Review article
Probiotics: potential pharmaceutical applications

https://doi.org/10.1016/S0928-0987(01)00209-3Get rights and content

Abstract

Realisation of the importance of human gut microbiota in health restoration and maintenance has kindled an interest in probiotics. Probiotics are defined as the microbial food supplements, which beneficially affect the host by improving its intestinal microbial balance. Probiotics are the health enhancing functional food ingredients used therapeutically to prevent diarrhea, improve lactose tolerance and modulate immunity. They may also have potential to prevent cancer and lower serum cholesterol levels. Lactobacillus, Bifidobacterium and several other microbial species are perceived to exert such effects by changing the composition of the gut microbiota. However, it is important that exogenously administered bacteria reach and establish themselves in the large intestine in an intact form. The use of non-digestible oligosaccharides (‘prebiotics’) can fortify intestinal microflora and stimulate their growth. The present review encompasses information regarding the probiotics and their proposed uses. It addresses the concepts of prebiotics and synbiotics, the application of genetic engineering to produce newer probiotics. Finally, the list of commercially available products are reviewed with discussion of questions regarding the reliability, utility and the safety of these products.

Introduction

Probiotics are defined as the viable microorganisms that exhibit a beneficial effect on the health of the host by improving its intestinal microbial balance. The term probiotics was first coined by Lilly and Stillwell in 1965 in reference to substances produced by protozoa, which stimulated the growth of other organisms. Interest in probiotics has been spurred by the growing abundance of modern disorders such as neoplasms, atherosclerosis, cardiac diseases, hypertension and HIV infection. Probiotic consumption is reported to exert a myriad of beneficial effects including: enhanced immune response, balancing of colonic microbiota, vaccine adjuvant effects, reduction of fecal enzymes implicated in cancer initiation, treatment of diarrhea associated with travel and antibiotic therapy, control of rotavirus and Clostridium difficile-induced colitis and prevention of ulcers related to Helicobacter pylori. Probiotics are also implicated in the reduction of serum cholesterol, the antagonism against food-borne pathogens and tooth decay organisms, the amelioration of lactose malabsorption symptoms as well as candidiasis and urinary tract infections (Saavedra, 2001). Promising probiotic strains include the members of genera Lactobacillus, Bifidobacterium, and Enterococcus. The representative species include Lactobacillus acidophilus, L. johnsonii, L. casei, L. gasseri, L. plantarum, L. rhamnosus, Bifidobacterium longum, Bifidobacterium breve, Bifidobacterium bifidum, Bifidobacterium infantis, Enterococcus faecalis and Enterococcus faecium (Fuller, 1991, Gordin and Gorbach, 1992). They have considerable potential for further inclusion in functional foods and health-related products. Even though these health claims are generally accepted by scientists and consumers, however the underlying molecular mechanisms remain controversial. An in depth investigation of the molecular basis of probiotic traits will give a vital reinforcement to the probiotic concept and is a pre-requisite for their rational development.

Section snippets

Properties and proposed mechanism of action

A group of requirements have been identified for a microorganism to be defined as an effective probiotic (Salminen et al., 1996). These include the ability to: (a) adhere to cells; (b) exclude or reduce pathogenic adherence; (c) persist and multiply; (d) produce acids, hydrogen peroxide, and bacteriocins antagonistic to pathogen growth; (e) be safe, noninvasive, noncarcinogenic and nonpathogenic; and (f) coaggregate to form a normal balanced flora.

Emerging evidences have revealed that

Expected therapeutic uses

The commercial interest in functional foods that contain probiotics, is paralleled by increasing study of their role in the digestive tract. To date, interest in probiotic containing foods has centered around three health propositions (a) improving general gut health, (b) improving body’s natural defenses, and (c) lowering blood cholesterol.

