Insights Into the Pharmacist's Role in the Selection of a Clinically Proven Probiotic

This article was sponsored by i-Health, Inc.​​​​​

The microbiota is the community of microorganisms, including bacteria and fungi, that reside within and on the human body.^1,2 The largest of these communities is the gut microbiota, which is critical for a variety of functions, including metabolic processes, maintenance of gut barrier integrity, and vitamin synthesis.³ The epithelial barrier, which is exposed to a variety of substances and organisms, plays an important role in supporting appropriate immune responses.^3,4 The commensal microbiota plays a key role in maintaining the health of this barrier by competing with pathogenic bacteria, consuming nutrients, and releasing protective peptides, cytokines, and white blood cells. Adhesion to the epithelial barrier is believed to be an important aspect of this process.

Probiotics are live microorganisms that provide various health benefits, when administered in adequate amounts, including promoting the balance of intestinal microbiota, assisting digestion, and supporting the immune system by working with the endogenous microbiota.^3-5 (A GLOSSARY^2,3,6-9 is provided below that includes key terms related to probiotics.) The benefits of probiotics are strain-specific because of the varying abilities of each microorganism to survive acid and bile in the gastrointestinal (GI) tract, adhere to GI mucosa, and employ different mechanisms to exert their effects.⁵ Of the available probiotic strains, Lactobacillus rhamnosus GG (LGG^®) is the most studied, with more than 1000 scientific publications that include more than 200 clinical trials.⁴ LGG^® helps restore balance to the microbiota to support digestive and immune health.⁵

LGG^®: A CLINICALLY PROVEN EFFECTIVE STRAIN

Among the well-known features of LGG^® is its ability to adhere to epithelial cells. Electron micrographs have observed the presence of unique pili on LGG^®, which contribute to its superior capacity for adherence to intestinal cells resulting in a stable interaction.^9,10 Physiologically, LGG^® improves epithelial barrier function and exerts its effects by competing with pathogens for nutrients and binding sites. Moreover, LGG^® modulates select proinflammatory molecules, and directly releases antimicrobial substances.⁹

In vitro studies of LGG^® have demonstrated^9,11-13:

• acid and bile tolerance
• attachment to intestinal cells
• production of protective mucins
• improvement in intestinal barrier function
• secretion of antimicrobial compounds
• inhibition of pathogen growth
• proliferation of intestinal epithelial cells
• production of lactic acid, contributing to inhibitory effects of bacteria at appropriate pH levels in the intestines

Reduction in the Incidence of Antibiotic-Associated Diarrhea

Multiple clinical trials have demonstrated that supplementation with LGG^® helps to reduce the incidence and duration of diarrhea resulting from dysbiosis due to viral and bacterial intestinal infections and from the adverse effects (AEs) associated with the use of antibiotic therapy.^4,11 Three clinical studies demonstrated that taking 12 billion colony-forming units (CFUs) of LGG^® daily improved antibiotic treatment tolerability by reducing the incidence of diarrhea in adults when taken during triple drug therapy that included an antibiotic (

FIGURE 1

).^14-16

Children who take LGG^® during their treatment with an antibiotic are also less likely to experience antibiotic-associated diarrhea (AAD). In a study evaluating the efficacy of LGG^® in children aged between 6 months and 10 years with an acute infection who received a course of antibiotics (N = 188), the incidence of diarrhea, defined as the presence of 2 loose stools per day for at least 2 days, occurred in 26% of patients who received placebo and 8% of patients who received LGG^® (

FIGURE 2

).¹⁷ Moreover, for those who experienced diarrhea, the mean duration of symptoms was significantly shorter in patients who received LGG^® compared with placebo (4.7 days vs 5.9 days, respectively; P = .05).¹⁷

Culturelle^® Is Powered With LGG^®

Culturelle^® contains LGG^®, which survives the harsh conditions of the stomach and exerts its effect in the intestines to promote digestive health and wellness for patients of all ages.^14-16 The foundational strain in Culturelle^® balances the digestive system to help with occasional digestive complaints; helps support immune health; and helps reduce fussiness and crying associated with GI upset in infants.¹⁸ No serious AEs have been reported with the use of LGG^® in a wide range of clinical trials, even in extremely vulnerable populations, including pregnant women and low birthweight infants.⁹

PURITY AND POTENCY

For a probiotic to provide optimal outcomes, the microorganisms contained within must survive until time of consumption (or expiration). Culturelle^® probiotics are manufactured and packaged to prevent moisture, light, and air from compromising the probiotics and to ensure product viability and the stated number of CFUs in each dose through the expiration date, when stored as directed.

