic country (Estonia) and a European country (Italy).

LGG and Antibiotic Associated Diarrhea 

Many antibiotics produce serious gastrointestinal side effects. Erythromycin, especially, is a frequent cause of such problems. In a study by Siitonen et al., (15,18) two groups of healthy volunteers took a moderate dose of erythromycin – 400 mg, three times daily for 7 days. One group received LGG-containing yogurt, while the control group was given conventional pasteurized yogurt. The number of daily bowel movements was fewer, the duration of diarrhea was shorter, and the frequency of stomach pain, abdominal pain, and nausea were significantly reduced in the LGG group. Fecal counts of LGG during erythromycin administration revealed that 75% of the volunteers had detectable levels of LGG despite the use of an antibiotic that is active against LGG in vitro. Several investigations are currently being conducted on childhood diarrhea in Europe and developing countries. The results that have been published thus far provide convincing evidence that LGG is beneficial in reducing the time-course and the symptoms of acute diarrhea in children.

Conclusion 

LGG continues to be extensively researched around the world, with many more treatment and prevention trials currently underway. Thus, more data will be forthcoming in the near future. Rather than wait for the final conclusive results to be reported, we believe that adequate studies have been performed to indicate that LGG is a safe, highly effective nutritional substance for a wide variety of clinical conditions, to include intestinal disorders – especially a number of forms of diarrhea, including rotavirus diarrhea in children, bacterial diarrhea in children and adults, travelers’ diarrhea, antibiotic-associated diarrhea, and C. difficile relapsing diarrhea and colitis in children and adults. Measurements of the intestinal microflora show intestinal implantation of LGG during healthy periods and during diarrhea episodes, as well as improvements in microflora balance and of flora function.

References

1. Finegold SM, Attebery HR, Sutter VL. Effect of diet on human fecal flora: Comparison of Japanese and American Diets. Am J Clin Nutr 1974;27:1546-69
2. Moore WEC, Holderman LV. Human fecal flora: Comparison of Japanese and American diets. Appl Microbiol 1974;27:961-79.
3. Heyman M, Gorthier G, Petit A, Meslin J-C, Moreau C, Desjeux J-F. Intestinal absorption of macromolecules during viral enteritis: An experimental study on rotavirus-infected conventional and germ-free mice. Pediatr Res 19887; 22:72-8.
4. Heyman M, Grasset E, Duroc R, Desjeux JF. Antigen absorption by the jejunal epithelium of children with cow’s milk allergy. Pediatr Res 1988;24:197-202
5. Majamaa H, Isolauri E. Evaluation of gut mucosal barrier: Evidence for increased antigen transfer in children with atopic eczema. J Allergy Clin Immunol 1996;97:985-90.
6. Kaila M, Isolauri E, Soppi E, Virtanen E, Laine S, Arvilommi H. Enhancement of the circulating antibody secreting cell response in human diarrhea by a human Lactobacillus strain. Pediatr Res 1992;32:141-4.
7. Isolauri E, Majamaa H, Arvola T, Rantala I, Virtantn E, Arvilommi H. Lactobacillus casei strain GG reverses increased intestinal permeability induced by cow milk in suckling rats. Gastroenterology 1993;105:1643-50.
8. Hoskins LC, Augustines M, McKee WB, Boulding ET, Kriaris M, Niedermeyer G. Mucin degradation in human colon ecosystems: Isolation and properties of fecal strains that degrade ABH blood group antigens and oligosaccharides from mucin glycoproteins. J Clin Invest 1985;75:977-53.
9. Coconnier MH, Klaenhammer TR, Kerneis S, Bernet MF, Servin A. Protein-mediated adhesion of Lactobacillus acidophilus BG2F04 on human enterocyte and mucus-secreting cell lines in culture. Appl Environ Microbiol 1992;58:2034-9.
10. Elo S, Saxelin M, Salminen S. Attachment of Lactobacillus casei strain GG to human colon carcinoma cell line Caco-2: Comparison with other dairy strains. Lett Appl Microbiol 1991;13:154-6
11. Goldin B, Gualtieri L, Moore R. The effect of feeding Lactobacillus GG on the initiation and promotion of dimethylhydrazine-induced intestinal tumors in the rat. Nutr Cancer 1996;25:197-204.
12. Namji AA, Khettry U, Sadrzadeh S. Lactobacillus feeding reduces endotoxemia and severity of experimental alcoholic liver disease. Proc Soc Exp Biol Med 1994;205:243-7.
13. Millar MR, Bacon C, Smith SL, Walker V, Hall MA. Enteral feeding of premature infants with Lactobacillus GG. Arch Dis Child 1993;69:483-7
14. Seep E, Mikelsaar M, Salminen S. Effect of administration of Lactobacillus casei strain GG on the gastrointestinal microbiota of newborns. Microbial Ecol Health Dis 1993;6:309-14.
15. Majamaa H, Isolauri E, Saxelin M, Vesikari T. Lactic acid bacteria in the treatment of acute rotavirus gastroenteritis. J Pediatr Gastroenterol Nutr 1995;20:333-8.
16. Isolauri E, Juntunen M, Rautanen T, Sillanaukee P, Koivula T. A human Lactobacillus strain (Lactobacillus casei sp strain GG) promotes recovery from acute diarrhea in children. Pediatrics 1991;88:90-7.
17. Sheen P, Oberhelman RA, Gilman RH, Cabrera L, Versategui M, Madico G. Short report: a placebo-controlled study of Lactobacillus GG colonization in one- to three-year-old Peruvian children. Am J Trop Med Hyg 1995;52-389-92.
18. Biller JA, Katz AJ, Flores AF, Buie TM, Gorbach SL. Treatment of recurrent Clostridium difficile colitis with Lactobacillus GG. J Pediatr Gastroenterol Nutr 1995;21:224-6.