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INTRODUCTION

Nearly all of the immune system components in the human body are located within the gastrointestinal (GI) system.¹ The importance of gut microbiota in GI and other disesases is increasingly accepted by health care professionals (HCPs) and, as a result, probiotics are increasingly recommended to patients.^2-4 Probiotics are defined as live microorganisms that confer a health benefit on the host when adminstered in adequate amounts.⁵ Probiotics are available in numerous types of products, including foods, drugs, and dietary supplements, but it is recommended that the term “probiotic” be reserved for live microbes that have demonstrated health benefits in controlled human studies. Table 1 clarifies terminology related to probiotics and associated products.⁵

Table 1: Clarification of Terminology5
Term	Definition	Examples*
Probiotic	Live organisms that provide therapeutic or preventative benefit for the host	Saccharomyces boulardii Bifidobacterium spp. Lactobacillus spp.
Prebiotic	Dietary substances that nurture a selected group of microorganisms living in the gut by favoring the growth of beneficial bacteria over that of harmful ones; typically nonstarch polysaccharides that are poorly digested by human enzymes	Oligofructose Inulin Galacto-oligosaccharides Lactulose
Synbiotics	Combinations of prebiotics and probiotics that exert the respective effects of both	Bifidobacterium spp. Fructo-oligosaccharides Lactobacillus rhamnosus GG
*Not an all-inclusive list of respective examples.

Lactobacillus, Bifidobacterium, and numerous other bacteria, fungi, and parasites are included in the “normal flora” of the GI tract.⁶ Likewise, Bifidobacterium species and Lactobacillus species, which are both lactic acid-producing bacteria, are 2 of the most commonly available probiotics. The nonpathogenic strain of yeast, Saccharomyces boulardii, is another example of a probiotic. Lactobacillus species were historically utilized to preserve food by fermentation. (A characteristic taste profile emerges through food fermentation, and food fermentation also prevents contamination by potential pathogens by lowering the pH of the food.) These bacteria now serve a dual function by also imparting health benefits.⁵

Intestinal microflora can be altererd by 1 of 4 mechanisms: administration of antibiotics, administration of prebiotics, administration of probiotics, or fecal transplant. Often, HCPs utilize probiotics to maintain or restore gut microecology during or after antibiotic treatment. Multiple hypothesized mechanisms exist to support their use, including competition for receptors, competition for nutrients, inhibition of epithelial and mucosal adherence of pathogens, introduction of lower colonic pH that favors the growth of nonpathogenic species of bacteria, stimulation of immunity, and production of antimicrobial substances.⁷ Probiotics induce protective cytokines, including interleukin-10 and transforming growth factor beta, and suppress proinflammatory cytokines, such as tumor necrosis factor, in the GI mucosa.⁸ While the exact mechanism of action of probiotics remains unclear, it is thought that probiotics may physicially or chemically prevent adhesion or colonization of pathogenic bacteria in the GI tract; this may, in turn, strengthen the immune response and recolonize the gut with beneficial microbes.⁹

Probiotics are considered safe in most healthy people. Some common side effects of probiotic use include flatulence and mild abdominal discomfort. Certain patients, such as those with compromised immune systems, should be advised not to use probiotics: patients who are immunocompromised are more susceptible to infections, including sepsis and Lactobacillus bacteremia.¹⁰ In addition to infections, other rare side effects of probiotic use include deleterious metabolic activities (e.g., deconjugation and dehydroxylation of bile salts, which can result in diarrhea and intestinal lesions), excessive immune stimulation, and gene transfer.¹¹

PROBIOTIC PRODUCT AVAILABILITY

Probiotics are identified by genus, species, and an alphanumeric designation. For example, for the probiotic Bifidobacterium lactis DN-173 010, Bifidobacterium denotes the genus, lactis denotes the species, and DN-173 010 designates the strain. Table 2 provides a list of the probiotics in select commercially available products.

