Safe and efficacious probiotics: what are they?

doi:10.1016/j.tim.2006.06.006

Trends in Microbiology

Volume 14, Issue 8, August 2006, Pages 348-352

https://doi.org/10.1016/j.tim.2006.06.006 Get rights and content

Each year, >20 billion doses of probiotics are used by healthy people and by those diagnosed with a range of medical conditions. Compared to many pharmaceutical agents, probiotics are well tolerated and extremely safe, and serious adverse effects rarely occur. Nevertheless, as many new researchers enter the field and companies launch ‘probiotic’ products, it is essential that standards are set for naming a product ‘probiotic’ to show that it meets an acceptable level of safety and efficacy, and to understand the strengths and limitations of its activity. In this Opinion article, recommendations are made based upon the current understanding of scientific, clinical and regulatory issues, with a special focus on safety.

Section snippets

Key to the future of probiotics

The number of scientific publications on probiotics has doubled in the past three years and this recent interest [1] has been further stimulated by several factors: (i) exciting scientific and clinical findings using well documented probiotic organisms; (ii) concerns over limitations and side effects of pharmaceutical agents; and (iii) consumer demand for natural products. All this has led to predictions of a tripling in sales by 2010 (European and US Probiotics Market research, 6 August 2003; //www.frost.com/

Definition and guidelines for use of the term ‘probiotic’

A number of definitions of the term ‘probiotic’ have been used over the years but the one derived by the Food and Agriculture Organization of the United Nations–World Health Organization (FAO–WHO) [2] and endorsed by the International Scientific Association for Probiotics and Prebiotics [3] best exemplifies the breadth and scope of probiotics as they are known today: “Live microorganisms, which when administered in adequate amounts, confer a health benefit on the host”. This definition retains

The importance of safety within the guidelines

Safety is the state of being certain that adverse effects will not be caused by an agent under defined conditions. The reciprocal of safety is risk. The issue of safety for any product is arguably paramount during pregnancy and in newborn babies. The best example of the safe use of probiotics during pregnancy is that of Lactobacillus rhamnosus GG, which was used in 132 women who were at high risk of their newborn babies developing atopic dermatitis [9]. Two interesting outcomes relevant to

Reducing the risk of adverse effects caused by probiotic organisms

A better understanding of the potential mechanisms whereby probiotic organisms might cause adverse effects will help to develop effective assays that predict which strains might not be suitable for use in probiotic products. Enhanced understanding will also improve guidelines for the use of specific products and will aid in pointing out clinical situations where probiotic use should be closely monitored.

Concluding remarks and future perspectives

For the most part, probiotic strains are safe and well tolerated by humans of various ages. Rare cases of bacteremia have arisen and have been successfully treated with antibiotics, except in some patients with serious underlying diseases. No generalized warnings come with probiotic products and, at present, it would be difficult to deduce which warnings, if any, would be appropriate. Nevertheless, product labeling should contain more specific guidelines for consumers. These could include

Acknowledgements

Funding for the Canadian R&D Centre for Probiotics was provided by the Natural Sciences and Engineering Research Council, the Ontario Challenge Fund, the Ontario Ministry of Agriculture and Food and Wyeth Ayerst.

