Each day in the United States of America alone, an estimated 190 million doses of antibiotics are given to humans, and an equal volume given to livestock. This astounding use of antibiotics, for the most part, is not to fight diseases, but rather to ostensibly prevent it, or in the case of animals enhance growth. It is therefore not surprising that the incidence of drug resistant bacteria is increasing to the extent that levels of resistance to fluoroquinolones, penicillins and co-trimoxazole are preventing effective treatment of many diseases.
This past May in a small town in Ontario Canada, an outbreak of E. coli 0157 poisoning from the water supply caused 7 deaths and much morbidity. These organisms were believed to have come from cattle feces. Antibiotic therapy for this organism can worsen the illness and cause hemolytic uremic syndrome. Thus, it could be argued that antibiotic treatment of cattle and of ill patients, is not an optimal remedy for control of certain pathogens.
While antibiotics have a large list of side effects, some of which are fatal, probiotics (use of viable organisms with host benefits) have next to none. The concept of using probiotics to colonize newborn cows has long been espoused with some success, but in humans especially newborns prone to necrotising enterocolitis, almost no studies with probiotics have been undertaken. There is evidence that use of probiotic lactobacilli can prevent and reduce the duration of diarrhea in adults and children, while in vitro studies show that certain strains can inhibit growth of E. coli 0157. So, why are probiotics not widely used in North America?
The concept of eating bacteria is foreign to the rather clean cut North American culture, yet an integral part of the lifestyle of many European and Asian countries. Indeed, successful probiotic products are almost exclusively made by Japanese, Swiss, French and Scandinavian companies. The delivery vehicles are primarily yogurt and drinks, because of the expertise of the companies and the regulatory ease with which foods can be marketed compared to pharmaceuticals. The question is do they have any value? Unfortunately, there are no long term studies on the impact of probiotics on general health and well-being, although there is growing evidence that certain products confer specific benefits.
For the consumer, selecting a "good" probiotic that is reliable, safe, with scientifically-proven contents, is not easy, in part because of restrictions on labeling claims and also because too few strains have undergone any efficacy testing. Thus, many so-called probiotic products in the UK have recently been exposed as useless.
The critical point that must be addressed if probiotics in general and specific products are to be widely accepted, is the publication in peer-reviewed journals of efficacy data and mechanisms of action. Of the hundreds of strains currently in use, only a handful have any published data which suggests they are useful in humans. Of these, Lactobacillus rhamnosus GG, L. casei Shirota, L. casei CRL431 and to a much lesser extent L. johnsonii LA1 and L. plantarum 299V have some verified attributes. All are available as dairy products designed to confer some sort of benefit to the intestinal tract.
The focus of our studies for the past 18 years has been the urogenital tract, the site of infections by bacteria and yeasts in an estimated one billion women each year. Three strains, L. rhamnosus GR-1, L. fermentum RC-14 and L. fermentum B-54 have been shown to possess anti-pathogen properties and to colonize and benefit women. The last point is important, as clearly not all probiotic organisms possess properties optimal for the urogenital tract. Our most recent studies have utilized strains GR-1 and RC-14 in combination, as they resist spermicides (GR-1) and produce hydrogen-peroxide and biosurfactants (RC-14) which are factors in host protection. These strains also colonize the intestine and can thus potentially be intestinal, as well as urogenital, probiotics.
Many aspects of probiotic R&D are essential for success but rarely discussed: namely, selection of strains and target ailments, successful upscale manufacturing, storage and shelf-life, and regulatory approvals.
1. The first point has been made, and it is up to producers of probiotics to obtain the necessary conclusive evidence that their strains have any beneficial effect on the host, or any differential attributes over other strains.
2. Lactobacillus and Bifidobacterium strains, used mostly in probiotics, are difficult to grow and more difficult to scale-up and freeze-dry or lyophilize or deliver in high viable numbers. Thus, all too often products are not viable or have insufficient numbers of viable bacteria to confer anything of value to the host. Also, few strains pass the acid pH of the stomach and the effects of bile salts, thus viability alone is not sufficient. Yogurts and other dairy products are usually made with lactic acid cultures, then probiotic organisms are added. Viability should then be maintained for a period of around 6-7 weeks (thus the sell-by date). This provides the consumer with a tasty nutrient which can be part of his/her diet. However, more optimal delivery systems could improve the health benefit to the consumer or patient. Shelf-life and storage is restricted for dairy products, because of the requirement for refridgeration. Also, shelf-life in Europe is tested at 20C while in the US is should be at 25C.
3. Government regulations differ in every country, but for the most part probiotics come under dietary supplements because most are delivered by mouth as foods (thus the term functional foods). However, as probiotics are being applied to other areas (wounds, skin, urogenital tract etc), such regulations need to be revisited. Most companies get around legislation (which is made for claims on labels and packages) by using web sites, brochures, adverts and other means to associate their products with healthy benefits. One problem with this system is that consumers then associate a particular product with scientific proof of efficacy, when in fact the proof was obtained using other strains.
Marketing surveys show that North America is prime for probiotic products, and women in particular are demanding natural remedies to prevent disease and restore and maintain health. There seems little doubt that probiotics will become part of a global health supplement approach. The question is, will properly tested products be used, long term follow-up studies published and scientific investigations into mechanisms of action be funded? Time will tell.