ROLE OF THE PHARMACIST

Patients of all ages may benefit from the use of probiotics to support immune and digestive health. Pharmacists are positioned to identify ideal candidates for probiotics during patient encounters. In addition to the benefits previously mentioned, results from multiple clinical trials have demonstrated the role of LGG^®, a clinically proven effective strain, in reducing the incidence of AAD in both adults and children.^14-17 Both children and adults who are taking an antibiotic may benefit from the use of Culturelle^®, a probiotic that contains LGG^®.

Pharmacists are challenged with the responsibility to remain current about available over-the-counter probiotics so they may make appropriate recommendations for specific patient populations. When recommending a probiotic, it is important to understand that not all strains are the same, and many benefits are strain-specific. Pharmacists, armed with the appropriate knowledge, can counsel patients on products with the strain or blends that have the desired clinically-proven benefit.

In addition to clinically supported benefits, there are several additional characteristics of a quality probiotic product. The label of a quality probiotic should always include the following⁶:

• Suggested dose or serving size consistent with scientific evidence.
• Quantity in CFUs through to the expiration date
• Names of the microbes including the genus, species, and strain for each microbe in the product
• Expiration date
• Proper storage instructions
• Company contact information

When recommending a probiotic¹⁹:

• Understand that not all strains are the same! Benefits are strain-specific, so choose a product with the clinically proven strain for the intended benefit.
• Select a probiotic that has clinical evidence for that strain (or blend) at the provided dose.
• Be cautious of:

• High CFU count; more isn’t better.
• Multistrain probiotic formulas. Most have no clinical evidence.

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

References

• Jandhyala SM, Talukdar R, Subramanyam C, Vuyyuru H, Sasikala M, Nageshwar Reddy D. Role of the normal gut microbiota. World J Gastroenterol. 2015;21(29):8787-8803. doi: 10.3748/wjg.v21.i29.8787.
• Quigley EM. Gut bacteria in health and disease. Gastroenterol Hepatol (N Y). 2013;9(9):560-569.
• Bull MJ, Plummer NT. Part 1: the human gut microbiome in health and disease. Integr Med (Encinitas). 2014;13(6):17-22.
• Lactobacillus rhamnosus GG: the ideal probiotic strain for adults. I-Health, Inc website. s3.amazonaws.com/culturelle2017-hcp/pdf/CRQP2030%20%20Culturelle_Adults%20Prof_Booklet%20Final-web.pdf. Accessed April 29, 2019.
• Thomas CM, Versalovic J. Probiotics-host communication: modulation of signaling pathways in the intestine. Gut Microbes. 2010;1(3):148-163. doi: 10.4161/gmic.1.3.11712.
• Probiotic checklist: making a smart selection. International Scientific Association for Probiotics and Prebiotics website. isappscience.org/isapp-releases-new-infographic/probiotic-checklist-infographic/. Published October 2, 2018. Accessed May 1, 2019.
• Sekirov I, Russell SL, Antunes LC, Finlay BB. Gut microbiota in health and disease. Physiol Rev. 2010;90(3):859-904. doi: 10.1152/physrev.00045.2009.
• World Gastroenterology Organisation global guidelines: probiotics and prebiotics. World Gastroenterology Organisation website. worldgastroenterology.org/guidelines/global-guidelines/probiotics-and-prebiotics/probiotics-and-prebiotics-english. Published February 2017. Accessed May 1, 2019.
• Segers ME, Lebeer S. Towards a better understanding of Lactobacillus rhamnosus GG—host interactions. Microb Cell Fact. 2014;13(Suppl 1):S7. doi: 10.1186/1475-2859-13-S1-S7.
• Tripathi P, Dupres V, Beaussart A, et al. Deciphering the nanometer-scale organization and assembly of Lactobacillus rhamnosus GG pili using atomic force microscopy. Langmuir. 2012;28(4):2211-2216. doi: 10.1021/la203834d.
• Gogineni VK, