Beruflich Dokumente
Kultur Dokumente
doi: 10.1111/j.1740-0929.2009.00645.x
REVIEW ARTICLE
Health-beneficial effects of probiotics: Its mode
of action
asj_645
361..371
Department of Food Science and Technology, Nippon Veterinary and Life Science University, Musashino, Tokyo,
and 2Kyoto Prefectural University, Shimogamo, Kyoto, Japan
ABSTRACT
It is now widely recognized that probiotics have health-beneficial effects on humans and animals. Probiotics should survive
in the intestinal tract to exert beneficial effects on the hosts health. To keep a sufficient level of probiotic bacteria in the
gastrointestinal tract, a shorter interval between doses may be required. Although adherence to the intestinal epithelial cell
and mucus is not a universal property of probiotics, high ability to adhere to the intestinal surface might strongly interfere
with infection of pathogenic bacteria and regulate the immune system. The administration of probiotic Lactobacillus
stimulated indigenous Lactobacilli and the production of short-chain fatty acids. This alteration of the intestinal
environment should contribute to maintain the hosts health. The immunomodulatory effects of probiotics are related to
important parts of their beneficial effects. Probiotics may modulate the intestinal immune response through the stimulation
of certain cytokine and IgA secretion in intestinal mucosa. The health-beneficial effects, in particular the
immunomodulation effect, of probiotics depend on the strain used. Differences in indigenous intestinal microflora
significantly alter the magnitude of the effects of a probiotic. Specific probiotic strains suitable for each animal species and
their life stage as well as each individual should be found.
Key words: intestinal microflora, lactic acid bacteria, probiotics, short-chain fatty acid.
INTRODUCTION
Live bacterial supplements are widely used for the
promotion and improvement of health in humans and
animals. Such supplements are defined as probiotics
(Fuller 1989). Probiotics provide beneficial effects on
the hosts health by affecting the intestinal microflora.
Their beneficial effects on human health, such as the
alleviation of lactose intolerance, immunomodulation,
decrease in fecal enzymes and mutagenicity, hypocholesterolemic effect, and reduction of the risk of gastrointestinal disease have been demonstrated in many
studies (Macfarlane & Cummings 1999; Roberfroid
2000; Dunne 2001; Marteau et al. 2001; Isolauri et al.
2004; Ljungh & Wadstrm 2005; Delcenserie et al.
2008). In the case of humans, lactose intolerance is
one of the typical osmotic diarrheas often manifest in
the subjects with a low intestinal b-galactosidase activity (Heyman 2000). Probiotics have been shown to
Adherence inhibition
Growth inhibition
Growth stimulation
Pathogens
Harmful Bacteria
Adherence inhibition
Growth inhibition
Probiotic Lactobacillus
Lactate
Lactate utilizing bacteria
Short-chain fatty acids
Preventive and
therapeutic effect
Decreasing in luminal pH
Stimulation of epithelial cell growth
Stimulation of colonic blood flow
Modification of intestinal motility
Absorption of water and minerals
Increasing in mucus production
etc.
363
PROBIOTICS
As described above, indigenous intestinal bacteria beneficially affect host health. In general, Lactobacillus and
Bifidobacterium are not pathogenetic and are usually
considered to be health-promoting bacteria (Fuller &
Gibson 1997; Mitsuoka 2000). Therefore, the stimulation of these health-promoting bacteria may improve
Lactobacillus
Bifidobacterium
Enterococcus
Bacillus
Pediococcus
Saccharomycecs
Aspergillus
Escherichia
acidophilus
casei
plantarum
delbruekii subsp. bulgaricus
reuteri
gasseri
fermentum
salivarius
bifidum
lactis
faecium
subtilis
cereus
coagulans
licheniformis
pentosaceus
cerevisiae
boulardii
oryzae
coli
365
367
CONCLUSION
Probiotic bacteria, according to their definition, must
be prepared in a viable form. They should be stable
during preparation and storage, and of course, they
should survive in the intestinal tract to have beneficial
effects on the hosts health. To retain a high level of
probiotic bacteria in the gastrointestinal tract, a shorter
interval between doses may be required. Although
adherence to intestinal epithelial cells and mucus is
not a universal property of probiotics, a high ability to
adhere to the intestinal surface might strongly interfere with infection by pathogenic bacteria and regulate
the immune system. The health-beneficial effects, in
particular the immunomodulate effect of probiotics,
depend on the strain.
