Lactobacillus Acidophilus

Description

At least 400 different species of microorganisms inhabit the human gastrointestinal tract. Enteropathogenic microorganisms cause disease in the individual; symbiotic or "good" microorganisms actually benefit the individual by their presence.

Lactobacillus bacteria are considered "good bacteria". That is, when present, lactobacilli produce beneficial metabolic by-products, inhibit the growth of pathogenic bacteria and stimulate the immune system of the human host.

The following lactobacilli are normal inhabitants of the human intestinal tract:

L. acidophilus	L. bifidus
L. casei	L. fermentum
L. salivaroes	L. brevis
L. leishmannii	L. platnarum
L. cellobiosus

L. acidophilus is an anaerobic gram-positive bacterium, which requires vitamin B complex vitamins and amino acids for growth and produces only lactic acid as its fermentation end product. L. acidophilus is found virtually throughout the gastrointestinal tract, even in the highly acidic stomach.

Infants are born with a sterile gastrointestinal tract, but become colonized by lactobacilli shortly after birth. Analysis of an infant's feces will demonstrate large quantities of lactobacilli. However, as the infant is exposed to bacteria in the environment, the gut also becomes colonized with other species of bacteria, including pathogenic gram-negative bacteria.

Some researchers believe that beneficial levels of lactobacilli can be maintained in the gut through ingestion of foods rich in lactobacilli or supplementation with nutritional products containing the bacteria. L. acidophilus is found in a wide variety of dairy products and can be found in the human oral cavity and in the feces if dairy products are consumed. Yogurt and other cultured milk products containing L. acidophilus are suggested for maintaining a healthy amount of L. acidophilus in the gut.

Supplementation with Lactobacillus acidophilus has been advocated as a result of several important observations. First, the incidence of colon cancer is higher among North Americans and Western Europeans than among residents of Africa, Asia or South America. Although the lower incidence may be attributable to a diet higher in fiber, it may also stem from a diet higher in products containing L. acidophilus.

In animal studies, when grain-fed rats were supplemented with L. acidophilus, little change occurred in the metabolic activity of fecal bacterial enzymes. However, when meat-fed rats were supplemented, the activities of potentially carcinogenic bacterial enzymes, in particular, beta-glucuronidase, azoreductase and nitroreductase, were significantly reduced. Similar effects were observed in human trials. In vegetarians, the addition of L. acidophilus supplements had little effect on fecal bacterial enzymes, which were already low. By comparison, when meat-eating humans were supplemented, the activity of these potentially carcinogenic enzymes was reduced.

L. acidophilus also helps restore the equilibrium of the gut microflora which has been disrupted by the use of antibiotics. Antibiotics, although lifesaving in their ability to kill pathogenic bacteria, also kill desirable gut microorganisms such as lactobacilli. There is growing evidence L. acidophilus supplementation can exert a positive immunomodulating effect, correcting antibiotic-induced microflora imbalances.

A controversy exists regarding which species and strains of lactobacilli are most beneficial to humans. In 1915, a scientist reported Lactobacillus bulgaricus could be maintained in the intestine of humans only for very short periods of time (up to 12 days). This finding suggested L. bulgaricus offered only temporary benefit for recolonizing the gut with lactobacilli.

Over 50 years later, another group of scientists reported L. acidophilus from human infants had failed to colonize the gut of chickens. However, another strain of L. acidophilus, isolated from the digestive tract of chickens grown in a germ-free environment, successfully colonized the gut of ordinary chickens. These interesting findings suggest different strains of L. acidophilus have specific affinities for particular animal species.

As a result of these and other observations about the species specificity of particular strains of L. acidophilus, Shahani and Ayebo proposed in 1980 lactobacilli used for dietary supplementation, including all of the lactobacilli listed above, should possess the following basic qualities:

1. They should be normal inhabitants of the host intestine or be capable of adapting to the host intestinal environment;

2. They must survive passage into the intestine and be capable of establishing in the intestine, particularly the small intestine where physiological activities associated with digestion and absorption of nutrients would be expected to occur;

3. They must perform functions advantageous to the host;

4. The addition of the culture should not be detrimental to the quality of the food, and neither should the food nor the method by which it is processed harm the culture.

