ReviewMonostrain, multistrain and multispecies probiotics—A comparison of functionality and efficacy☆
Introduction
There is ample evidence from laboratory experiments that ingestion of probiotic microbes, especially lactic acid bacteria and bifidobacteria, alleviates or prevents various disorders, such as lactose intolerance, rotavirus diarrhoea and atopy (Ouwehand et al., 2002a). Despite this evidence, functionality of the probiotics in practice remains questionable. The main reason may be that commercial probiotic products often do not meet a quality standard in that composition and viability are variable Fasoli et al., 2003, Hamilton-Miller and Shah, 2002, Hamilton-Miller et al., 1999, Temmerman et al., 2003, Weese, 2002. A second major issue in relation to the application of probiotics is the poor evidence for efficacy as based on clinical trials (Klaenhammer and Kullen, 1999).
There are at least three issues that interfere with the identification of specific health effects of probiotics (Klaenhammer and Kullen, 1999). First, the complexity and variability of the gastrointestinal environment in relation to gastrointestinal diseases complicate the description of clear effects of probiotics on health and disease. Secondly, the confusion as to identity, viability and activity of probiotic strains contributes to the misidentification of cultures used in clinical investigations. Thirdly, single probiotic strains (monostrain probiotics) are assumed to induce a multitude of effects among different individuals in a test population.
Functionality of a multistrain probiotic could be more effective and more consistent than that of a monostrain probiotic. Colonization of an ecosystem providing a niche for more than 400 species in combination with individually determined host-factors is anticipated to be more successful with multistrain (multispecies) probiotics than with monostrain preparations. Indeed, Famularo et al. (1999) have envisaged that probiotic preparations containing bacteria of only one strain have little chances of successfully colonizing the GI-tract. Furthermore, probiotics are expected to control multi-factorial diseases demanding a variety of probiotic properties, whereas such properties are strain-specific (Sanders and Huis in't Veld, 1999). Therefore Dunne et al. (1999) and Rolfe (2000) have suggested that probiotics should consist of a combination of strains. In 1992 a group of probiotic experts concluded that the optimal prophylactic culture is a mixed one: ‘Different strains can be targeted toward different ailments and can be blended into one preparation’ (Sanders, 1993). Mixed cultures may contain bacteria that complement each other's health effect and thus have synergistic probiotic properties.
Furthermore, research with probiotic strains aims at unraveling mechanisms of action which can be claimed for one specific strain. The elucidation of underlying mechanisms for multistrain probiotics requires sophisticated study designs that are expensive (Klaenhammer and Kullen, 1999). A further drawback is that most clinical studies are funded by companies with interest in one specific strain only (Sanders and Huis in't Veld, 1999). Finding a single strain with unique properties can lead to patents whereas the clinical effectiveness of multistrain probiotics is not easily patentable.
The aim of this review is to compare the efficacy of multistrain and multispecies probiotics with that of monostrain probiotics. We have been able to identify only a limited number of publications explicitly dealing with this topic, but much more valuable information could be obtained from other publications. In these studies animals or humans with a normal gastrointestinal flora were administered different types of probiotics of the lactic acid bacteria genera. It is important to stress that most studies were not designed to compare the efficacy of multi- versus monostrain probiotics. For the purpose of this review we have created a new set of probiotic definitions regarding their strain composition. Monostrain probiotics are defined as probiotics containing one strain of a certain species, and consequently multistrain probiotics contain more than one strain of the same species or closely related species, for instance Lactobacillus acidophilus and Lactobacillus casei. Multispecies probiotics are defined as containing strains of different probiotic species that belong to one or preferentially more genera, e.g. Lb. acidophilus, Bifidobacterium longum, Enterococcus faecium and Lactococcus lactis.