Recombinant probiotic — subalin

A new probiotic class based on recombinant strains of bacteria has been designed to produce predetermined therapeutic proteins. The biological properties of Bacillus subtilis 2335 strain were transformed by the plasmid encoding the synthesis of human interferon alpha-2. The recombinant strain was demonstrated to preserve the high antagonistic activity of the parent culture (biosporin) and to acquire marked antiviral properties due to interferon synthesis. Using this strain, Sorokulova et al.

Prebiotics

It is a well-established fact that resistance to pathogens and an immune stimulation can be achieved by probiotic therapy. However, it is important that these exogenous bacteria (i.e. probiotics) reach the large intestine in an intact and viable form. Upon ingestion, these probiotics are confronted by a number of physical and chemical barriers such as gastric and bile acids. As a result only a small proportion of the probiotic microorganisms are able to reach and establish themselves in the

Conclusions and future perspectives

The global market for functional foods is growing at a very fast rate and the probiotic products represent a potential growth area. Intense research efforts are under way to develop products into which probiotic organisms such as Lactobacillus and Bifidobacterium species are incorporated. The long term exploitation of probiotics would depend on scientifically proven clinical evidence of health benefit, of consumer expectation and of effective marketing strategies (Stanton et al., 2001).

One

References (58)

  • H. Majamaa et al.

    Probiotics: a novel approach in the management of food allergy

    J. Allergy Clin. Immunol.

    (1997)
  • B. Mombelli et al.

    The use of probiotics in medical practice

    Int. J. Antimicrob. Agents

    (2000)
  • V.I. Morata de Ambrosini et al.

    Study of adhesion of Lactobacillus casei CRL 431 to ileal intestinal cells of mice

    J. Food Prot.

    (1999)
  • M. Pochapin

    The effect of probiotics on Clostridium difficile diarrhea

    Am. J. Gastroenterol.

    (2000)
  • B.S. Reddy

    Possible mechanisms by which pro- and prebiotics influence colon carcinogenesis and tumor growth

    J. Nutr.

    (1999)
  • B.J. Rembacken et al.

    Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: a randomised trial

    Lancet

    (1999)
  • J.M. Saavedra

    Probiotics and infectious diarrhea

    Am. J. Gastroenterol.

    (2000)
  • J.M. Saavedra

    Clinical application of probiotic agents

    Am. J. Clin. Nutr.

    (2001)
  • M. Schultz et al.

    Probiotics and inflammatory bowel diseases

    Am. J. Gastroenterol.

    (2000)
  • M.P. Taranto et al.

    Evidence for hypocholesterolemic effect of Lactobacillus reuteri in hypercholesterolemic mice

    J. Dairy Sci.

    (1998)
  • M.V. Tejada-Simon et al.

    Proinflammatory cytokine and nitric oxide induction in murine macrophages by cell wall and cytoplasmic extracts of lactic acid bacteria

    J. Food Prot.

    (1999)
  • M.V. Tejada-Simon et al.

    Ingestion of yogurt containing Lactobacillus acidophilus and Bifidobacterium to potentiate immunoglobulin A responses to cholera toxin in mice

    J. Dairy Sci.

    (1999)
  • N.V. Cherdyntseva et al.

    Modulation of the antitumor effect of cyclophosphamide by the recombinant probiotic Subalin

    Vopr. Onkol.

    (1997)
  • G.P. Davidson et al.

    Probiotics in paediatric gastrointestinal disorders

    Curr. Opin. Pediatr.

    (2000)
  • M. Ferencik et al.

    Successful modification of human intestinal microflora with oral administration of lactic acid bacteria

    Bratisl. Lek. Listy.

    (1999)
  • M.J. Friedrich

    A bit of culture for children: probiotics may improve health and fight diseases

    J. Am. Med. Assoc.

    (2000)
  • R. Fuller

    Probiotics in human medicine

    Gut

    (1991)
  • P.K. Gopal et al.

    Oligosaccharides and glycoconjugates in bovine milk and colostrums

    Br. J. Nutr.

    (2000)
  • B.R. Gordin et al.

    Probiotics for humans

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