Table 2: Examples of Commercially Available Probiotic Products
Product*	Probiotic(s)
Activia yogurt12	Bifidobacterium lactis DN-173 010
Align13	Bifidobacterium infantis 35624
Bio-K+14	Lactobacillus acidophilus CL1285 Lactobacillus casei LBC80R Lactobacillus rhamnosus CLR2
BioGaia15	Lactobacillus reuteri DSM 17938
Culturelle16	Lactobacillus rhamnosus GG Inulin
DanActive17	Lactobacillus acidophilus LA-5 Lactobacillus acidophilus NCFM Lactobacillus casei DN-114 001
Florajen18	Lactobacillus acidophilus
Florajen 319	Lactobacillus acidophilus Bifidobacterium lactis Bifidobacterium longum
Floranex20	Lactobacillus acidophilus Lactobacillus bulgaricus
Florastor21	Saccharomyces boulardii
Kefir22	Lactobacillus lactis Lactobacillus rhamnosus Lactobacillus plantarum Lactobacillus casei Lactobacillus acidophilus Lactobacillus reuteri Leuconostoc cremoris Streptococcus diacetylactis Saccharomyces florentinus Bifidobacterium longum Bifidobacterium breve Bifidobacterium lactis
Mutaflor23	Escherichia coli Nissle 1917
Phillips Colon Health24	Lactobacillus acidophilus Bifidobacterium bifidum Bifidobacterium longum
RepHresh Pro-B25	Lactobacillus rhamnosus GR-1 Lactobacillus reuteri RC-1461
VSL#3, VSL#3 DS26	Bifidobacterium breve Bifidobacterium longum Bifidobacterium infantis Lactobacillus acidophilus Lactobacillus plantarum Lactobacillus paracasei Lactobacillus bulgaricus Streptococcus thermophilus
*Not an all-inclusive list of products available on the market.

RECOGNITION AND ACCEPTANCE OF PROBIOTICS

In 2012, 1.6% of American adults (3.9 million people) reported using probiotics, which was 4 times higher than the rate of use in 2007.²⁷ The use of probiotics will likely continue to increase, so it is crucial that HCPs make evidence-based recommendations for their patients about probiotics. This underscores the need for effective communication among HCPs about probiotics to ensure optimal care for their patients.

Need for public and health professional education about probiotics

The efficacy of a single probiotic product cannot be extrapolated to other products. Further, there is no generic equivalency among probiotic products. If a patient presents for a probiotic recommendation, the HCP should recommend the specific strain(s) and product(s) that were studied in clinical trials for the respective disease state. Currently, no clinically meaningful head-to-head clinical trials have been conducted among different products.

As medication experts, pharmacists should consider several factors when recommending a probiotic product: duration of treatment, use in special populations, food allergies or lactose intolerance, and drug interactions. For example, pharmacists should read the label carefully to ensure appropriate selection of a probiotic without potentially inappropriate fillers. Species such as Streptococcus thermophiles and Lactobacillus delbrueckii subsp. bulgaricus have been demonstrated to improve lactose intolerance symptoms, but some probiotics products may contain lactose and cause GI irritation for people with lactose intolerance. ⁵ Additionally, some products may contain ingredients that can interact with other drugs. For example, Cuturelle Pro-Well 3-in-1 contains fish oil and vitamin C, which may interact with other prescription or over-the-counter medications a patient is taking.²⁸

Colony-forming units (CFUs) quantify the number of viable bacteria in a sample or product. The recommended daily intake for probiotics ranges from 1 billion CFUs to more than 100 billion CFUs per day.⁵ A typical dose may be written as 1 X 10⁹ CFUs. While this notation on product labeling can be confusing for people to interpret, it creates an optimal situation for pharmacists to help educate patients and make positive interventions.