Some of the health-beneficial effects are directly
provided by the administered probiotics. However,
many of them are apparently mediated by indigenous bacteria through the activation of fermentation and the recovery of the equilibrium of the
microflora in the pathogenic condition or after antibiotic therapy.
REFERENCES
Allison MJ, Robinson IM, Bucklin JA, Booth GD. 1979. Comparison of bacterial populations of the pig cecum and colon
based upon enumeration with specific energy sources.
Applied and Environmental Microbiology 37, 11421151.
Bassotti G, Crowell M, Whitrhead WE. 1993. Contractile
activity of the human colon: lessons from 24 hour studies.
Gut 34, 129133.
Belenguer A, Duncan SH, Calder AG, Holtrop G, Louis P,
Lobley GE, Flint HJ. 2006. Two routes of metabolic crossfeeding between Bifidobacterium adolescentis and butyrateproducing anaerobes from the human gut. Applied and
Environmental Microbiology 72, 35933599.
Bernet MF, Brassart D, Neeser JR, Servin AL. 1994. Lactobacillus acidophilus LA1 binds to cultured human intestinal
cell lines and inhibits cell attachment and cell invasion by
enterovirulent bacteria. Gut 35, 483489.
Bezkorovainy A. 2001. Probiotics: determinants of survival
and growth in the gut. American Journal of Clinical Nutrition
73 (Suppl), 399S405S.
Bouhnik Y, Pochart P, Marteau P, Arlet G, Goderel I,
Rambaud JC. 1992. Fecal recovery in humans of viable
Bifidobacterium sp. ingested in fermented milk. Gastroenterology 102, 875878.
Bourriaud C, Robins RJ, Martin L, Kozlowski F, Tenailleau E,
Cherbut C, Michel C. 2005. Lactate is mainly fermented
to butyrate by human intestinal microfloras but interindividual variation is evident. Journal of Applied Microbiology 99, 201212.
Butler JE, Sun J, Weber P, Navarro P, Francis D. 2000.
Antibody repertoire development in fetal and newborn
piglets, III. Colonization of the gastrointestinal tract selectively diversifies the preimmune repertoire in mucosal
lymphoid tissue. Immunology 100, 119130.
Canibe N, Jensen BB. 2003. Fermented and nonfermented
liquid feed to growing pigs: effect on aspects of gastrointestinal ecology and growth performance. Journal of
Animal Science 81, 20192031.
Carol M, Borruel N, Antolin M, Llopis M, Casellas F, Guarner
F, Malagelada JR. 2006. Modulation of apoptosis in intestinal lymphocytes by a probiotic bacteria in Crohns
disease. Journal of Leukocyte Biology 79, 917922.
Carson CF, Riley TV. 2003. Non-antibiotic therapies for
infectious diseases. Communicable Diseases Intelligence 27
(Suppl), S143146.
Cebra JJ, Priwal SB, Lee G, Lee F, Shroff KE. 1998. Development and maintenance of the gut-associated lymphoid
tissue (GALT): the roles of enteric bacteria and viruses.
Developmental Immunology 6, 1318.
Chadwick VS, Anderson RP. 1995. Role of intestinal bacteria
in etiology and maintenance of inflammatory bowel
disease. In: Gibson GR, Macfarlane GT (eds), Human
Colonic Bacteria: Role in Nutrition, Physiology And Pathology,
pp. 227256. CRC Press, London.
Charteris WP, Kelly PM, Morelli L, Collins JK. 1998. Development and application of an in vitro methodology to
determine the transit tolerance of potentially probiotic
Lactobacillus and Bifidobacterium species in the upper
human gastrointestinal tract. Journal of Applied Microbiology 84, 759768.
Gibson GR. 1990. Physiology and ecology of the sulphatereducing bacteria. Journal of Applied Bacteriology 69, 769
797.
Guarner F, Malagelada JR. 2003. Gut flora in health and
disease. Lancet 361, 512519.
Gueimonde M, Margolles A, de los Reyes-Gaviln CG, Salminen S. 2007. Competitive exclusion of enteropathogens
from human intestinal mucus by Bifidobacterium strains
with acquired resistance to bile a preliminary study.
International Journal of Food Microbiology 113, 228232.
Hamada H, Hiroi T, Nishiyama Y, Takahashi H, Masunaga Y,
Hachimura S, Kaminogawa S, Takahashi-Iwanaga H,
Iwanaga T, Kiyono H, Yamamoto H, Ishikawa H. 2002.
