The Probiotic Effects of Lactic Acid Bacteria

Lactic acid bacteria have a number of well-established benefits.

Summary

Probiotics are defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host.” One of the most significant groups of probiotic organisms are the lactic acid bacteria, commonly used in fermented dairy products. These bacteria have a long history of safe use in food. There is an upsurge in interest in these species as research is beginning to reveal the many possible health benefits associated with lactic acid bacteria.

The actions of lactic acid bacteria are species and strain specific, and depend on sufficient numbers of bacteria being available in the intestines. The difficulty in identifying and classifying strains has complicated research, since benefits may only pertain to particular strains.

Nevertheless, lactic acid bacteria have a number of well-established benefits. They can improve lactose digestion, play a role in preventing and treating diarrhea and act on the immune system, helping the body to resist and fight infection.

More work needs to be done to confirm the role lactic acid bacteria might play in preventing or slowing the growth of colon cancer, lowering cholesterol levels, preventing urogenital infections, alleviating constipation and treating food allergy.

Probiotics…a special case

In the quest for discovering how food can enhance health or prevent chronic diseases, researchers have stumbled on to another range of components in foods besides nutrients. This growing area of information has resulted in a new label for foods that have added benefits: functional foods.

Functional foods contain significant levels of biologically active components that provide health benefits beyond basic nutrition. Other terms for functional foods include nutraceuticals, pharmafoods, designer foods, mood foods…Some examples of functional foods are:

• oats and barley, which contain beta-glucans, and can improve blood sugar control and reduce blood cholesterol.
• cooked tomatoes, which contain the phytochemical lycopene, and may reduce risk of prostate and cervical cancer.
• yogurt and other cultured milk products, which contain lactic acid bacteria, and can enhance gastrointestinal system function. In fact, the potential benefits of yogurt and other foods containing living organisms are so numerous that they form a special sub-group of functional foods: probiotic foods.

The probiotic effects of lactic acid bacteria

Long before the term ‘probiotic’ was coined, Elie Metchnikoff, the Nobel laureate immunologist, suggested in 1908 that the reason Balkan peasants lived long lives was because they drank milk fermented with Lactobacillus bulgaricus and Streptococcus thermophilus (1). He suggested that these bacteria would suppress “putrefactive fermentation”, leading to better health and longevity. His ideas generated great interest in the role gut microflora play in health, an interest that persists to this day.

Today, many potential health benefits of probiotic bacteria are under investigation, from improving the microbial balance in the intestine to enhancing immune system function.

Probiotics are defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host” (2). One of the most significant groups of probiotic organisms are the lactic acid bacteria.

What are lactic acid bacteria?

Lactic acid bacteria produce lactic acid as their main product. They are widespread in nature—in soil, vegetables, meat, milk and the human body. Many are used in fermented dairy products. Streptococcus thermophilus (S. thermophilus) and Lactobacillus bulgaricus (L. bulgaricus) are the two bacteria required to make yogurt. Many commercial yogurts in Canada also contain Lactobacillus acidophilus (L. acidophilus) and Bifidobacterium bifidus (B. bifidus). Lactobacillus casei (L. casei) is frequently found in cheeses. All these species of bacteria are accepted by Canada as probiotic (3).

These species can be further classified into subspecies, variants and strains. The difficulty in identifying and classifying strains has complicated research, since benefits may only pertain to particular strains.

The evolution of a name…

Lactobacillus GG (LGG) initially was classified as L. acidophilus strain GG, named after the discoverers Gorbach and Goldin. It evolved to being named L. casei subspecies rhamnosum, or L. rhamnosum. More recently it has been proposed that it be reclassified as a unique species: L. zeae. It is still commonly called Lactobacillus GG.

Thus, research conducted when LGG was classified as L. acidophilus would have attributed any benefits to acidophilus. This would no longer be the case.

What makes a bacteria probiotic?

For bacteria to exert any probiotic effect, they have to be able to survive both the stomach acids (pH as low as 1.5) and the bile acids (pH as low as 2). This is true of most lactobacilli.