HEALTH AND MEDICAL APPLICATIONS OF PROBIOTICS

In addition to GI diseases, probiotics are being used for the treatment and prevention of numerous other conditions. In the United States (U.S.), several professional organizations and medical associations have published 3 primary sets of guidelines regarding probiotic use, and, internationally, the World Gastroenterology Organisation (WGO) developed global guidelines for the use of probiotics and prebiotics.^5,29-31 The WGO is composed of individuals from more than 15 countries; the guidelines published by this group, which were updated in February 2017, clearly define the available evidence and clinical applications for probiotic use within each disease state.⁵ The American Association of Clinical Endocrinologists has a Nutrition Guidelines Taskforce that briefly summarized probiotic use and indications, especially those that are commonly encountered in the treatment of endocrinology and metabolism disorders, in the organization’s recent guidelines.²⁹ Additionally, in 2015, participants from the 4^th Triennial Yale/Harvard Workshop on Probiotic Recommendations offered a consensus opinion regarding probiotic use in several diseases in adults and children.³⁰ The American Academy of Pediatrics Committee on Nutrition developed a clinical report that reviewed the available health benefits of probiotics in children.³¹ Table 3 summarizes recent data on probiotic use in GI diseases, and Table 4 addresses non-GI disorders and conditions.

Table 3: Review of Data of Probiotics in Gastrointestinal Diseases
Disease state/condition	Study title	Probiotic regimen(s) studied	Conclusions
Antibiotic-associated diarrhea	Probiotics for prevention and treatment of antibiotic associated diarrhea: a systematic review and meta-analysis32	Lactobacillus Bifidobacterium Saccharomyces Streptococcus Enterococcus Bacillus	May reduce the duration of diarrhea by approximately 1 day, but the effect is strain- and dose-dependent; more research is needed to determine which probiotics are associated with the greatest efficacy; NNT = 12
Antibiotic-associated diarrhea	Probiotic VSL#3 prevents antibiotic-associated diarrhoea in a double-blind, randomized, placebo-controlled clinical trial33	VSL#3* twice daily	VSL#3 might reduce the incidence of antibiotic-associated diarrhea; NNT = 9
Clostridium difficile-associated diarrhea	Probiotics are effective at preventing Clostridium difficile-associated diarrhea: a systematic review and meta-analysis34	Lactobacillus Saccharomyces "A mixture of probiotics"	Patients interested in trying a probiotic should consider one with preliminary evidence, such as Saccharomyces boulardii (Florastor, others) or Lactobacillus (Culturelle, Bio-K+, others); more research is needed to determine which probiotics are associated with the greatest efficacy; NNT = 29
Clostridium difficile-associated diarrhea	Timely use of probiotics in hospitalized adults prevents Clostridium difficile infection: a systematic review with meta-regression analysis35	Saccharomyces Lactobacillus Lactobacillus in combination with another species	Probiotics administered close to the first dose of antibiotic reduces the risk of Clostridium difficile-associated diarrhea by more than 50% in hospitalized adults; NNT = 43
Clostridium difficile-associated diarrhea	Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children36	Any strain, any dose that studied probiotics for prevention of Clostridium difficile-associated diarrhea	Short-term use of probiotics has moderate evidence of benefit; may decrease the risk of diarrhea by 64%; NNT = 29
Irritable bowel syndrome	Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: systematic review and meta-analysis37	Lactobacillus Bifidobacterium Escherichia  Streptococcus	Probiotics exhibited beneficial effects on global irritable bowel syndrome, abdominal pain, bloating, and flatulence scores; the strains and species that are most beneficial remain unclear; NNT = 7
Constipation	The effect of probiotics on functional constipation in adults: a systematic review and meta-analysis of randomized controlled trials38	Bifidobacterium lactis Lactobacillus casei Shirota Escherichia coli Nissle Lactobacillus reuteri Lactobacillus paracasei Bifidobacterium breve  Lactobacillus plantarum	Probiotics improved stool frequency, whole gut transit time, bloating, incomplete evacuation, and hard stools
Ulcerative colitis	Effect of probiotics on inducing remission and maintaining therapy in ulcerative colitis, Crohn's disease, and pouchitis: meta-analysis of randomized controlled trials39	VSL#3*	Probiotic administration is associated with an additional benefit for inducing remission in ulcerative colitis; probiotics can provide similar effects to mesalazine in the remission of ulcerative colitis with fewer side effects
Pouchitis	Treatment and prevention of pouchitis after ileal pouch-anal anastomosis for chronic ulcerative colitis40	VSL#3*	VSL#3 may increase maintenance of remission and prevention of pouchitis compared to placebo or no treatment
Helicobacter pylori infection	Treating bugs with bugs: the role of probiotics as adjunctive therapy for Helicobacter pylori41	Lactobacillus spp. Saccharomyces spp. Bifidobacterium spp. Bacillus clausii	Probiotics may reduce adverse effects and increase tolerability of Helicobacter pylori eradication regimens
Abbreviations: NNT = number needed to treat. *VSL#3 contains several probiotics in a concentration of 450 billion live bacteria per sachet: Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasei, Lactobacillus delbrueckii subsp. bulgaricus, and Streptococcus thermophilus.