Three considerations should be weighed when choosing a L. acidophilus enriched-product:

1. Benefits associated with one particular strain may not necessarily apply to other strains of the same organism.

2. Commercial preparations of cultures shown to be effective in the laboratory may not contain sufficient numbers of viable microorganisms to be of any clinical benefit; and,

3. Lactobacilli are fastidious in growth and metabolism, and are thus affected by alcohol, antibiotics and other elements of the diet.

Viability
The number of colony forming units (cfu) per unit of weight (g) should be determinable for each product purchased. The label should contain information on the product's cfu/g and any results of viability tests. The number of cfu/g should not be less than two billion in the case of L. acidophilus. The recommended test of viability is that of Collins (1978), using media with and without 0.2% oxgall (bile test). The product should include not only the cfu/g information but also the results of the oxgall test, expressed as the ratio of bile resistant cfu/g to total cfu/g. A high ratio indicates high viability of the L. acidophilus in the gastrointestinal tract.

Strain
Kleeman and Klaenhammer have reviewed the need to select strains that can survive and colonize the hostile environment of the gastrointestinal tract. A multinational study of the survival of various lactobacilli in humans found that the L. acidophilus ADH strain survived better and adhered better than other strains tested. Additionally, they found that the addition of milk or any cultured milk product optimized the levels of L. acidophilus within the digestive tract.

Johnson et.al., have recently reported on the selection of L. acidophilus strains for use in "acidophilus products." Recent studies of DNA-DNA hybridization have revealed L. acidophilus strains can be divided into several groups, of which only one group should be classified as L. acidophilus.

This latter group consists of bacterial strains which meet the desirable minimal criteria for L. acidophilus and are also grown in a media containing lactose (milk sugar) for greatest effectiveness. Among the desirable characteristics of L. acidophilus strains for use as dietary supplements is their ability to rapidly hydrolyse lactose and produce acid. In studies of various strains of L. acidophilus, the strains from the A1 (same as Ia) homology group, particularly, strains NCDO 1748 (ATCC 4356) and VPI 0328 (ATCC 4355), were found to meet the criteria for use as dietary adjuncts. However, this does not preclude there are other proprietary strains of L. acidophilus with even higher levels of desirable characteristics.

Packaging of Product
Considerable attention must be paid to the packaging and storing technique used by the manufacturer to insure the product contains a viable bacterial culture that is therapeutically beneficial, has little moisture and free of contamination. Even the temperature at the time of packaging affect the viability and therapeutic usefulness of the culture.

Sarles et.al., reported as early as 1951 that lactic acid-producing microorganisms, such as acidophilus, will die rapidly when stored at room temperature (usually 70-72 degrees F or 21 degrees C). Thus, the material should be stored and transported at temperatures no higher than 60 degrees F (15 degrees C). Because homes and offices are often kept warmer than 60 degrees, it is imperative that the product be refrigerated at all times.

L. acidiophilus should be sold in dark amber glass containers, which minimize the culture's exposure to potentially harmful moisture, oxygen and light. Indeed, most lactobacillus supplements are found in a store's refrigeration section as freeze-dried powders packed in glass amber jars. Many yogurts and dairy products may also contain other beneficial microorganisms, such as L. bulgaricus, S. thermophilus, B. adolescentis, or B. bifidus.

Since pasteurization kills lactobacilli, yogurt and other dairy products cultured before pasteurization are useless as sources of L. acidophilus or other beneficial microorganisms. When selecting a yogurt or some other dairy product, therefore the buyer should verify the products were cultured after pasteurization.

L. bulgaricus, a common component to yogurt, produces hydrogen peroxide during the manufacture and storage of the product. If L. acidophilus is combined with L. bulgaricus, it should be noted the hydrogen peroxide will cause a decrease in the numbers of L. acidophilus. This antagonistic reaction can be markedly decreased by adding catalase to the yogurt at the time of manufacture.

Method of Action

Lactobacilli are able to producce bacteriocidal (bacterocins) or antimicrobial activity against many food-borne pathogens, including :

Proteus	Escherichia
Staphylococcus	Bacillus
Streptococcus

L. acidophilus produces lactic acid and hydrogen peroxide. Bacterocins are "antibiotic-like" substances and bactercidal proteins. However, they are not antibiotics, as is frequently claimed in promotional literature for lactobacilli and other lactic acid productin bacteria.

L. acidophilus (and L. lactis) have been shown to produce enough hydrogen peroxide to inhibit the growth of the S. aureus micropathogen, even at temperatures as low as 5 degrees C. However, L. acidophilus require folic acid and riboflavin, two B vitamins, to produce hydrogen peroxide. If either of these vitamins is in too short of a supply, to will effect the ability of the lactobacilli to produce this agent. However, riboflavin deficiencies are very rare. Other antimicrobial substances lactobacilli are believed to synthesize include acetic acid and benzoic acid.

Lactobacillus is one of several microorganisms interacting with the immunocompetent cells of the bowel. Recent studies show that Lactobacillus bulgaricus from yogurt has a strong binding affinity for OKT4+ and OKT8+ cells. This affinity may be comparable to L. casei, which is also endowed with immunomodulating capacities. Cytoadherence occurs in the presence of T cells (both T4+ and T8+ subsets).

Evidence also suggests lactobacilli compete for the same environment with gram-negative bacteria in the intestinal tract (i.e. Escheria coli, Salmonella typhimurium, Clostridium perfringens, Shigella species, and Staphylococcus aureus). Presumably, optimal levels of lactobacilli in the gut would prevent colonization, and hence disease, due to these pathogens.

Therapeutic Approaches

Therapeutically, the ingestion of one billion to ten billion viable L. acidophilus cells daily has been suggested as the optimum level for supplementation. Amounts exceeding this quantity may induce mild gastrointestinal disturbances.

In a study supplementing humans with low fat milk containing viable cultures of L. acidophilus, the total lactobacillus count increased during the period of supplementation and remained there for at least 4 weeks after supplementation was discontinued.

Antibiotic Therapy

Antibiotics can have profound effects on the metabolism of microflora in the gastrointestinal tract, producing changes in bacterial enzymes and metabolic products. The actual microbiological changes related to each type of antibiotic is unpredictable, depending a lot on the drug's antimicrobial activity and route of administration. Hangee-bauer has recommended Lactobacillus supplementation be given following the use of any broad spectrum antibiotic, after (or during) diarrhea and gastroenteritis due to any cause, and whenever repopulation of the intestine with healthy flora is needed to inhibit the multiplication of pathogenic bacteria.

Cancer

In 1977, Bogdanov et.al., were the first to report the potent antitumor activity of L. bulgaricus. The same year, a series of epidemiological studies suggested the consumption of high levels of cultured milk products may reduce the risk of colon cancer. This led to further study on the antitumor effects of L. acidophilus. When fed to mice, milk and colostrum fermented with L. acidophilus DDS1 caused a 16% to 41% reduction in Ehrlich ascites tumor proliferation. Yogurt dialyzate rather than retenate fraction possessed the antitumor principle(s). The anionic fraction of yogurt dialyzate was reported to cause significant inhibition of ascites tumor proliferation in vivo.

Other studies have shown in rats given a normal diet supplemented with L. acidophilus, there was significantly less activity of the following enzymes involved in carcinogenesis: nitroreductase, azo-reductase and beta-glucuronidase. It is interesting then, in humans, unfermented milk with added L. acidophilus resulted in reduced fecal beta-glucosidase and beta-glucuronidase. Nevertheless, it is still premature to determine the relevance of these studies to the clinical setting in cancer therapy.

Escherichia Coli Infection and Traveler's Diarrhea

E. coli is the primary cause of traveler's diarrhea. Rats, pigs and human subjects have significantly lower levels of intestinal E. coli after ingesting low fat milk containing L. acidophilus.

This finding is significant since E. coli has synthesizes the carcinogenic compounds, ethionine and nitrosamine, from nitrates and nitrites. However, in humans, E. coli levels increased to pre-supplementation levels within four weeks of discontinuing L. acidophilus. This suggests L. acidophilus supplementation may be required for long periods if chronic E. coli infection is suspected.

Candida Albicans Vaginal Infections

There is little evidence in support of the popular notion L. acidophilus is of benefit in Candida albicans infections.

In vitro studies, L. acidophilus cultures grown in casitone broth were inoculated with C. albicans. Results were favorable, suggesting L. acidophilus may be effective against yeast infections. However, these in vitro results have not been supported in the clinical setting. In patients where candida spores were found, treatment with L. acidophilus alone offered only temporary relief. Within one week after treatment, the candida microorganisms overgrew the normal flora. When a specific antimycotic drug was added to the L. acidophilus douche, 37 of 38 patients remained free from recurrent candidiasis.

Bifidobacterium adolescentis may inhibit growth of the fungal form of Candida albicans. A product that combines the NCFM strain of L. acidophilus with B. adolescentis has recently appeared on the market and may be effective against yeast infections. However, antibiotics, such as cefazolin and piperacillin should not be taken concomitantly with B. adolescentis.

Chronic Granulomatous Disease

The bactericidal function of leukocytes from people with this disease is impaired. In vitro studies done in 1969, it was reported L. acidophilus restored this function when phagocytized by the leukocytes of a patient with chronic granulomatous disease.

Gynecological Malignancies

Until recently, no effective means existed to prevent the acute side-effects of pelvic radiotherapy treatment in patients with gynecological malignancies. However, there is convincing evidence supplementation with L. acidophilus may be beneficial during these treatments.

Twenty-four patients suffering from gynecological malignancies and scheduled for internal and external irradiation of the pelvic area were selected for a controlled study to test the prevention of intestinal side effects afforded by administration of L. acidophilus. Each day, the test group ingested 150 ml of a fermented milk product containing at least 20 billion live L. acidiophilus bacteria grown on 6.5% lactulose. L. acidophilus was found to prevent radiotherapy-associated diarrhea.

Drug Interactions

Lactobacilli have remarkable growth and metabolic characteristics. However, their activity can be markedly affected by alcohol or antibiotics.

Because antibiotics kill lactobacilli, it seems prudent to take these supplements between antibiotic usage. In the case of sulfa drug therapy, lactobacillus supplementation should be deferred longer until 2-3 hours after the drug is taken.

When taken concurrently, certain drugs may be metabolized by L. acidophilus before they can be absorbed in the stomach or small intestine.

Usually the human stomach and upper intestinal tract are practically free of microorganisms which could degrade the drugs. However, when lactobacilli are taken in the diet or as a therapeutic aid, the metabolism of drugs taken concurrently needs to be considered. Three drugs (sulphasalazine, chloramphenicol palmitate, and phthalylsuphathiazole) and two azo dyes (tartrazine and methyl red) are particularly affected by supplementation with lactobacilli.

Hypercholesterolemia

Considerable evidence from rat and human studies suggests supplementation with L. acidophilus-rich yogurt can reduce serum cholesterol and triglyceride levels within one week. This may be due to the induction of high levels of hydroxymethylglutaryl Coa reductase, a regulatory enzyme in cholesterol synthesis. However, this effect is strain-specific. It was demonstrated, for example, that consumption of the L. acidophilus RP32 strain, also known as the NCFM strain of human origin) significantly inhibited increases in serum cholesterol in pigs fed high-cholesterol diets.

When the same study was done with the pig-derived L. acidophilus P47, no such effect was found. This indicates only certain strains of L. acidophilus act directly on cholesterol in the gastrointestinal tract, and thus may be beneficial in reducing serum cholesterol levels.

Immune Response

Critics have been skeptical of anecdotal reports that bacterial or viral infections resolve quicker following repeated daily L. acidophilus supplementation. However, there is considerable scientific evidence several varieties of lactobacilli, particularly, L. acidophilus, potentiate the immune response to infection by increasing the activity of mononuclear phagocytes and lymphocytes.

Lymphocytes play an important role in human resistance to infections and tumors. L. acidophilus, administered either orally or intraperitoneally, has been shown to improve macrophage function (e.g. colloidal carbon clearance activity, lysosomal enzyme activities and phagocytosis) in mice.

The antitumor activity shown by lactobacilli against experimental and human malignancies is due to stimulation of the immune system.

Intestinal Colonization

L. acidophilus is the most important and stable lactobacilli in the intestine. This strain inhibits the growth of such undesirable microorganisms as Staphylococcus aureus, Salmonella typhimurium, enteropathogenic Escherichia coli and Clostridium perfringens.

It has been demonstrated lactobacillus preparations protect against antibiotic-associated diarrhea. Human studies of oropharyngeal and intestinal microflora colonization with L. acidophilus supplements have shown continuous supplementation is required to maintain continuous high levels of lactobacilli in the intestine.

Lactose Digestion

L. acidophilus (NCFM strain) aids in the treatment of lactose intolerance. The improved digestion of lactose was immediate and did not require daily consumption of milk.

This improvement was not due to hydrolysis (predigestion) of lactose prior to consumption, suggesting the beneficial effects occur in the digestive tract after consumption of milk containing L. acidophilus.

Oral Contraceptive Failure

More than 75 million women are reported to use oral contraceptives employing synthetic or semisynthetic steroids. The oral contraceptive with the lowest failure rate combines estrogen and a progestin, and is taken at a fixed dose on a cyclic regimen. Researchers have found the failure rate for this product is between 0.1 to 5.0 pregnancies per 100 women per year, although more recent studies suggest the rate may be much higher. Concurrent investigations by a number of researchers into this phenomena suggest concurrent use of ampicillin and tetracycline may cause many of these birth-control failures.

One group of researchers found both ampicillin and tetracycline inhibit the bacteria that deconjugate estrogens in the gut for release into the blood stream.

In vitro studies on the effects of these antibiotics, using human and rat liver microsomes, has shown pretreatment with these antibiotics quadruples the rate of aromatic hydroxylation of ethinylestradiol, an estrogen commonly used in birth control pills.

These findings suggest the gut microflora possibly play an important role in the serum levels of estrogens. In order to maintain a balance between the gastrointestinal microflora and to preserve the function of "the pill", supplements of viable L. acidophilus and other lactobacilli should be ingested whenever it is necessary to take estrogen-based oral contraceptives and certain antibiotics in combination.

Urinary Tract Infections

Vaginal and urethral cultures were done on diaphragm users with a history of urinary tract infections. Above normal levels of coliform organisms were detected by the cultures of both sites.

It may be diaphragm usage is associated with changes in the vaginal microflora. L. acidophilus and other lactobacilli have been reported to antagonize E. coli, suggesting these "good" bacteria have a role in the treatment of urinary tract infections.

Vaginal Infections

Normally, L. acidophilus exists in large numbers in the vagina, creating an acidic (pH of 5.0 or lower) environment which inhibits the growth of pathogens and other microorganisms.

Some antimicrobial drugs used for vaginal infections cause side effects and may even inhibit the growth of L. acidophilus and other "good" vaginal bacteria.

