I would keep an eye out for this systematic review titled
Safety of Probiotics Used to Reduce Risk and Prevent or Treat Disease by an AHRQ Evidence-based Practice Center to be completed and made available online soon.
Key questions that will guide the literature review and be answered with regard to the evidence base and strength of the evidence include:
Note: Questions #1 and #2 relate to six taxonomic groups (Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, and Bacillus).
1. What is the evidence that the active (e.g., live or viable) and lyophilized forms of probiotics (Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, and Bacillus) as single ingredients or in combination with other probiotics or prebiotics in all delivery vehicles (and formulations) when used to cure, treat, mitigate or prevent a disease or reduce disease risk are safe in the short-term? Long-term?
a. What safety parameters are collected in clinical studies (Phases I-IV)?
b. What harms are reported in clinical studies (Phases I-IV)?
c. What harms are reported in case reports?
d. What safety parameters are collected in population surveillance studies and other observational studies, and do these include only standard clinical safety parameters (e.g., standard blood chemistry profiles) or also expanded laboratory or clinical testing unique to the use of probiotics?
e. What harms are reported in population surveillance studies and other observational studies?
f. What harms are reported in human mechanistic studies?
g. Do the studies describe an antibiotic therapy designed to treat unintended pathology caused by the administered organism?
h. Do the studies describe methods for recovery of the administered organism from either the gastrointestinal tract or serum?
2. What are characteristics and associations of the reported harms in Question 1?
a. What interactions between probiotics and medications are reported?
b. What harms related to acquired antibiotic resistance and/or transferability are reported?
c. What is the nature of harms (e.g., toxicogenic, immunologic, hematologic, deleterious physiologic or metabolic activity, allergic, blood infections, hematocytometric values, liver and renal function enterotoxin, production, proteases, or opportunistic infection, etc.), and do these include only standard harms or also harms that might be uniquely applicable to the use of a probiotic?
3. What is the evidence that harms of Lactobacillus, Bifidobacterium, Saccharomyces, and Streptococcus identified in Question #1 differ by product and delivery characteristics?
a. What is the scientific evidence that harms differ by delivery vehicle including excipients or novel delivery vehicles?
b. What is the scientific evidence that harms differ by genus, species, and strain (including intraspecies strain variations)?
c. What is the scientific evidence that harms differ between active and lyophilized forms of probiotics?
d. Does harm differ by products containing a single probiotic vs. a mixture of probiotics?
e. Does harm differ by products containing only probiotics and those containing a mixture of probiotics and prebiotics?
4. How do the harms of Lactobacillus, Bifidobacterium, Saccharomyces, and Streptococcus vary based on (a) dose (cfu); (b) timing; (c) mode of administration (e.g., catheter); (d) age (all ages, including infants), gender, ethnicity, disease or immunologic status of the patient; (e) relationship to efficacy?
a. Is there a threshold or dose-response relationship between probiotics and harm? Does the duration of intervention relate to harm?
Note: Dose (cfu) of active microorganisms needs to be verified. When viable (active) probiotics are added to a vehicle, their viability and/or dose may be compromised. Literature reports should include verification of dose if available. If not, the Evidence-Based Practice Center may try to verify the dose with investigators.
b. Is there a relationship between time of onset of harm and time of probiotic administration (e.g., prior to onset of disease under study, after disease onset)? How does time of exposure affect harm? Is harm sustained after the intervention or exposure stops?
c. Does the route of administration (e.g., orally, jejunostomy tube, central venous catheter) relate to harm?
d. How does harm relate to subpopulations, including different age groups (specifically including neonates and infants under age 24 months), men and women, ethnic/race subgroups, or health status (healthy to high risk) individuals?
e. Do randomized controlled studies that report harm show efficacy or no efficacy?
5. How often does harm associated with Lactobacillus, Bifidobacterium, Saccharomyces, and Streptococcus lead to hospital admission or lengthened hospitalization?
6. How does harm associated with Lactobacillus, Bifidobacterium, Saccharomyces, and Streptococcus relate to use of concomitant antibiotics, confounding diet therapies, corticosteroid use, immune suppressants, or other potential confounders?
http://www.ahrq.gov/clinic/tp/probiotictp.htm