Section snippets
Effect of different Lactobacillus preparations on growth performance of chickens
Jin et al. (1996) have isolated a total of 42 Lactobacillus strains from tissue fragments excised out of the jejunum, ileum and caecum of chickens. The strains were tested in vitro for their ability to adhere to chicken ileal epithelial cells. Twelve strains of the species Lb. acidophilus, Lactobacillus brevis, Lactobacillus fermentum and Lactobacillus crispatus showed moderate to good ability to adhere. A single strain of Lb. acidophilus (I 26), which was the most adherent of the 12 strains,
Effect of probiotics on fecal bacteria in children treated with the antibiotic ceftriaxone
Zoppi et al. (2001) evaluated the clinical effectiveness of six different commercially available probiotics in preventing or correcting imbalance in the intestinal ecosystem caused by the antibiotic ceftriaxone which was parenterally administered to children to treat upper respiratory tract infections. Use of this antibiotic is known to induce a certain dysbiosis which is characterized by a shift in microbiological numbers representative for the flora of healthy persons (Welling et al., 1991).
Effect of various Lactobacillus fermented milks on the severity of a Salmonella Typhimurium infection in mice
In the 1980s Perdigon and her colleagues have published numerous studies on the effect of Lactobacillus fermented milk on the immune system in mice. In one study Perdigon et al. (1990) tested the protective effect of milk fermented with either Lb. acidophilus, Lb. casei or a combination of both strains in mice challenged with Salmonella Typhimurium. Mice were fed for 8 days one of the fermented products followed by an oral challenge with S. Typhimurium. The fermented milks were administered as
Effect of Lb. casei strains alone or in combination on survival in mice challenged with Salmonella Typhimurium
Paubert-Braquet et al. (1995) used mice orally infected with Salmonella Typhimurium to test the protective effect of milks fermented with different strains of the Lb. casei species, yogurt ferments or a combination of both kinds of ferments. The bacterial contents of the test preparations are presented in Table 4 (see footnote). Mice were supplemented for a 7-day period with one of the fermented milks, standard milk or received no supplement. Then the mice were orally infected with S.
Efficacy of different probiotic bacteria in reducing E. coli O157:H7 shedding by sheep
E. coli O157:H7 is an enterohemorrhagic type of E. coli commonly implicated in human food-borne illness. This serotype is particularly dangerous because of its low infectious dose, and its unusual acid tolerance. E. coli O157:H7 is frequently harboured in apparently healthy ruminants. It has been suggested that the fasting of ruminants just before slaughter can induce an increase in ruminal fluid pH because of a lack of easily fermentable sugars for microbial acid production, resulting in
The effect on growth of mono- versus multistrain/multispecies probiotics in rats challenged with Salmonella Enteritidis
We have conducted an experiment in rats challenged with Salmonella Enteritidis to compare the protection induced by a monostrain probiotic versus that induced by multistrain and/or multispecies probiotics (Van Es and Timmerman, 2002). In the experiment male Wistar (U-WU) rats were challenged with a single oral dose of 1.0×109 S. Enteritidis. Before challenge the rats were trained to ingest their restricted amount of daily feed within 1 h. The diets were administered as freshly prepared
Possible mechanisms involved in multispecies probiotics
Knowing that health effects of probiotics are genera, species and strain specific (Sanders and Huis in't Veld, 1999) it could be suggested that multistrain and/or multispecies probiotics may be more effective than monostrain probiotics. In this review it is investigated whether probiotics consisting of more than one strain of the same species or genus (named multistrain or multispecies probiotics) are superior to monostrain probiotics. The studies described indeed provide evidence for
Conclusive remarks
With this review we tried to show the relevance of developing multispecies probiotics which may have improved functionality as compared to single strain probiotics. It is clearly shown that multispecies preparations have advantages when compared to monostrain probiotics or, to a lesser extent, multistrain probiotics. Well-designed multispecies probiotics can benefit from a certain amount of synergism when different probiotic effects of different probiotic species are combined. The activity can
Acknowledgements
The research was supported partly by the Dutch Ministry of Economic Affairs (SENTER) and Winclove Bio Industries, Amsterdam, The Netherlands. The authors would like to thank Mrs. I. Lemmens and Mr. R. Blankenstein for their technical assistance.
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Taxonomic names are used according to the present nomenclature as published by the Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, Germany (DSMZ; www.dsmz.de).