Probiotics research and development has traditionally focused on single strains for specific health applications. Linda Mulder, MSc, says combinations of strains offer product developers new avenues to explore
Do we need one probiotic strain to prevent or treat all kinds of health problems? Or do we need different products to be used in different situations? And when we look at these products, is one probiotic strain enough, or do we need a combination of probiotics strains?
It has been widely accepted that intestinal microflora plays an important role in human health. In 2001, a joint expert committee of the World Health Organization and the Food and Agricultural Organization of the United Nations published a report on the health properties of probiotics.1 In this report, all gastrointestinal-related health problems were mentioned — problems that can possibly be treated or reduced with probiotic supplements. The International Probiotics Workshop last spring in Amsterdam gathered more than 100 experts to take the report?s findings one step further.
Besides problems like diarrhoea, constipation and inflammatory bowel disease, the committee also mentioned allergies, cancer, cardiovascular diseases and urinary tract infections among the health problems related to a disturbed microflora in the GI tract. This is not surprising, because research has shown that the intestinal microflora and probiotic bacteria play an important role in immune system regulation.
One size fits all?
Is it possible to find one probiotic supplement that can be used in the prevention or treatment of this wide variety of problems and diseases? Can one probiotic strain kill pathogenic bacteria, modulate our immune system in the right way and interact with our epithelial cells at the same time? Probably not. Although all mentioned health problems are related to our gastrointestinal tract and intestinal microflora, there are very different mechanisms behind them.
Take a look at two well-known types of diarrhoea: antibiotic-associated diarrhoea (AAD) and travellers? diarrhoea (TD). In the case of AAD, the cause is obvious: the use of antibiotics. In 15-25 per cent of patients who develop AAD, this is caused by an overgrowth of pathogenic Clostridium difficile. If one would select a probiotic strain (or combination of strains) to prevent or treat AAD, an important selection criterion would be the inhibition of Clostridium spp. If one would, on the other hand, develop a product to prevent TD, which is often caused by the enteropathogenic E.coli (ETEC), it is more logical to select strains that can inhibit growth of ETEC. It surely may be possible to find a probiotic bacterium that inhibits both ETEC and Clostridium.
But will this strain be effective in other health problems as well? It might be possible to find a strain that can do ?a bit of everything.? This means that it has potential in many health problems ? but it will never be the most effective product, in either case!
To overcome this problem there are two options: Select the best strains for as many applications as one can think of, and combine them into one probiotic supplement that (theoretically) works in any health problem, or make selective products for specific applications.
The first option has its disadvantages. First, it is almost impossible to think of all possible probiotic applications. As we can see in literature, more and more applications of probiotics are recently being studied to treat a wide range of health conditions, ranging from treating or reducing high cholesterol, to vaginal candida, lactose intolerance and urinary tract infections. Even the effect of probiotics in healthy persons is being studied. The potential application area of probiotics will become more and more broad spectrum when probiotics appear to be effective in more areas.
Secondly, the compatibility of the strains should be taken into account. Within a product containing eight to 20 strains or even more, there is a fair chance that a few dominant strains will rule out the others. Therefore, one cannot be sure whether the right strain will be effective at the right time, in the right place.
This leads to the third disadvantage: Each of the strains is selected for a specific characteristic, such as the inhibition of ETEC, or the induction of a certain immune parameter. However, it is possible that the strain selected for the inhibition of ETEC also produces certain immune parameters that are not desired in the concerning application.
One, two, many
The above mentioned disadvantages do not mean that products with multiple probiotic strains are not desired. On the contrary, the so-called multistrain (containing more strains of the same genera; eg, several Lactobacillus spp.) and multi-species (containing strains of different genera; lactobacilli, bifidobacteria, streptococci, etc.) probiotics have advantages over monostrain probiotics. However, one probiotic supplement that is applicable in any and every thinkable health problem is not realistic.
This leaves the other option — creating different probiotic supplements for specific health problems. The advantage is that those strains can be specifically selected that are (potentially) effective in a certain problem or disease. To select the right strains, it is important that the mechanism behind a certain disease is clear — what is the exact problem and what is the cause of it? In some cases it is not known what the exact cause of the problem is, for instance in IBD.
However, it is known that IBD patients often have an altered microflora and an abnormal immunological host response to normal GI stimuli. In many cases IBD is a colonic problem and the most predominant lactic acid-producing species in the colon are (normally) bifidobacteria. All this information can be useful in selecting the most potential probiotic strains for a probiotic product that reduces IBD symptoms.
Literature and in vitro work will therefore be indispensable for selecting probiotic strains to develop the most effective specific probiotics.
Select the best
This leaves the discussion whether these specific products should contain one effective probiotic strain, two or more probiotic strains, or even strains from different bacterial genera. Literature has shown efficacy of products with one strain, for instance Lactobacillus casei Shirota or Lactobacillus rhamnosus GG, in certain applications. On the other hand, many studies have been described in which a combination of probiotic strains was effective. Studies designed to compare monostrain probiotics and probiotics with multiple strains are rare.
Recently a review by Timmerman et al. was published on the functionality and efficacy of monostrain, multistrain and multispecies probiotics.2 In this review, it was concluded that multispecies probiotics have advantages compared to monostrain probiotics; specifically, that a number of favourable characteristics of individual strains are combined in one probiotic supplement. As mentioned before, it is very important to look at the compatibility of the strains. However, studies have also demonstrated that the combination of probiotic strains can show synergistic effects. For instance the adhesion of Bifidobacterium lactis BB-12 to intestinal cells was more than doubled in the presence of Lactobacillus GG or L. bulgaricus probiotic strains.3
In another study, the adherence of probiotics to human intestinal mucus ranged from one to 34 per cent in healthy subjects as indicated for the following strains: L. rhamnosus GG, 34 per cent; B lactis BB12, 31 per cent; L acidophilus LA5, four per cent; L paracasei F19, three per cent; and L casei Shirota, one per cent. The adhesion of BB12 in the presence of LGG increased from 31 to 39 per cent in healthy infants and, in episodes of diarrhoea, increased from 26 to 44 per cent.4
This evidence supports using multistrain or multispecies probiotic supplements that contain probiotic strains specifically selected for a certain application and tested for their compatibility in the product. These have the best potential to be effective in the prevention, reduction or treatment of a wide variety of health problems.
Other questions still need to be answered: What is the most effective dosage in terms of bacteria concentrations? Shouldn?t we develop probiotic products for each person individually? Which specific strains offer optimal compatibility and health effects?
At the moment it is more important we focus on the development of high-quality probiotics that are stable and effective at the right time and place. This means survival of probiotic strains in the product and survival during passage through the gastrointestinal tract.
Besides that, it is important that the product contains the right characteristics to be effective where it is most desired — in the intestines. This means inhibiting pathogens, interacting with the epithelial cells and/or regulating parts of the immune system. To achieve this, a lot of questions still need to be answered and more research must be conducted.
Linda Mulder, MSc, is in product development and quality assurance at Amsterdam-based Winclove Bio Industries, which develops and produces tailor-made probiotic food supplements for the business-to-business industry. Respond: [email protected]
1. FAO/WHO. 2001. Health and nutritional properties of probiotics in food including powder milk with live lactic acid bacteria. Report of a joint FAO/WHO expert consultation.
2. Timmerman HM, et al. Monostrain, multistrain and multispecies probiotics ? A comparison of functionality and efficacy. Int J Food Microbiol 2004; 96:219-33.
3. Ouwehand AC, et al. 2000. The mucous binding of Bifidobacterium lactis BB-12 is enhanced in the presence of Lactobacillus GG and Lactobacillus delbrueckii spp. bulgaricus. Lett Appl Microbiol 2000 Jan; 30(1):10-3.
4. Juntunen M, et al. Adherence of probiotic bacteria to human intestinal mucus in healthy infants and during rotavirus infection. Clin Diagn Lab Immunol 2001.