Years

Figure 1. Publications on probiotics in the PubMed database. Citations were obtained using "probiotic" or "probiotics" as key words for each of the year(s) indicated. Data for 2005 are through February.

130 Microbiology and Technology of Fermented Foods Box 4β€”5. Sorting Through the Pros and Cons of Probiotics (Continued)

A good example of the nomenclature confusion concerns the organism "Lactobacillus sporo-genes."This organism was described in early editions of Bergey's Manual (prior to 1939), but has since been shown to be a misclassification and now "Lactobacillus sporogenes" is considered to be scientifically invalid (Sanders et al., 2003).

It is important to recognize, however, that just because a given organism is appropriately named does not ensure that the organism has probiotic activity. In other words, while solid evidence may exist to support the probiotic functions of a specific strain of Bifidobacterium bi-fidus or Lactobacillus acidophilus, that does not mean that all strains of those organisms meet the minimum relevant criteria for a probiotic or that they have even been evaluated in any way for probiotic activity (Table 1).

Table 1. Functional characteristics of probiotic bacteria1.

Property

Survival

Colonization

Bio-functional

Safety

Acid tolerance Bile tolerance Stress tolerance

Compatibility with starter culture

Adherence factors

Attachment factors

Prebiotic metabolism

High growth rate

Competition factors

Produce short-chain acids

Immunomodulating

Hypocholesteremic

Antitumorogenic

Enhance gut barrier function

Lactose hydrolysis

Antimicrobial activity

Stimulate mucus production

Avirulent

Noninflammatory

Absence of side-effects

Absence of gene transfer xNote, the desirability of these properties for a given probiotic is target-dependent

In addition, the number and viability of cells present in the food vehicle or formulation may be inadequate to promote a probiotic effect. For example, 109 cells per gram are thought to be the minimum level that should be present in yogurt, although no regulatory requirement currently exists. Moreover, questions have been raised regarding whether bacteria in yogurt actually survive the route through the alimentary system. It was recently reported, for example, that volunteer subjects consuming yogurt daily for two weeks failed to shed yogurt bacteria in their feces at any time during the study (del Campo et al., 2005).Another complication concerns the claim that organisms other than bifidobacteria and lactobacilli may also have probiotic effects. These include organisms not ordinarily associated with growth in the intestinal tract, such as Bacillus, Sporolactobacillus, and Brevibacillus (Sanders et al., 2003).Whether or not these organisms can actually survive digestion and have an impact in the gastrointestinal tract remains uncertain. In addition, enterococci, Escherichia coli, and even yeasts (especially Saccharomyces boulardii) have been similarly promoted as probiotics and are also widely available. Finally,

Box 4β€”5. Sorting Through the Pros and Cons of Probiotics (Continued)

questions have been raised in recent years regarding the safety of lactobacilli and other lactic acid bacteria (despite their long time consumption in foods).

These safety concerns are based mainly on just a few sporadic cases in which probiotic organisms were associated with endocarditis, bacteremia, or other invasive infections or underlying conditions (Borriello et al., 2003). Most of these cases, however, involved immunocomprim-ised or at-risk individuals undergoing treatments that would expose them to any opportunistic microbial agent. Moreover,the genome sequences from several probiotic bacteria are now available (Chapter 2), and no functional virulence factors have yet been identified.

It is important to recognize that some bacteria used as probiotics are intrinsically resistant to antibiotics, and, in some cases, may even harbor antibiotic resistant genes on mobile genetic elements (Temmerman et al., 2003; von Wright, 2005).As noted above, Bacillus cereus may be used as a probiotic, despite the fact that some strains of this species cause foodborne disease. Thus, safety evaluations must be considered for any strain to be used a probiotic.

Making the Case for Probiotics

As noted above, literally thousands of research articles have been published on probiotics, with many suggesting that beneficial health effects occur as a result of consuming probiotics or probiotic-containing foods. However, these studies are frequently criticized for either lacking relevant controls or having relied on poor experimental design. Even when a particular study reports a positive result, it is frequently followed by another study in which such effects are absent.

Therefore, determining which claims are supported by solid scientific evidence and identifying the appropriate criteria to evaluate this evidence have become critical goals (Pathmakanthan et al., 2000; Sanders et al., 2004). Indeed, meta-analyses and other retrospective studies, in which published reports are critically evaluated, indicate that while some claims are weakly supported by experimental or clinical data, others appear to be more convincing (Tables 2 and 3).

Table 2. Probiotics: evidence for intestinal health benefits1.

Reasonable evidence Suggestive evidence Potential use

Inflammatory bowel disease Pouchitis5 Crohn's disease3,5

Chronic pouchitis2 Traveler's diarrhea3, Ulcerative colitis3

Ulcerative colitis2 Episodic diarrhea Pouchitis3

Intestinal infections Acute diarrhea3

Relapsing Clostridium difficile4 Antibiotic-associated diarrhea4

'Adapted from Sartor, 2005

2Prevention of relapse

^Treatment

4Prevention

5Postoperative prevention

For example, based on a review of the literature on the effect of probiotic bacteria on diarrheal disease, serum cholesterol, the immune system, and cancer prevention, the only consistent finding was a positive effect of Lactobacillus GG as a treatment against rotavirus intestinal infections (de Roos and Katan, 2000).This result was supported by a meta-analysis that also concluded that Lactobacillus therapy could be used safely and effectively to treat diarrheal disease in children (Van Niel et al., 2002).

Box 4β€”5. Sorting Through the Pros and Cons of Probiotics (Continued)

Table B. Probiotics: recommendations according to evidence-based medicine1,2.

Recommendation Evidence

Grade

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