CHAPTER 19
Probiotics
Introduction
Probiotics are living organisms that, when ingested in large enough number, are beneficial to the host. The concept of beneficial organisms dates to over 100 hundred years ago, when the Russian scientist Elie Metchnikoff postulated that lactic acid bacteria could promote longevity, evidently inspired by observing the long life span of Russians in the Caucasus who ate a lot of yogurt. Even before antibiotics had been developed, the German scientist Alfred Nissle isolated a strain of Escherichia coli from a World War I soldier who did not develop dysentery while many others around him did. This E. coli strain, called E. coli Nissle 1917, has been used as a probiotic for many decades. The term “probiotic” became widely used in 1989, when Fuller introduced the idea that they have a beneficial effect on the host. There has been a marked increase in interest in probiotics and their possible health benefit in the western world in the last 20 years due to the appeal of “natural” products (Table 19.1).
Table 19.1 Common commercially available probiotic products
| Product | Components | CFU count/dose |
| Culturelle® | Lactobacillus rhamnosus GG | 10 billion |
| DanActive® Yogurt | Lactobacillus casei | 10 billion |
| Align® | Bifidobacter infantis | 1 billion |
| Mutaflor® | Escherichia coli Nissle 1917 | 2–25 billion |
| VSL #3® | Bifidobacterium breve, B. longum, B. infantis, Lactobacillus acidophilus, B. plantarum, L. paracasei, L. bulgaricus, Streptococcus thermophilus | 450 billion combined |
| Yakuit® | L. casei shirota, B. breve | 6.5 billion |
| Florastor® | Saccharomyces boulardii | 5 billion |
| CFU, colony forming units. | ||
The minimum criteria for defining any probiotic is specifying its specific genus and strain, quantifying numbers of viable organisms, confirming they are delivered in adequate numbers to the intestinal tract, with good reliability between batches, and have been found efficacious and safe in human studies.
Probiotics must survive passage through the GI tract, and reach the intestine in viable numbers, and thus should be able to resist gastric acid and bile to reach and colonize the intestine.
Pharmacology
Most probiotics are bacteria, commonly Lactobacillus and Bifidobacteria, although one is a yeast (Saccharomyces boulardii). Some strains of bacteria have been developed from human sources. Probiotic microbes are characterized by genus and species, and then the specific strain is designated alphanumerically. Some bacterial strains have been genetically engineered to produce immunomodulators, such as interleukin-10.
Lactobacilli are associated with fermented foods such as milk. Many Bifidobacteria are added to foods as probiotic organisms, others are marketed as drugs or food supplements. Because each organism is unique, studies should be conducted with specific strains. For example, results from one strain of Bifidobacteria cannot be generalized to others. Moreover, research should evaluate specific numbers of viable organisms and delivery methods, and efficacy should be confirmed in well-designed randomized controlled trials with adequate numbers of patients enrolled. Unfortunately, many products are marketed without such rigorous research.
Products can contain single organisms or combinations of organisms. Dosing is calculated by colony forming units (CFU), that correlates with the numbers of viable organisms, and which is usually reported as per capsule or by weight of the product. Doses should be based on clinical trials that document efficacy.
Mechanisms of action
The precise mechanisms of action of many probiotics have not been elucidated, and different organisms possess many different properties. However, it is often not known if the mechanisms of action of the organism are actually responsible for the beneficial effect of the probiotics. The properties of organisms include the following:
Experts suggest that all probiotic bacteria be genetically sequenced. There is a lactic acid bacteria genome sequencing consortium in the USA, and several bifidobacteria strains have been sequenced as well. Genes have been identified that are associated with characteristics that may correlate with efficacy. They correlate with the ability to survive osmotic, acid, bile and oxidative stress. Other genes regulate cell surface factors that may affect adherence, pathogen exclusion, mucosal integrity and host immune factors.
The probiotic manufacturing process is quite variable; functional foods are a rapidly growing market. Most are developed as dairy products, but also as energy bars and dietary supplements. Products can be fermented, freeze dried, lyophilized, and some require refrigeration.
Clinical indications (Table 19.2)
Probiotics have been evaluated in many clinical conditions affecting the GI tracts. There are several excellent reviews (see Ciorba, 2012; Ringel et al., 2012), as well as Cochrane analyses.
Table 19.2 Evidence-based indications for probiotics in GI diseases
| Product | Efficacy | |
| Treatment of infectious diarrhea in children | Lactobacillus rhamnosus GG L. reuteri ATCC 55730, L. casei DN-114001, S. boulardii | Moderate |
| Prevention of infectious diarrhea in children and adults | Lactobacillus GG, L. casei DN-114001 S. boulardii | Weak |
| Prevention of Traveler’s diarrhea | Lactobacillus GG, Saccharomyces boulardii | Moderate |
| Prevention of AAD Children and adults | Lactobacillus GG
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