Identification of multiple isolated lymphoid follicles on
the antimesenteric wall of the mouse small intestine.
Journal of Immunology 168, 5764.
Hase K, Ohno H. 2006. Epithelial cells as sentinels in mucosal
immune barrier. Japanese Journal of Clinical Immunology
29, 1626.
Heuer OE, Hammerum AM, Collignon P, Wegener HC. 2006.
Human health hazard from antimicrobial-resistant
enterococci in animals and food. Clinical Infectious Diseases
43, 911916.
Heyman M. 2000. Effect of lactic acid bacteria on diarrheal
disease. Journal of the American College of Nutrition 19
(Suppl), 137S146S.
Holdeman LV, Cato EP, Moore WEC. 1974. Anaerobe Laboratory Manual. Virginia Polytechnic Institute and State University, Blacksburg, VA.
Imaoka A, Matsumoto S, Setoyama H, Okada Y, Umesaki Y.
1996. Proliferative recruitment of intestinal epithelial
lymphocytes after microbial colonization of germfree
mice. European Journal of Immunology 26, 945948.
Inoue R, Tsukahara T, Nakanishi N, Ushida K. 2005. Development of the intestinal microbiota in the piglet. Journal
of General and Applied Microbiology 51, 257265.
Inoue R, Ushida K. 2003a. Vertical and horizontal transmission of intestinal commensal bacteria in the rat model.
FEMS Microbiology Ecology 46, 213219.
Inoue R, Ushida K. 2003b. Development of the intestinal
microbiota in rats and its possible interaction with the
evolution of the luminal IgA in the intestine. FEMS Microbiology Ecology 45, 147153.
Isolauri E, Salminen S, Ouwehand AC. 2004. Probiotics. Best
Practice and Research Clinical Gastroenteology 18, 299313.
Isolauri E, Stas Y, Kankaanp P, Arvilommi H, Salminen S.
2001. Probiotics: effects on immunity. American Journal of
Clinical Nutrition 73 (Suppl), 444S450S.
Jang MH, Kweon MN, Iwatani K, Yamamoto M, Terahara K,
Sasakawa C, Suzuki T, Nochi T, Yokota Y, Rennert PD,
Hiroi T, Tamagawa H, Iijima H, Kunisawa J, Yuki Y,
Kiyono H. 2004. Intestinal villous M cells: an antigen
entry site in the mucosal epithelium. Proceedings of the
National Academy of Sciences of United States of America 101,
61106115.
Jensen BB, Jrgensen H. 1994. Effects of dietary fiber on
microbial activity and microbial gas production in various
regions of the gastrointestinal tract of pigs. Applied and
Environmental Microbiology 60, 18971904.
Kaila M, Isolauri E, Soppi E, Virtanen E, Laine S, Arvilommi
H. 1992. Enhancement of the circulating antibody secret-
ing cell response in human diarrhea by a human Lactobacillus strain. Pediatric Research 32, 141144.
Kaisho T, Akira S. 2002. Toll-like receptors as adjuvant
receptors. Biochimica et Biophysica Acta 1589, 113.
Kaneko T, Mori H, Iwata M, Meguro S. 1994. Growth stimulator for Bifidobacteria produced by Propionibacterium
freudenreichii and several intestinal bacteria. Journal of
Dairy Science 77, 393404.
Kitazawa H, Thono M, Shimosato T, Saito T. 2008. Development of molecular immunoassay system for probiotics via
toll-like receptors based on food immunology. Animal
Science Journal 79, 1121.
Kramer DR, Cebra JJ. 1995. Early appearance of Natural
mucosal IgA responses and germinal centers in suckling
mice developing in the absence of maternal antibody.
Journal of Immunology 154, 20512062.
Kuchta RD, Abeles RH. 1985. Lactate reduction in Clostridium
propionicum. Purification and properties of lactyl-CoA
dehydratase. Journal of Biological Chemistry 260, 13181
13189.
Lee YK, Lim CY, Teng WL, Ouwehand AC, Tumola EM,
Salminen S. 2000. Quantitative approach in the study of
adhesion of lactic acid bacteria to intestinal cells and their
competition with enterobacteria. Applied and Environmental Microbiology 66, 36923697.
Leser TD, Amenuvor JZ, Jensen TK, Rh L, Boye M, Mller K.
2002. Culture-independent analysis of gut bacteria: the
pig gastrointestinal tract microbiota revisited. Applied and
Environmental Microbiology 68, 673690.
Leser TD, Lindecrona RH, Jensen TK, Jensen BB, Mller K.