Probiotics in GI diseases

Probiotic use for GI diseases is fairly common, especially for maintaining gut flora, regularity, and general immunomodulating effects. Probiotics can increase healthy microorganisms in the gut, but more research is needed to better define probiotic efficacy, safety, and optimal dosing.

Probiotics should be considered as a treatment option in patients with certain GI disorders, though therapy with probiotics will not be effective for everyone. For example, according to a study of antibiotic-associated diarrhea, 12 patients need to be treated with a probiotic to prevent 1 case of diarrhea.³² According to another study, 1 case of Clostridium difficile-associated diarrhea could be prevented by treating 29 patients with a probiotic.³⁶ Some evidence suggests that the probiotic combination VSL#3 can induce remission in up to 53% of patients with ulcerative colitis who did not respond to initial treatment.³⁹ There is also evidence that supports utilizing VSL#3 to treat chronic pouchitis.⁴⁰ Little research has been conducted regarding probiotic use in Crohn’s disease. For patients with these disease states, HCPs must consider which probiotic regimen is associated with the most studied data to make strong, evidence-based recommendations.

Probiotics in non-GI conditions

Recently, data have emerged regarding the use of probiotics for non-GI diseases and conditions, such as vaginal yeast infections and eczema. Currently, there is no data to support probiotic use in asthma therapy, though this disease is garnering much attention related to probiotic use.

Table 4: Review of Data of Probiotics in Non-gastrointestinal Diseases and Conditions
Disease state/condition	Study title	Probiotic regimen(s) studied	Conclusions
Respiratory illness	Probiotics for preventing acute upper respiratory tract infections42	Actimel with Lactobacillus paracasei (Lactobacillus casei), Streptococcus thermophilus, and Lactobacillus bulgaricus Lactobacillus plantarum HEAL 9 plus Lactobacillus paracasei 8700:2 Lactobacillus rhamnosus GG Lactobacillus rhamnosus plus Bifidobacterium lactis Bb-12 Lactobacillus acidophilus plus Bifidobacterium bifidum Lactobacillus acidophilus plus Lactobacillus casei	Probiotics are better than placebo for reducing acute upper respiratory tract infections and the duration of an episode; the quality of evidence is low
Atopic dermatitis	Probiotics for the prevention of allergy: a systematic review and meta-analysis of randomized controlled trials43	Lactobacillus  and/or  Bifidobacterium	Probiotics used by women who are pregnant or breast feeding and/or given to infants may reduce the risk of eczema in infants; the quality of evidence is low
Urinary tract infection	Lactobacilli vs antibiotics to prevent urinary tract infections: a randomized, double-blind, noninferiority trial in postmenopausal women44	Lactobacillus	Probiotics are not as effective as antibiotics for preventing recurrent urinary tract infections
Bacterial vaginosis	Probiotics for the treatment of bacterial vaginosis45	Lactobacillus acidophilus Lactobacillus rhamnosus  Lactobacillus reuteri	Women with bacterial vaginosis tend to have less Lactobacillus and more gram-negative and other bacteria than women without vaginosis; while antibiotics have strong evidence of efficacy, women could consider using probiotics in combination with antibiotics (e.g., RepHresh, Pro-B)

PROBIOTIC SELECTION

Health benefits of probiotics have been demonstrated, but the effects described can only be attributed to the strain(s) tested and not all probiotics or even the species of bacteria.⁵ Several factors must be considered when helping a patient select a probiotic product, including the strain, specificity, and efficacy; methods of growth, harvest, and storage; bacterial cell counts; and the bacteria’s ability to survive to the intestines.