Secondly, the bacteria must arrive in the intestines in sufficient quantities to have an effect. The amount required depends on the strain and the health benefit being studied. The minimum effective level for individual bacteria and specific health benefits is actively under research.

The bacteria may need to adhere to the wall of the intestine (i.e. “implant”) and colonize in order for there to be an effect. Sherwood Gorbach, one of the discoverers of Lactobacillus GG, states, “Our research over the previous 20 years had established beyond doubt that implantation in the gut was the critical feature that a strain must possess to influence the intestinal milieu…” (4). However, others contend that continuous transit (e.g. continually eating a probiotic food) is an alternative to the organism implanting and colonizing (5).

Finally, the bacteria must show some beneficial effects on human health. Some examples of beneficial effects under investigation include alleviation of lactose intolerance, prevention and treatment of diarrhea, maintenance of normal intestinal flora, antagonism against pathogens, stimulation of the immune system, anticarcinogenic activity, and reduction of serum cholesterol levels.

Effects of probiotics: what’s the evidence?

Established benefits

Lactose digestion

It is well-known that the presence of lactic acid bacteria, specifically L bulgaricus and S thermophilus in yogurt, improves lactose digestion (6). It appears that the cell walls of the bacteria have to be intact (as is the case when the bacteria are alive) for the effect to occur (7). Some possible mechanisms for the improved lactose digestion include:

• The lactase activity of the bacteria actually does the work of digesting lactose in the product once it reaches the intestine (8).
• The slower transit time of yogurt may permit more time for the residual intestinal lactase and the yogurt bacteria to digest the lactose (9).
• Something in the yogurt may inhibit fermentation of lactose and thus reduce symptoms (9).

Sweet acidophilus milk (milk with L. acidophilus which has not been allowed to ferment) does not seem to alleviate the symptoms of lactose maldigestion. Although some work shows a small effect, most work shows no effect (10).

Diarrhea

Lactic acid bacteria may be useful in preventing and shortening the duration of several types of diarrhea (11).

A number of well-designed studies have noted that fermented milk products effectively prevent or treat infantile diarrhea (12). Effects have been noted with L. casei and B. bifidum.

A few small studies show that lactic acid bacteria can reduce the incidence of antibiotic-related diarrhea (13). This suggests a role for lactic acid bacteria in immunosuppressed patients who routinely use antibiotics (14).

A few studies of traveller’s diarrhea have demonstrated the effectiveness of lactic acid bacteria in decreasing the incidence of diarrhea (15, 16).

Lactic acid bacteria can probably reduce diarrhea in several ways:

• Lactic acid bacteria compete with pathogens for nutrients and space in the intestines (13).
• By-products of metabolism may have a direct effect against the pathogens. For example, in vitro work shows that L. casei, L. acidophilus and L. bulgaricus can all produce antimicrobial agents such as acidophilin and bulgarican that can inhibit growth of pathogens (13).
• Lactic acid bacteria may be effective against diarrhea due to effects on the immune system.

Effects on the immune system

Lactic acid bacteria enhance immune system function at the intestinal and systemic levels. In humans, lactic acid bacteria have been shown to increase:

• B-lymphocytes or B cells, which recognize foreign matter (17),
• phagocytic activity, helping to destroy foreign matter (18),
• IgA-, IgG- and IgM-secreting cells and serum IgA levels, which would increase antibody activity (19), and
• γ-interferon levels, which help white blood cells fight disease (20).

Another way the body’s defenses work is by the barrier provided by the mucus layers of the intestine. The mucosa provides a physical barrier, usually preventing foreign substances from passing through the gut. As well, a large variety of immune cells are found in the gut mucosa. This allows the gut to interact with the immune system. Lactic acid bacteria can stimulate immune activity in the intestinal mucosa (21).

In conditions such as allergy or auto-brewery syndrome (abnormal gut fermentation resulting in increased levels of blood ethanol), the permeability of the small intestine can increase, allowing undigested protein molecules to pass through (22). Lactobacillus GG has been shown to reverse gut permeability (23).

