Natural Antibiotics and Beyond

Lactobacillus Acidophilus

Natural Antibiotics and Beyond

By Debasis Bagchi, Ph.D. and S.K. Dash, Ph.D.

Introduction

1

The human gastrointestinal flora is a complex and finely balanced ecosystem which plays an important role in human health. There are approximately 400 different species of bacteria in the human gastroin-testinal tract (1,2). Lactobacillus acidophilus, Lactobacillus bifidus (also known as Bifidobacterium bifidum) and Streptococcus faecium are major components of healthy intestinal microflora. These mircoflora or beneficial bacteria contribute to the gastrointestinal integrity and maintain the colonization resistance against various diseased conditions and pathogens. It has been extensively demonstrated by researchers that these microflora induce enhanced production of vitamins, enzymes and antimicrobial agents which in turn contribute to good health. Oral administration of these viable bacteria have ceome and important part of supplementation in the prevention and treatment of gastrointestinal dysbiosis.

Lactobacillus acidophilus is found virtually throughout the gastrointestinal tract. The usefulness of L. acidophilus was first identified and demonstrated by Nobel Laureate Metchnikoff (1). O’Sullivan etal. (2) have been referred to L. acidophilus as a probiotic bacteria. The beneficial effects of this probiotic bacteria or microflora include inhibitions of microbial pathogens, alleviation of lactose intolerance, reduction of servum cholesterol levels, induction of anticarcinogenic activity, enhancement of the immune system and improved nutritional value of foods (2-5). Humans are not born with L. acidophilus in the gastrointestinal tract. The colonization of L. acidophilus begins after birth. With environmental exposure some undesirable bacteria are produced in the human body which synthesize toxic amines and in turn induce undesirable or adverse health effects. L. acidophilus is known to produce a natural antibiotic, “acidophilin”, which has been show to possess a wide range of antimicrobial activity against common food-borne pathogens (2). Acidophilin antagonizes the undesirable growth of various bacteria including Bacillus subtilis, Bacillus cereus, Bacillus stearothermophilus, Streptococcus lactic, Lactobacillus lactis, lactobacillus casei, Lactobacillus plantarum, Lactobacillus leichmannii, Sarcina lutea, Serratia marcescens, Proteus vulgaris, Escherichia coli, Clostridium perfringers, Salmonella typhosa, Salmonella schottmuelleri, Shigella dysenteriae, Shigella paradysenteriae, Shigella sonnei, Pseudomonas fluorescens, Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae, and Vibrio coma. L. acidophilus has been reported to produce sufficient hydrogen peroxide to inhibit growth of S. aureus, even at temperature as low as 5 degrees Celsius (2,4). L. acidophilus also inhibits the common yeast Candida albicans and heals acne (2,7). Different strains of L. acidophilus might have specific affinities for different species. It has been suggested that the strain of L. acidophilus used for dietary supplementation should possess the following characteristics if advocated for therapy (8,9):

1. The recommended strain should either be the normal habitant of the host intestine or be capable of adapting to the host gastrointestinal environment.
2. The starin should possess properties that are advantageious to the host gastrointestinal environment.
3. The strains must survive passage into the intestine and be capable of surviving in the small intestine where digestion and absorption of nutrients occur.
4. The strain should not be detrimental to the food, and neither the food should harm the strain.

Mechanistic Pathways of LactobacillusCytoprotection

The following two major mechanistic pathways have been deomonstrated as the salient features of L. acidophilus-induced gastroprotection:

1. L. acidophilus-induced natural antibiotics and hydrogen peroxide produce antimicrobial activity against food and environmental borne pathogens.
2. L. acidophilus enhances immunomodulating factors.

Benefits of Lactobacillus Acidophilus

L. acidophilus has the following demonstrated nutritional and health benefits:

Digest food, alleviate digestive disorders and prevent bad breath: L. acidophilus is the most viable and stable in the

gastrointestinal tract and even it can withstand the gastric pH. It inhibits the growth of Staphulococcus aureus, S. typhimurium, Salmonella typhosa, Clostridium perfringens, Shigella dysenteriae and others. L. acidophilus activity may be affected by alcohol and/or antibiotics. L. acidophilus exhibits a protective effect against gastrointestinal upsets, abdominal pains, constipation, and antibiotic-induced diarrhea (10). During antibiotic treatment a continuous supplementation of L. acidophilus is required to maintain high level of microflora in the gastrointestinal tract (11).