A lactobacillus douche can be used in the treatment of vaginal infections, either as a stand-alone therapy or in combination with antimicrobial drugs. Lactobacillus therapy causes no side effects and promotes a recolonization of the vagina with "good" microflora which act as a defense against the infection.

A vaginal douche is prepared using one to ten billion L. acidophilus cells per ml. of liquid media, diluted in 100 ml of a hypertonic solution (1.5-3% NaCl). The douche is used twice daily. In general, stabilization requires one or two weeks of repeated douchings.

A hospital clinical trial has shown this approach produces significant benefit within one week after treatment in approximately 75% of women. 55% of these women showed continued benefit at the 3 to 6-month follow-up.

Some practitioners recommend a vitamin B complex supplement also be taken orally twice a day. When B-complex vitamins were combined with L. acidophilus therapy, follow-up evaluations found 82% of the women had normal microflora and were free from disease.

In all cases, these women had reported prior histories of other treatments for their vaginal complaints, including: erythromycin, ampicillin, tetracycline, canesten and nitrofurazone.

Toxicity Factors

The daily ingestion of one to ten billion viable L. acidophilus cells has been suggested as the optimum level for therapeutics. Amounts exceeding this quantity may induce mild gastrointestinal disturbances.

No reports of allergic reactions to L. acidophilus could be found in the literature. However, a small amount of L. acidophilus should be ingested initially to detect any potential for an allergic reaction, especially if the user has not tried the product before. Lactobacillus nutritional supplements often contain lactose and milk proteins, substances with a high potential for eliciting an allergic response.

References

Aries, V., J.S. Crowther, B.S. Drasar, M.J. Hill & R.E.O. Williams. Bacteria & the etiology of cancer of the large bowel. Gut. 1969. 10;334.

Armstrong, B. & R. Doll. Environmental factors and cancer incidence and mortality in different countries with special reference to dietary practices. Int J Cancer. 1975. 15; 617-631.

Ayebo, A.D. Partial purification of anticarcinogenic compounds of yogurt. Ph.D. Thesis, University of Nebraska-Lincoln, 1980.

Ayebo, A.D., I.A. Angelo, K.M. Shahani & C. Kies. Effect of feeding Lactobacillus acidophilus milk upon fecal flora and enzyme activity in humans. J Dairy Sci. 1979. 62, Supplemental 1; 44.

Bailey, P.J. & K.M. Shahani. Inhibitory effect of acidophilus cultured colostrum and milk upon the proliferation of ascites tumor. Proc 71st Ann Meet Amer Dairy Sci Assoc. 1979. p. 41.

Bareroot, S.F. & T.R. Klaenhammer. Detection and activity of lacticin B, a bacteriocin produced by Lactobacillus acidophilus. Appl Environ Microbio. 1983. 45; 1808-1815.

Burkitt, B.S. Epidemiology of cancer of the colon and rectum. Cancer. 1971. 28; 3-13.

Clements, M.L. et al., Exogenous lactobacilli fed to man-their fate and ability to prevent diarrheal disease. Prog Food Nutr Sci. 1983. 7; 29-37.

Contardi, I: Oral bacteria therapy in prevention of antibiotic-induced diarrhea in childhood. Clin. Ter. 1991, 136(6);409.

Conway, P.L., S.L. Gorbach & B.R. Goldin. Survival of lactic acid bacteria in the human stomach and adhesion to intestinal cells. J Dairy Sci. 1987. 70; 1-12.

Dahiya, R.S. & M.L. Speck. Hydrogen peroxide formation by lactobacilli and its effect on Staphylococcus aureau. J Dairy Sci. 1968. 51; 1568.

De Simone, C. et al., Adherence of specific yogurt micro-organisms to human peripheral blood lymphocytes. Microbios. 1988. 55; 49-57.

Dossetor, J. Drugs interaction with oral contraceptives. BMJ. 1975. 4; 467-468.