Probiotic bacteria may be able to play a role in treating food allergy. This was demonstrated in an experiment with infants known to have excema due to a cow milk allergy (24). Infants in the experimental group got hydrolyzed whey formula fortified with LGG, while those in the control group just got whey formula. The skin condition of the infants getting the LGG improved significantly compared to the control group. In addition, the experimental group had improved levels of factors associated with inflammation of the intestine.

Potential benefits

Hypocholesterolemic effects

Some strains of L. acidophilus can take up cholesterol in the presence of bile (25). Other in vitro research shows that cholesterol can precipitate with free bile salts in the presence ofL. acidophilus, especially in an acid environment (26). Thus, it has been hypothesized that one or both of these actions would take place in vivo and help lower serum cholesterol in humans.

Various studies with fermented milk products have shown either no effect or a reduction in cholesterol levels. In conclusion, there is not yet good evidence to confirm a cholesterol-lowering effect of fermented milk products.

Constipation

Milk products fermented with some strains of L. acidophilus and bifidobacteria shorten intestinal transit time. This effect may be useful for those with constipation, such as the elderly (27). A well-controlled human study is needed to confirm this.

Colon cancer

Several lactic acid bacteria may help prevent initiation of colon cancer. It has also been demonstrated that lactic acid bacteria slow the growth of experimental cancers, although the results are not long-term.

It appears that lactic acid bacteria can reduce the levels of colon enzymes that convert procarcinogens to carcinogens. Specifically, lactic acid bacteria can reduce levels of the enzymes β-glucuronidase, nitroreductase, and azoreductase (28). Lactic acid bacteria may also be involved in the direct reduction of procarcinogens, for example, by taking up nitrites and by reducing the levels of secondary bile salts (28). In most reports, these effects only occur during the period of time that the bacteria are consumed (28).

Changes in enzyme activity in humans have been observed with L. acidophilus and B. bifidum (29), and LGG (30). Animal studies show fewer tumors in those exposed to a carcinogen, in the presence of LGG, compared to the animals exposed to the carcinogen without the benefit of LGG (31). In humans, epidemiological reports show that populations eating fermented dairy products have a decreased risk of colon cancer (32). However, there is not yet a clear relationship between lactic acid bacteria intake and cancer prevention.

Urogenital infections

Lactic acid bacteria may reduce candidal vaginal infections.This is still speculative,however it would be research worth pursuing. One small study showed that women with recurrent vaginal candidiasis who ate 8 oz. daily of a yogurt containing L acidophilus had fewer occurrences of vaginal candidiasis than during the control period in which they ate no yogurt (33). This was a cross-over study which started with 21 women. Eight of those who started in the treatment group refused to cross over to the control phase since they experienced so many fewer infections.Thus only 13 women completed the study.

Ulcers

Lactic acid bacteria show some promise against stomach ulcers. Work with a specific strain of L. acidophilus demonstrated that L. acidophilus competes effectively (in vitro ) against Heliobacter pylori for attachment sites, limiting the number of H. pylori that can attach to the cell wall (34). Infection with H. pylori is a risk factor for stomach ulcers. A small study of patients with ulcers showed that Bifidobacteria bifidum promoted healing of gastric ulcers in 50% of the patients and eradication of H. pylori from the mucous membranes in 30% of the patients (35).

Some probiotic foods: which bacteria do they contain?

Yogurt always contains L. bulgaricus and S. thermophilus, and may contain L. acidophilus and bifidobacteria.

Acidophilus milk contains Lactobacillus acidophilus.

Kefir contains numerous lactic acid bacteria, including Lactococcus lactis, Lactococcus cremoris, Lactobacillus kefir, Lactobacillus casei, Lactobacillus acidophilus and Leuconostoc species. It also contains yeasts.