2000. Changes in bacterial community structure in the
colon of pigs fed different experimental diets and after
infection with Brachyspira hyodysenteriae. Applied and
Environmental Microbiology 66, 32903296.
Link-Amster H, Rochat F, Saudan KY, Mignot O, Aeschlimann JM. 1994. Modulation of a specific humoral
immune response and changes in intestinal flora mediated through fermented milk intake. FEMS Immunology
and Medical Microbiology 10, 5563.
Ljungh , Wadstrm T. 2005. Lactic acid bacteria as probiotics. Current Issues in Intestinal Microbiology 7, 7390.
Lu L, Walker WA. 2001. Pathologic and physiologic interactions of bacteria with the gastrointestinal epithelium.
American Journal of Clinical Nutrition 73 (Suppl), 1124S
1130S.
Lunney JK. 2007. Advances in swine biomedical model
genomics. International Journal of Biological Science 3, 179
184.
Macfarlane GT, Cummings JH. 1999. Probiotics and prebiotics: can regulating the activities of intestinal bacteria
benefit health? British Medical Journal 318, 9991003.
Mackie RI, Gilchrist FM. 1979. Changes in lactate-producing
and lactate-utilizing bacteria inrelation to pH in the
rumen of sheep during stepwise adaptation to highconcentrate diet. Applied and Environmental Microbiology
38, 422430.
Mackie RI, Sghir A, Gaskins HR. 1999. Developmental microbial ecology of the neonatal gastrointestinal tract. American
Journal of Clinical Nutrition 69 (Suppl), 1035S1045S.
Madec F, Bridoux N, Bounaix S, Jestin A. 1998. Measurement of digestive disorders in the piglet at weaning and
Seeliger S, Janssen PH, Schink B. 2002. Energetics and kinetics of lactate fermentation to acetate and propionate via
methylmalonyl-CoA or acrylyl-CoA. FEMS Microbiology
Letters 211, 6570.
Sethi AK, Sarna S. 1995. Contractile mechanisms of canine
colonic propulsion. American Journal of Physiology 268,
G530G538.
Sevin AL. 2004. Antagonistic activities of lactobacilli and
bifidobacteria against microbial pathogens. FEMS Microbiology Reviews 28, 405440.
Shroff KE, Meslin K, Cebra JJ. 1995. Commensal enteric
bacteria engender a self-limiting humoral mucosal
immune response while permanently colonizing the gut.
Infection and Immunity 63, 39043913.
Stevens CE, Hume ID. 1995. Comparative Physiology of the
Vertebrate Digestive System, 2nd edn, Cambridge University
Press, Cambridge.
Sui J, Leighton S, Busta F, Brady L. 2002. 16S ribosomal
DNA analysis of the faecal lactobacilli composition of
human subjects consuming a probiotic strain Lactobacillus
acidophilus NCFM. Journal of Applied Microbiology 93,
907912.
Takahashi S, Egawa Y, Simojo N, Tsukahara T, Ushida K.
2007. Oral administration of Lactobacillus plantarum strain
lq80 to weaning piglets stimulates the growth of indigenous lactobacilli to modify the lactobacillal population.
Journal of General and Applied Microbiology 53, 325332.
Tannock GW. 1995. Role of probiotics. In: Gibson GR, Macfarlane GT (eds), Human Colonic Bacteria: Role in Nutrition,
Physiology and Pathology, pp. 257271. CRC Press, London.
Tannock GW, Munro K, Harmsen HJ, Welling GW, Smart J,
Gopal PK. 2000. Analysis of the fecal microflora of human
subjects consuming a probiotic product containing Lactobacillus rhamnosus DR20. Applied and Environmental Microbiology 66, 25782588.
Tsukahara T, Bukawa W, Kan T, Ushida K. 2005. Effect of a
cell preparation of Enterococcus faecalis strain EC-12 on
digesta flow and recovery from constipation in a pig
model and human subjects. Microbial Ecology in Health and
Disease 17, 107113.
Tsukahara T, Hashizume K, Koyama H, Ushida K. 2006.
Stimulation of butyrate production through the metabolic
interaction between lactic acid bacteria, Lactobacillus acidophilus, and lactic acid utilizing bacteria, Megasphaera elsdenii
in the pig cecal digesta. Animal Science Journal 77, 454461.
Tsukahara T, Iwasaki Y, Nakayama K, Ushida K. 2003.
Stimulation of butyrate production in the large intestine
371