Drasar, B.S. & D. Irving. Environmental factors and cancer of the colon and breast. Br J Cancer. 1973. 27; 167-172.

Fredericsson, B et al., Bacterial vaginosis is not a simple ecological disorder. Gyn. Obst. Invest. 1989, 28(3):156.

Friedlander, A et al., Lactobacillus acidophilus and vitamin B complex in the treatment of vaginal infection. Panminerva Med. 1986. 28; 51-53.

Gilliland, SE et al., Influence of consuming nonfermented milk containing Lactobacillus acidophilus on fecal flora of healthy males. J Dairy Sci. 1978. 61; 1-10.

Gilliland, SE et al., Assimiliation of cholesterol by Lactobacillus acidophilus. Appl Environ Microbiol. 1985. 49;377-381.

Goldin, B.R. & S.L. Gorbach. The effect of milk and lactobacillus feeding in human intestinal bacterial enzyme activity. Am J Clin Nutr. 1984. 39; 756-761.

Gorbach, S.L. Function of the normal hunman microflora. Scand J Infect Dis. 1986. Supplemental 49; 17-30.

Gorbach, S.L: Lactic acid bacteria and human health. Ann. Med. 1990, 22(1):37.

Gotz, VP et al., Prophylaxis against ampicillin-induced diarrhea with a lactobacillus preparation. Am J Hosp Pharm. 1979. 36; 754-757.

Hawksworth, G.M. & M.J. Hill. Bacteria and the n-nitrosation on secondary amines. Brit J Cancer. 1971. 25; 520.

Hentges, D.J. ed. Human Intestinal Microflora in Health and Disease. Academic Press. New York. 1983.

Hepner, G et al., Hypocholesterolemic effect of yogurt and milk. Am J Clin Nutr. 1979. 32; 19-25.

Hughes, VL: Microbiologic characteristics of Lactobacillus products used for colonization of the vagina. Obstet. Gynecol. 1990, 75(2);244.

Johnson, MC et al., Selection of Lactobacillus acidophilus strains for use in acidophilus products. Antonie van Leeuwenhoek. 1987. 53; 215-231.

Klebanoff, S.J. & L.R. White. Iodination defect in the leukocytes of a patient with chronic granulomatous disease of childhood. New Eng J Med. 1969. 280; 460-462.

Lauer, E., C. Helming & O. Kandler. Heterogenicity of the species Lactobacillus acidophilus (Moro, Hansen and Moquot) as revealed by biochemical characteristics and DNA-DNA hydridization. Zbl Bakt Hyg 1. Abt Orig C1. 1980. 150-168.

Klaenhammer, T.R. Microbiological considerations in the selection of preparations of lactobacillus strains for use as dietary adjuncts. J Dairy Sci. 1982. 65; 1339-1349.

Klaenhammer, T.R. Bacteriocins of lactic acid bacteria. Biochimie. 1988. 70; 337-349.

Kleeman, E.G. & T.R. Klaenhammer. Adherence of lactobacillus species to human fetal intestinal cells. J Dairy Sci. 1982. 65; 2063-2069.

Lidbeck, A.N., J.A. Gustafsson C.E. Nord. Impact of Lactobacillus acidophilus supplements on the human oropharyngeal and intestinal microflora. Scan J Infect Dis. 1987. 19; 531-537.

Lin, SY: Lactobacillus effects on cholesterol: in vitro and in vivo results. J. Dairy Science, 1989, 72(11):2,885.

Mann, G.V. A factor in yogurt which lowers cholesterolemia in Massai. Am J Clin Nutr. 1974. 27; 464-469.

Marteau, P et al., Effect of chronic ingestion of a fermented dairy product containing Lactobacillus acidophilus and Bifidobacterium bifidum on metabolic activities of the colonic flora in humans. Am. J. Clin. Nutr. 1990, 52(4):685.