It is important to remember that probiotic benefits require a minimum number of bacteria to achieve benefits. Although minimum levels are not yet established, research doses are typically on the order of 1 billion cells. Not all fermented products will contain enough active microorganisms. The fresher the product, the more organisms will be active.

Safety of probiotics

Lactic acid bacteria traditionally used in fermented dairy products have a long history of safe use. However, as interest grows in using new strains, safety testing will become important.

Lactobacillus GG has undergone extensive testing for the safety and efficacy of its use. It was approved in 1992 by the United Kingdom Advisory Committee on Novel Foods and in 1996 by the Japanese functional food authorities (36).

In Canada, probiotics are considered a food ingredient when added to food and are regulated by Health Canada under the Food and Drug Act. The Canadian Food Inspection Agency (CFIA) is responsible for enforcing the Food and Drug Act, while manufacturers are  responsible for the safety of foods they produce and sell. Health Canada has produced a guidance document outlining how health claims about probiotics can be made (37).

References

1. Metchnikoff E. 1908. The Prolongation of Life, 1st edition. G.P. Putnam’s Sons, NY.
2. Hill C. et al. 2014. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and approproiate use of the term probiotic. Nature Reviews Gastroenterology & Hepatology 11:506–514.  doi:10.1038/nrgastro.2014.66
3. Health Canada. 2009. Accepted claims about the nature of probiotic microorganisms in food. http://www.hc-sc.gc.ca/fn-an/label-etiquet/claims-reclam/probiotics_claims-allegations_probiotiques-eng.php
4. Gorbach S.L. 1996. The Discovery of Lactobacillus GG. Nutrition Today Vol. 31(6) (suppl.):2S–4S.
5. Saloff-Coste C.J. 1997. Lactobacillus acidophilus. Danone World Newsletter No. 13.
6. Martini M.C., D. Kukielka, D. Savaiano. 1991. Lactose digestion from yogurt: influence of a meal and additional lactose. Am. J. Clin. Nutr. 53:1253–8.
7. Kuhn C., A. Titze, C.A. Lorenz. 1996. Are viable microorganisms essential for the enhancement of intestinal hydrolysis of lactose by the β-galactosidase of fermented milk products? IDF Nutrition Newsletter 5:38.
8. Martini M.C., G.L. Bollweg, M.D. Levitt, et al. 1987. Lactose digestion by yogurt β-galactosidase: influence of pH and microbial cell integrity. Am. J. Clin. Nutr. 45:432–436.
9. Schaafsma G. 1993. Lactose intolerance and consumption of cultured dairy products — a review. IDF Nutrition Newsletter 2:15–16. 9. Onwulata C.I., D.R. Rao, P. Vankineni. 1989.
10. Relative efficiency of yogurt, sweet acidophilus milk, hydrolyzed-lactose milk, and a commercial lactase tablet in alleviating lactose maldigestion. Am. J. Clin. Nutr. 49:1233–1237.
11. Sanders M.E. 1994. Lactic acid bacteria as promoters of human health. In Functional Foods, ed. I. Goldberg. London: Chapman & Hall. 294–322.
12. Saloff-Coste C.J. 1995. Diarrhea and fermented milks. Danone World Newsletter No. 8.
13. Salminen S., M. Deighton. 1992. Lactic acid bacteria in the gut in normal and disordered states. Dig. Dis. 10:227–38.
14. Aronsson B., P. Barany, C.E. Nord, et al. 1987. Clostridium difficile-associated diarrhea in uremic patients. Eur. J. Clin. Microbiol. 6:352–356.
15. Black F.T., P.L. Andersen, J. Orskov, et al. 1989. Prophylactic efficacy of lactobacilli on traveller’s diarrhea. Travel. Med. 7:333–335.