Influence of bacterial strain, specificity, and efficacy

Studies of a specific strain of probiotic must be conducted to ensure that strain specificity and efficacy are appropriate. Results of review articles cannot be used to support the health effects of untested strains. Additionally, the efficacy of a probiotic is at the specific dosage that was studied; health effects may not be achieved at lower dosages. There are no specific doses that apply to all probiotics because the dose varies so greatly depending on the strain and specific product. For example, the efficacy of Bifidobacterium infantis 35264 has been documented at 10⁸ CFU/day; for comparison, the recommended dose of VSL#3 is 1.8 x 10¹² CFU/day. This represents a 4-log difference, which is important since probiotics are may die during the storage of the product.^44,46

Probiotics are most commonly available in dairy products or probiotic-fortified foods, but probiotics are also available in freeze-dried forms including tablets, capsules, and sachets. Probiotics should be maintained in the original containers (or blister packs) and be discarded at the expiration date listed. Probiotics have an effective bacterial level until the “best by” date listed on the package.^44,46

Bacterial cell counts

An important component of probiotic effectiveness is the bacteria’s ability to reach and attach to the gut epithelium.⁵ For maximum effectiveness, the probiotic formulation must have a high bacterial count (i.e., a high number of viable bacteria) and must reach the active site of the colon (Table 5).

Table 5: Probiotic Products, Doses, and Uses Evaluated in Clinical Trials
Probiotic product*	Contents (dose)	Promoted use(s)	Clinical trials/studies
Align	Bifidobacterium infantis 35624 (1 billion CFUs)	Fortifies digestive health and balance13	At least 20 published clinical trials including double-blind, placebo-controlled studies
Bio-K+	Lactobacillus acidophilus CL1285 (12.5 billion CFUs) Lactobacillus casei LBC80R (25 billion CFUs) Lactobacillus rhamnosus CLR2 (30 billion CFUs)	Reduces antibiotic- and Clostridium difficile-associated diarrhea14	At least 10 published clinical trials including double-blind, placebo-controlled studies
Culturelle	Lactobacillus rhamnosus GG (amount varies depending on specific product: Digestive Health = 10 billion active cultures + inulin 200 mg/capsule; Health & Wellness = 15 billion active cultures/capsule; Kids Packets or Chewables = 5 billion bacteria per packet or tablet)	Helps digestive system work better; reduces digestive upset; helps with diarrhea, gas, and bloating; supports immune system16	At least 20 published clinical trials including double-blind, placebo-controlled studies
Florastor	Saccharomyces boulardii lyo CNCM I-745 (250 mg/capsule)	Strengthens digestive balance and supports a healthy immune system; only probiotic that contains the yeast Saccharomyces boulardii lyo CNCM I-74521	At least 25 published trials, including double-blind, placebo-controlled studies
RepHresh Pro-B	Lactobacillus rhamnosus GR-1 (5 billion CFUs) Lactobacillus reuteri RC-14 (5 billion CFUs)	Vaginal health through balancing vaginal flora25	At least 10 published studies, including randomized, double-blind, placebo-controlled trials
VSL#3	Lactobacillus acidophilus Lactobacillus plantarum Lactobacillus paracasei Lactobacillus bulgaricus Bifidobacterium breve Bifidobacterium infantis Bifidobacterium longum Streptococcus thermophilus (amount varies depending on specific product: Regular packet = 450 billion live bacteria; Junior packet = 225 billion live bacteria; DS packet = 900 billion live bacteria)	Dietary management of irritable bowel syndrome, ulcerative colitis, and ileal pouch26	At least 170 published studies, including double-blind, placebo-controlled studies
Abbreviations: CFU = colony-forming units. *Not an all-inclusive list of probiotic products.

Ability of probiotic to survive passage through GI tract to colon

For a probiotic to be effective, it needs to colonize in the host’s intestine. Numerous factors affect the survival of ingested probiotics in the GI tract. Variability in the pH, length of acid exposure, and species and strains used in the product lead to differences in survival in the stomach. In one study, Lactobacillus acidophilus strains 2401, 2409, and 2415; Bifidobacterium longum strain 1941; and Bifidobacterium pseudolongum strain 20099 proved to withstand the varying conditions most consistently.⁴⁶ In the small intestine, bile salts can affect probiotic survival, and probiotics should be bile tolerant in order to survive. According to the same study, Bifidobacterium longum 1941, Bifidobacterium infantis 1912, Bifidobacterium pseudolongum 20099, and Lactobacillus acidophilus 2404 and 2415 most consistently survived in the small intestine.⁴⁶

PHARMACIST-PHYSICIAN COMMUNICATION ABOUT PROBIOTICS

Even HCPs who regularly recommend probiotics may not understand the distinctions between probiotic formulations, the importance of high bacterial counts, or the significance of bacterial strains used in the formulations. This lack of understanding highlights the improvements needed in communication among HCPs and between HCPs and patients.

Expanding communication and collaboration skills with physicians

According to the Harris Poll GI Issues Survey, only 10% of people stated that a health professional had advised them about which probiotic would be most suitable for a specific condition.⁴⁷ Pharmacists are ideally positioned to educate patients and follow-up on physician suggestions to help provide patients with evidence-based recommendations for probiotic use. For example, physicians often recommend probiotics along with an antibiotic: a pharmacist working in the community setting should ask follow-up questions to determine why a probiotic was recommended in order to select an appropriate product that considers the patient’s disease states and desired outcomes. After the encounter, the pharmacist should document the interaction and notify the physician and other members of the health care team to ensure a complete medication list. Collaborative activities like this could improve relationships among interprofessional teams.

Educating patients about probiotics

Patients have numerous products from which to choose, so purchasing a probiotic from the over-the- counter aisles can be overwhelming. Despite the more than 75 available probiotics and formulations, patients do not always ask questions or initiate a conversation with a pharmacist or HCP about probiotic selection. Importantly, not all probiotics are effective, and an HCP should help a patient choose a probiotic with demonstrated effectiveness.

For patients to receive the most benefit from a probiotic, it is important that they are properly counseled and educated about how to dose and administer the product. If an HCP is going to recommend probiotic therapy, he or she should understand administration guidelines and take time to educate the patient. Specifically, patient education should include the concept of probiotics being “good bacteria,” the timing of probiotics according to the indication, the dosing of probiotics according to the product’s labeling, proper storage of the probiotic, and the fact that probiotics are not regulated by the U.S. Food and Drug Administration (FDA). Of course, patients should also understand their specific conditions. Overall, the decision to initiate probiotic therapy should take into account a patient’s disease state and preferences, cost, available evidence for the recommended probiotic, and complexity of the regimen.

DIETARY SUPPLEMENTS VERSUS MEDICAL FOODS

Probiotics are available without a prescription, which often leads people to believe that they are less effective than prescription-only products. Additionally, because probiotics are often included in the complementary and alternative medicine category, some may feel skeptical of the validity of the products.⁴⁸ Probiotics are composed of many living microogranisms; as such, probiotics are not considered a one-size-fits-all treatment. Therefore, how a probiotic product is used will help determine the category to which it is assigned. In turn, this will detemine the regulatory status of the probiotic product. The Federal Food, Drug, and Cosmetic Act established the legal framework with which the FDA operates in regulating food, drugs, and other products.⁴⁹ Depending on the claims made on a product’s behalf or the risks a product presents, some products require more concern, attention, substantiation, and vetting than others. A probiotic product is placed into 1 of 4 regulatory categories on the basis of the probiotic and its intended use: (1) food or food ingredient, (2) medical food, (3) drug, or (4) biological product (Table 6).⁵⁰