Moore, W.E.C. & L.V. Holdeman. Human fecal flora. The normal flora of 20 Japanese-Hawaiians. Appl Microbiol. 1974. 27; 961-979.

Morishita, Y., T. Mitsuoka, C. Kaneuchi, S. Yamamoto M. Ogata. Specific establishment of lactobacilli in the digestive tract of germfree chickens. Japan J Microbiol. 1971. 15; 531.

Muralidhara, K et al., Effect of feeding lactobacilli on coliform and lactobacilli flora of intestinal tissue and feces of piglets. J Food Protect. 1977. 40; 288.

Nair, C.R. & G.V. Mann. A factor in milk which influences cholesterolemia in rats. Atherosclerosis. 1977. 26; 363-368.

Perdigon, G et al., Enhancement of immune response in mice fed with Streptococcus thermophilus and Lactobacillus acidophilus. J Diary Sci. 1987. 70; 919-926.

Perdigon, G et al., Systemic augmentation of the immune response in mice by feeding fermented milks with Lactobacillus casei and Lactobacillus acidophilus. Immunol. 1988. 63; 17-23.

Pradhan, A. & M.K. Majumdar. Metabolism of some drugs by intestinal lactobacilli and their toxicological considerations. Acta Pharmacol Toxicol. 1986. 58; 11-15.

Price, R.J. & J.S. Lee. Inhibition of pseudomonas species by hydrogen peroxide producing lactobacilli. J Milk Food Technol. 1970. 33; 13.

Reid, G et al., Is there a role for lactobacilli in prevention of urogenital and intestinal infections? Clin. Microbiol. Rvw. 1990, 3(4):335.

Reimers, D., L. Nocke-Fink & H. Bever. Rifampicin, "pill" do not go well together. JAMA. 1974. 227; 608.

Schauss, Alexander G. Lactobacillus acidophilus strains as dietary adjuncts - review. Int J Biosocial Med Res. 1989. 11(2); in press.

Shahani, K.M. & A.D. Ayebo. Role of dietary lactobacilli in gastrointestinal microecology. Am J Clin Nutr. 1980. 33; 2488-2457.

Shahani, K.M., J.R. Vakil & A. Kilara. Natural antibiotic activity of Lactobacillus acidophilus and bulgaricus. II. Isolation of acidophilin from L. acidophilus. Cult Dairy Prod J. 1977. 12; 8.

Shahani, K.M. Nutritional impact of lactobacilli fermented foods. XV Symposium of the Swedish Nutrition Foundation. B. Hallgre. ed. Almqvist & Wiksell. Uppsala. 1983. pp. 103-111.

Skinner, F.A. & J.G. Carr. eds. Symposium on the normal microbial flora of man. Applied Bacteriol. 1974. 728(9); 32-57.

Smith, H.W. & W.E. Crabb. The fecal bacterial flora of animals and man, its development in the young. J Pathol Bacteriol. 1961. 82; 53-60.

Swenson, L et al., Effect of antibiotics on fecal urinary excretion of ethinyl estradiol, and oral contraceptive. Gastroenterology. 1980. 78; 1332.

Tikkanan, MJ et al., Effects of antibiotics on oestrogen metabolism. BMJ. 1973. 2; 369.

Vesely, R et al., Influence of a diet additioned with yogurt on the mouse immune system. EOS J Immunol Immunopharmacol. 1985. 5; 30-35.

Vincent, J.G et al., Antibacterial activities associated with Lactobacillus acidophilus. J Bacteriol. 1959. 78; 477.

Weir, D. & C. Blackwell. Interaction of bacteria with the immune system. J Clin Lab Immunol. 1983. 10: 1-12.

Wynder, E. The epidemiology of large bowel cancer. Cancer Res. 1975. 35; 3388-3394.

Wynder, E. & B.S. Reddy. Metabolic epidemiology of colorectal cancer. Cancer. 1974. 34; 801-806.