L. acidophilus produces enzymes which help digest food and decrease bloating. In vitro studies have revealed that L. acidophilus has the ability to absorb cooked food mutagens (12). Recent studies in humans have demonstrated that L. acidophilus supplementation significantly reduced the mutagen exretion after consumption of fried meat (12). L. acidophilus has been shown to be useful in treating and preventing various intestinal infections including salmonellosis, shigellosis and antibiotic-induced diarrhea (2, 13, 14). Disruption of this natural microflora ‘L. acidophilus’ of the gastrointestinal tract may occur during antibiotic therapy. This may lead to diarrhea, dehydration, and electrolyte imbalances (14). L. acidophilus treatment has been

shown to prevent Amoxicillin-induced diarrhea (14).

L. acidophilus cultures also have the ability to deconjugate bile salts including sodium taurodeoxycholate in the intestine (15). Colonization of putrefying bacteria in the throat, tongue and mouth causes halitosis (bad breath) (2). Bad breath is caused by the objectionable metabolities produced by dominant putrefying bacteria in the intestine. L. acidophilus inhibits these bacteria and thus helps prevent bad breath. L. acidophilus has been demonstrated to inhibit the growth of Campylobacter pylori or Helicobacter pylori (16), a deadly bacteria responsible for chronic and active gastritis, and various gastrointestinal disorders including gastric cancer.

Enhances syntheses of B-complex vitamins and improves absorption of calcium: L. acidophilus has been demonstrated to induce sythesis of various B-complex vitamins including vitamin B6, B12, folic acid, riboflavin, niacin, biotin and pantothenic acid (17). Furthermore, L. acidophilus supplementation ameliorates altered calcium homeostasis in humans, and improves absorption of calcium (12).

Protect enteropathic Escherichia coli infection: Human intestinal E. coli has been reported to be reduced significantly following administration of L. acidophilus (18). E. coli has been shown to synthesize carcinogenic chemicals including ethionin and nitrosamine; to induce traveler’s diarrhea (19). Without L. acidophilus supplementation, E. coli countshave been shown to increase in humans. L. acidophilus supplementation has been recommended for longer periods in case of chronic E. coli infection (20).

Improve Lactose Tolerance and Improves Digestibility of Milk Products: Deficiency of lactase enzyme causes inefficient digestion of milk-derived lactose, a condition termed as lactose intolerance. L. acidophilus produces lactase enzyme which helps digest lactose (21, 22). Furthermore, irritable bowel syndrome can be prevented following administration of L. acidophilus (23).

Modulates hypercholesterolemia and helps to reduce cholesterol

Supplementation of L. acidophilus in humans can cause a reduction in serum cholesterol and triglyceride levels in one week (24). Specific strains of L. acidophilus have been reported (25) to regulate the levels of hydroxymethylglutaryl CoA reductase (a regulatory enzyme in cholesterol biosynthesis). Certain strains of L. acidophilus act directly on cholesterol in the gastrointestinal tract, and thus may be beneficial in reducing cholesterol levels in humans (26). Gilliland and Walker (27) and Gilliland (28) have suggested that a culture of L. acidophilus of human origin, which assimilates cholesterol, grows well in presence of bile, and produces bacteriocins can be selected for use as a dietary adjunct for humans. A culture of L. acidophilus possessing all these characteristics should have an advantage over one that does not in establishing and fuctioning in the gastrointestinal tract to assimilate cholesterol.

Chawla and Kansal (29) have suggested that inhibition of glucose-6-phosphate dehydrogenaese and/or 6-phosphogluconate dehydrogenase may be one of the reasons for the decrease in cholesterol biosynthesis following regular consumpti9on of L. acidophilus.

Ameliorates Gynecologic Malignancies and Dysfunction

In a clinical study, L. acidophilus has been demonstrated to be a beneficial therapeutic adjunct during pelvic radiotherapy treatment (30). L. acidophilus supplementation has been shown to prevent radiotherapy-associated diarrhea.

Reduces Vaginal Infections and Candidiasis: From puberty to menopause, L. acidophilus exists in large numbers in the vagina and contribute to the maintenance of acid pH through fermentation of carbohydrates (7). L. acidophilus produces a pH of 5.0 of lower causing inhibition of other pathogenic microorganisms (7). When the number of L. acidophilus decrease in the vagina, yeast and other bacteria increase and cause irritation and inflammation. L. acidophilus-derived antimicrobials inhibit the growth of normal saprophytes, while L. acidophilus as such helps to act as a defense against infection (7, 31, 32).

Yeast infections of the vaginal canal (monilia vaginitis) are a distressing and frequently recurring problem for women. Such infections are cuased primarily by Candida albicans and apparently occur when the environmental balance in the vagina is disturbed. Collins and Hardt (7) have demonstrated inhibition of Candida albicans when grown on MRS agar plates (33). The addition of sodium thiocyanate to the agar was found to increase the inihibition offered by the L. acidophilus. The results indicate that hydrogen peroxide produced by L. acidophilus is being used to convert the thiocyanate to hyptothiocyanate which is more toxic. The involvement of Lactobacillus peoxidase in this cytoprotection pathway has been postulated by Jack et al. (33). Hilton et al. (31) have demonstrated that ingestion of yogurt containing L. acidophilus as prophylaxis decreased both candidal colonization and infection, and as well candidal vaginitis in women.

Attenuates Immune Function: L. acidophilus supplementation has been shown to potentiate the immune response to environmental stressors and infection by increasing phagocytic and lymphocytic activity (34, 35) and antagonizing pathogenic bacteria. Oral and intraperitoneal administration of this unique bacterial culture improves the activity of lymphocytes and several macrophage functions including phagocytosis, lysosomal enzyme activities, and colloidal carbon clearance activity (34, 35).. These are useful in increasing resistance to infections and tumor promotion (34-36).

Holgado etal. (37) have reported L. acidophilus as a clinical immunopotentiator. They have shown increased B-galactosidase activity of peritoneal macrophages in invivo model, while increased phagocytic activity in the invitro model. Clearance of colloidal carbon from blood, increased level of circulating antibodies and activation of immune system were also demonstrated. L. acidophilus has also been shown to significantly increase the activities of B-galactosidase, B-glucuronidase, lactate deyhdrogenase and phagocytes following oral or intraperitoneal administration (38). Furthermore, the phagocytic function of the reticuloendothelial system, determined by carbon clearance test, was markedly stimulated by this unique microflora. L. acidophilus-induced increased lymphocyte activity was also estimated using IgM-secreting sheep erythrocytes (38).

The colonization of Salmonella typhimurium in the liver and spleen tissues can be markedly inhibited by supplementation of L. acidophilus and L. casei (39). The highest levels of anti-Salmonella antibodies in serum and intestinal fluid were determined in in vivo model following oral treatment with L. acidophilus and L. casei (39). The study further suggested that the augmentation of resistance to Salmonella caused by the treatment of Lactobacillus acidophilus and Lactobacillus casei was due to the anti-Salmonella protective immunity mainly mediated by the gastric mucosal tissue (39).

In a recent paper, Perdigon et al (40) have evaluated the effects of lactic acid bacteria on the system immune response and on the secretory immune system and defined these selected bacteria as immunomodulatory agents. Potential health benefits of lactic acid bacteria, as described by Perdigon et al. (40), include protection against enteric infections, use as an oral adjuvant, the immunopotentiator in malnutrition, and the prevention of chemically induced tumors (40). L. casei has been shown to stimulate enhanced synthesis of IgA and IgM in malnourished animals. It can further inhibit the growth of intestinal carcinoma through increased activity of IgA, T cells, and macrophages (40).

Prevents Chronic Granulomatous Disease: L. acidophilus has been reported to restore genetically impaired bactericidal function of the leukocytes associated with chronic granulomatous disease (41).

Antitumorogenic/ Anticarcinogenic Activity:

In human studies, L. acidophlus ingestion resulted in reduced fecal B-glucosidase and B-glucuronidase; enzymes that increase the converstion rate of procarcinogens to proximal carcinogens (20). L. acidophilus has been reported to result in a 16% to 41% reduction in proliferation of Ehrlich ascites neoplasm (27,42,43). L. acidophilus has been shown to reduce the activites of other enzymes including nitroreductase, which are involved in chemical carcinogenesis (44). In a clinical study conducted by Lidbeck et al (12, 45), colon cancer patients were given L. acidophilus supplementation and significant increases both in the number of intestinal microflora and dietary calcium intake were observed. Furthermore, decreasing trands in levels of both soluble faecal bile acids and faecal bacterial enzymes, two biochemical risk markers for colon cancer, were observed. Several mechanisms and metabolic activities by which this novel microflora might exert anticarcinogens activities have been extensively demonstrated (12, 45, 46). The antagonistic action of L. acidophilus towards intestinal and food borne pathogens has been extensively demonstrated by several leading researchers in the field, and definitely implies the protective abilities of this microflora in potentiating antitumorogenic /anticarcinogenic activity and maintaining the gastrointestinal ecology (47).