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Probiotics are live microbial or culture product feed supplements that have beneficial effects on the health of the host when consumed in adequate doses [11]. Probiotics are known to be beneficial in enhancing immune response, competing for nutrition and energy with pathogens, secreting inhibitory and antibacterial substances (i.e. bacteriocins), and providing nutrients and enzymatic contributions on their hosts, as well as improving water quality in an aquaculture system [12,13]. Within the wide range of probiotics studied, lactic acid bacteria (LAB) have aroused to be important in recent years.
Mud crabs (Scylla paramamosain), a commercially important cultured species in the southeastern region of China, is usually infected by Vibriosis or parasites, causing great economic losses in cultured farms. Previous studies have demonstrated that probiotics benefited in enhancing the immune response against invading pathogens in aquatic animals. In this study, the effects of dietary administration of lactic acid bacteria (LAB) (Enterococcus faecalis Y17 and Pediococcus pentosaceus G11) on growth performance and immune responses of mud crab were assessed. Both strains (Y17 and G11) showed an inhibitory activity against bacterial pathogens (Aeromonas hydrophila, Vibrio parahaemolyticus, Vibrio alginolyticus, Staphylococcus aureus, and β Streptococcus), and a wide pH tolerance range of 2–10. In vivo, mud crabs were fed a control diet and experimental diets supplemented with 10⁹ cfu g⁻¹ diet either Y17 or G11 for 6 weeks before subjecting to a challenge test with V. parahaemolyticus for 12 h. The probiotic-supplemented diets had significant effects on weight gain and specific growth rate during the feeding trial. Increased serum enzyme activities of phenoloxidase, lysozyme, and SOD were observed in the hemolymph of mud crab in Y17 and G11-supplemented groups compared to that in the controls (P < 0.01). The significantly up-regulated expression of gene CAT, LYS, proPO, and SOD could be seen in hepatopancreas in G11-supplemented groups. After the pathogenicity test, the survival rate of Y17 + and G11 + V. parahaemolyticus groups was 66.67% and 80.00%, respectively, compared with 53.33% for the control groups. Taken together, dietary supplementation of Y17 and G11 strains were beneficial in mud crab, which could increase growth performance, modulate immune system and protect the host against V. parahaemolyticus infection.
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In a previous study, bacterial communities of the intestine in three populations of crabs (wild crabs, pond-raised healthy crabs and diseased crabs) were probed by culture-independent methods. In this study, we examined the intestinal communities of the crabs by bacterial cultivation with a variety of media. A total of 135 bacterial strains were isolated from three populations of mud crabs. The strains were screened for antagonistic activity against Vibrio parahaemolyticus using an agar spot assay. Antagonistic strains were then identified by 16S rRNA gene sequence analysis. Three strains (Bacillus subtilis DCU, Bacillus pumilus BP, Bacillus cereus HL7) with the strongest antagonistic activity were further evaluated for their probiotic characteristics. The results showed that two (BP and DCU) of them were able to survive low pH and high bile concentrations, showed good adherence characteristics and a broad spectrum of antibiotic resistance. The probiotic effects were then tested by feeding juvenile mud crabs (Scylla paramamosain) with foods supplemented with 10⁵ CFU/g of BP or DCU for 30 days before being subjected to an immersion challenge with V. parahaemolyticus for 48 h. The treated crabs showed significantly higher expression levels of immune related genes (CAT, proPO and SOD) and activities of respiratory burst than that in controlled groups. Crabs treated with BP and DCU supplemented diets exhibited survival rates of 76.67% and 78.33%, respectively, whereas survival rate was 54.88% in crabs not treated with the probiotics. The data showed that indigenous mud-associated microbiota, such as DCU and BP, have potential application in controlling pathogenic Vibriosis in mud crab aquaculture.
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To shed light on the interactions occurring in fermented milks when using co-cultures of Streptococcus thermophilus with Lactobacillus bulgaricus (StLb) or Lactobacillus acidophilus (StLa), a new co-metabolic model was proposed and checked either in the presence of inulin as a prebiotic or not. For this purpose, the experimental data of concentrations of substrates and fermented products were utilized in balances of carbon, reduction degree and ATP. S. thermophilus exhibited always quicker growth compared to the other two microorganisms, while the percentage of lactose fermented to lactic acid, that of galactose metabolized, and the levels of diacetyl and acetoin formed strongly depended on the type of co-culture and the presence of inulin. The StLb co-culture led to higher acetoin and lower diacetyl levels compared to StLa, probably because of more reducing conditions or limited acetoin dehydrogenation. Inulin addition to StLa suppressed acetoin accumulation and hindered that of diacetyl, suggesting catabolite repression of α-acetolactate synthase expression in S. thermophilus. Both co-cultures showed the highest ATP requirements for biomass growth and maintenance at the beginning of fermentation, consistently with the high energy demand of enzyme induction during lag phase. Inulin reduced these requirements making biomass synthesis and maintenance less energy-consuming. Only a fraction of galactose was released from lactose, consistently with the galactose-positive phenotype of most dairy strains. The galactose fraction metabolized without inulin was about twice that in its presence, which suggests inhibition of the galactose transport system of S. thermophilus by fructose released from partial inulin hydrolysis.
State of the art in benefit-risk analysis: Food microbiology
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They are rarely associated with disease, and are thought to have low pathogenicity (Bernardeau et al., 2008). Yet, some studies have shown that a small portion of the population may be at risk of adverse effects following probiotic administration (Reid, 2006; Besselink et al., 2008; Sanders et al., 2010). Immunicompromised patients have for example been found to be susceptible to opportunistic Lactobacillus spp. infections (Husni et al., 1997; Schlegel et al., 1998), although it has not been determined if these Lactobacillus strains are consistent with those found in food.
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Recently, a number of initiatives have been launched in the field of food and nutrition to address the formulation of the benefit–risk assessment approach. BRA has recently been advocated by EFSA for the public health management of food and food ingredients; as beneficial and adverse chemicals can often be found within the same foods and even the same ingredients. These recent developments in the scoping of BRA could be very relevant for food microbiological issues. BRA could become a valuable methodology to support evaluations and decision making regarding microbiological food safety and public health, supplementing other presently available policy making and administrative tools for microbiological food safety management.
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Trends in Microbiology

OpinionSafe and efficacious probiotics: what are they?

Section snippets

Key to the future of probiotics

Definition and guidelines for use of the term ‘probiotic’

The importance of safety within the guidelines

Reducing the risk of adverse effects caused by probiotic organisms

Concluding remarks and future perspectives

Acknowledgements

Microbiol. Res.

Lancet

Nutrition

Lancet

Int. J. Infect. Dis.

Int. J. Food Microbiol.

Cell

Good bugs getting more notice

The Baltimore Sun

New scientific paradigms for probiotics and prebiotics

J. Clin. Gastroenterol.

Probiotics to prevent urinary tract infections: the rationale and evidence

World J. Urol.

Caveat emptor. “Probiotics” might not be what they seem

Can. Fam. Physician

Culture-independent analysis of probiotic products by denaturing gradient gel electrophoresis

Appl. Environ. Microbiol.

Lactobacillus bacteremia, species identification, and antimicrobial susceptibility of 85 blood isolates

Clin. Infect. Dis.

Lactobacillus bacteremia during a rapid increase in probiotic use of Lactobacillus rhamnosus GG in Finland

Clin. Infect. Dis.

Lactobacillus bacteremia, clinical significance, and patient outcome, with special focus on probiotic L. rhamnosus GG

Clin. Infect. Dis.

The efficacy and safety of probiotic Lactobacillus rhamnosus GG on prolonged, noninfectious diarrhea in HIV patients on antiretroviral therapy: a randomized, placebo-controlled, crossover study

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Inflamm. Bowel Dis.

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Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine

Gut

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Clin. Infect. Dis.

How safe is safe? A case of Lactobacillus paracasei ssp. paracasei endocarditis and discussion of the safety of lactic acid bacteria

Scand. J. Infect. Dis.

Opinion
Safe and efficacious probiotics: what are they?