16. Oksanen P.J., S. Salminen, M. Saxelin, et al. 1990. Prevention of traveller’s diarrhea by Lactobacillus GG. Ann. Med. 22:53–56.
17. De Simone C., R. Vesely, B. Bianchi Salvadori, et al. 1993. The role of probiotics in modulation of the immune system in man and in animals. Int. J. Immunother. IX:23–28.
18. Schiffrin E.J., F. Rochat, H. Link-Amster, et al. 1995. Immunomodulation of human blood cells following the ingestion of lactic acid bacteria. J. of Dairy Science 78:491–497.
19. Kaila M., E. Isolauri, E. Soppi, et al. 1992. Enhancement of the circulating antibody secreting cell response on human diarrhea by a human lactobacillus strain. Pediatr. Res. 32:141–144.
20. Halpern G.M., K.G. Vruwink, J. Van de Water, et al. 1991. Influence of long-term yoghurt consumption in young adults. Int. J. Immunother. VII:205–210.
21. Perdigón G., M. Medici, M.E. Bibas Bonet de Jorat, et al. 1993. Immunomodulating effects of lactic acid bacteria on mucosal and tumoral immunity. Int. J. Immunother. IX:29–52.
22. Joneja J.M., E.A. Ayre, K. Paterson. 1997. Abnormal gut fermentation: the “auto-brewery” syndrome. J. Can. Diet. Assoc. 58(2):97–99.
23. Isolauri E., H. Majamaa, T. Arvola, et al. 1993. Lactobacillus casei strain GG reverses increased intestinal permeability induced by cows milk in suckling rats. Gastroenterology 105:643–1650.
24. Majamaa, H., E. Isolauri. 1997. Probiotics: A novel approach in the management of food allergy. J. Allergy and Clin. Immunol. Feb:179–185.
25. Buck L.M., S.E. Gilliland. 1994. Comparison of freshly isolated strains of Lactobacillus acidophilus of human intestinal origin for ability to assimilate cholesterol during growth. Journal of Dairy Science 77:2925–2933.
26. Klaver F.A.M., R. van der Meer. 1993. The assumed assimilation of cholesterol by lactobacilli and Bifidobacterium bifidum is due to their bile salt-deconjugating activity. Appl. Environ. Microbiol. 59:1120–1124.
27. Hitchins A.D., F.E. McDonough. 1989. Prophylactic and therapeutic aspects of fermented milk. Am. J. of Clin. Nutr. 49:675–684.
28. Fernandes C.F., K.M. Shahani. 1990. Anticarcinogenic and immunological properties of dietary lactobacilli. Journal of Food Protection 53:704–710.
29. Marteau P., P. Pochart, B. Flourié, et al. 1990. 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. 52:685–688.
30. Goldin B.R., S.L. Gorbach. 1984. The effect of milk and lactobacillus feeding on human intestinal bacterial enzyme activity. Am. J. Clin. Nutr. 39:756–61.
31. Goldin B. 1996. The metabolic activity of the intestinal microflora and its role in colon cancer. Nutrition Today 31(6)(suppl):24S–27S.
32. Kampman E., R.A. Goldbohm, P.A. van den Brandt, et al. 1994. Fermented dairy products, calcium and colorectal cancer in the Netherlands cohort study. Cancer Research 54:3186–3190.
33. Hilton E., H.D. Isenberg, P. Alperstein, et al. 1992. Ingestion of yogurt containing Lactobacillus acidophilus as prophylaxis for candidal vaginitis. Ann. Int. Medicine. 116:353–57.
34. Brassart D., A. Donnet-Hughes, J.-R. Neeser, et al. 1995. Dairy bacterial strains with probiotic properties: criteria for selection. IDF Nutrition Newsletter 4:29–32.
35. Salminen S., R. Tanaka. 1995. Annual review on cultured milks and probiotics. IDF Nutrition Newsletter 4:47–50.
36. Seppo J., D.C. Donohue. 1996. Safety assessment of Lactobacillus strain GG (ATCC 53103). Nutrition Today 31(6)(suppl.):12S–15S.
37. Health Canada. 2009. The Use of Probiotic Microorganisms in Food. http://www.hc-sc.gc.ca/fn-an/legislation/guide-ld/probiotics_guidance-orientation_probiotiques-eng.php