Prebiotics for Acidophilus and Bifidus

Fructooligosaccharides (FOS) are naturally occurring compounds found in a wide variety of edible plants such as banana, barley, garlic, honey, onion, wheat, tomato, rye, and brown sugar. These compounds are selectively are selectively utilized by the beneficial intestinal microflora for growth and proliferation. Conversely, pathogenic bacteria including Escherichia coli, Clostridium perfringers and others have been shown to be unable to utilize these FOS, which are nontoxic and free of side effects (48). FOS promotes, stabilizes and enhances the proliferation of these beneficial gastrointestinal microflora (48). Thus, incorporation of FOS in the diet or supplement will intensify the viability and adhesion of L. acidophilus in the gastrointestinal tract (48).

Selection of Acidophilus Strain

Since all L. acidophilus strains are not the same and do not have the same nutritional, antimicrobial and other therapeutic properties, it is important to select the correct strain of L. acidophilus. It should be well researched and shown to possess most nutritional, antimicrobial and other therapeutic properties. One such strain is DDS-L. acidophilus manufactured and marketed by AUS Laboratories of Minnetonka, MN. Freeze drying, nitrogen flushing and refrigeration of the product enhance the stability and keeping quality of L. acidophilus. On the other hand most of L. acidophilus product sitting on the shelf without refrigeration, have hardly and viable culture. L. acidophilus in liquid form is not viable for a longer period of time. Powder form of L. acidophilus has more surface area and hence more prone to contamination and oxidation. For this reason, L. acidophilus in capsule and tablet forms are highly recommended.

Non-dairy L. acidophilus products are very popular and recommended by health professional. Persons who are allergic to milk and dairy products want non-dairy L. acidophilus and doctors find non-dairy L. acidophilus more effective for Candidiasis patients (49). Since 70-80% females and 30-40% males have some degree of yeast infection, and many are allergic to milk and dairy products, non-dairy L. acidophilus products are getting wide acceptance among consumers.

Benefits associated with one particular strain of L. acidophilus may not necessarily apply to other strains of L. acidophilus. Furthermore, sophisticated processing, packaging, and storing are warranted to maintain the viability and integrity of L. acidophilus.

Clinical Reports

An independent study was conducted by Dr. Keth W. Sehnert, a well-reputed alternative health care practitioner in Minneapolis, in collaboration with AugsburgCollege in Minneapolis during 1987-1989. A total of seventy participants participated in this study to determine the beneficial effects of L. acidophilus (manufactured by: UAS Laboratories, Minnetonka, MN) on traveler’s diarrhea. The participants received two Acidophilus capsules per day for a week prior to the trip and during their trip to Nepal, Mexico, and Guatemala. Only two of the seventy participants experienced any digestive disorders (49). The usual incidence of traveler’s diarrhea is about 20-30% (49).

Studies conducted by Dr. Sehnert further showed that digestive disorders including diarrhea, travelers trots, constipation, irritable colon and colitis can be relieved by the administration of proper Acidophilus products (49). In a separate study, Dr. Sehnert provided the Acidophilus capsules (manufactured by: UAS Laboratories, Minnetonka, MN) product to 42 patients at a primary care clinic. The responses reported in the patient response cards are summarized below (49):

D

Another study was conducted by Dr. Lance R. Peterson, MD, Chief, Infectious Diseases Section of The Veteran’s Administration Medical Center, MN, who demonstrated the persistence and likely replication of this microflora in the gastrointestinal tract of several patients (50). Furthermore, the number of lactobacilli increased more than one-hundred fold in the patients following a conducted therapy with Acidophilus capsules (manufactured by: UAS Laboratories, Minnetonka, MN) (50).

Studies by Harvard Researcher at BostonCityHospital with alcoholics who had severe liver problems showed their mental confusion and clinical status significantly improved following the use of lactobacilli. The improvement was attributed to suppression of the aerobic bacterial flora by L. acidophilus (51).

Conclusion

Research clearly demonstrates the positive role of L. acidophilus in maintaining the gastrointestinal ecology. As the environmental toxins, antibiotics and other medications, processed food, polluted and contaminated water, pesticides etc. constantly damage the intestinal microflora and reduce the number of beneficial L. acidophilus, it is imperative to supplement the daily diet with the correct strain of L. acidophilus. One to two billion colony forming units (CFU) of L. acidophilus is usually recommended for maintenance of beneficial gastrointestinal microflora. Commerical yogurt sitting on the store shelf does not have many viable beneficial bacteria. On the other hand, home-made yogurt does not provide the needed amount of L. acdophilus. For this reason, supplementation of L. acidophilus is in capsule and tablet forms are highly recommended.