Table 6: Regulatory Categories of Probiotic Products50
Classification	Intended use	Regulatory consequences
Food	Not categorized by "intended use"; categorized only by "use"	Regulated as a food additive or as a GRAS food ingredient; subject to regulation under the FDA's controls that govern food adulteration
Medical food	Intended for enteral use in the "dietary management of a disease or condition for which distinctive nutritional requirements have been established by medical evaluation"; formulated to be administered "under the supervision of a physician"	No premarket clearance requirements apply unless categorized as food; additive and GRAS considerations may apply with respect to ingredients; claims must (1) focus on the dietary management of a disease, (2) be conditioned on appropriate medical supervision, and (3) address a distinct nutritional need
Dietary supplement	Intended to "supplement the diet"; is or contains a "dietary ingredient"; is "intended for ingestion"; is not in "conventional" food form	If a probiotic meets the definition for a dietary supplement, a manufacturer may place the probiotic on the market without premarket approval and can make claims regarding the effect product has on the structure/function of the body
Drug	Intended for the cure, mitigation, treatment, diagnosis, or prevention of disease	A probiotic intended for use as a "drug" is also a "biological product" if it meets the definition of a "new drug" (section 201(p) of the Food, Drug, and Cosmetic Act); FDA will require an approved Biologics License Application and an Investigational New Drug Application to determine safety and efficacy
Biological product	Contains a virus, serum, or toxin "applicable" to the prevention, treatment, or cure of a disease or condition
Abbreviations: FDA = U.S. Food and Drug Administration; GRAS = generally recognized as safe.

There is no legal requirement to demonstrate safety, purity, or potency before marketing probiotics.¹⁰ As a result, a probiotic cannot be labeled or marketed as a product that is intended to treat or prevent a disease; structure and/or function claims are commonly used in the labeling and marketing of probiotics.

Prescription and nonprescription probiotic formulations

The majority of probiotic formulations are over-the-counter products that can be purchased without a prescription at a pharmacy, grocery store, or convenience store. One probiotic, VSL#3 DS, requires a prescription: the prescription requirement was established by the manufacturer and is not a requirement of the FDA. The manufacturer, Sigma-Tau Healthscience, believes that obtaining a prescription will help patients adhere to proper use and avoid confusion and infrequent follow-up with HCPs.²⁶

Administration and distribution of medical foods

Since medical foods are not drugs, they are not subject to any regulatory requirements.⁴⁶ Medical foods may not bear the “Rx only” symbol and they do not have a National Drug Code number. The FDA does not require that medical foods be available by written or oral prescription. Also, the requirement for use “under the supervision of a physician” is included in the instructions for use of medical foods. This requirement can be simply defined as a patient seeing the physician on a regular, recurring basis. VSL#3 is considered a probiotic and a medical food.²⁶

Both medical foods and dietary supplements are intended for oral or enteral administration.³⁷ Medical foods have nutritional requirements that are based on recognized scientific principles and medical foods are intended to be used only for the specific dietary management of a medical condition or disease that cannot be managed by modifying the normal diet alone.²⁶ In addition, medical foods have ingredients that should be generally recognized as safe under their respective intended uses. Still, medical foods should only be used under medical supervision.²⁶

CONCLUSION

Probiotic therapy may be beneficial for people with GI diseases, as well as other non-GI conditions. Probiotic use has increased at least 4-fold in recent years, which reinforces the importance that HCPs should place on personalizing probiotic use for an individual’s needs. Probiotics help balance the gut microbiota and normalize bodily functions; however, not all probiotics are created equal. The activities and efficacies of probiotics vary according to bacterial strains and differences have been confirmed in studies conducted on individual products. For this reason, HCPs cannot extrapolate a single probiotic to have similar efficacy to another, even in the same disease state. It is essential that the pharmacist and health care team work together to provide evidence-based recommendations to patients to ensure positive outcomes.

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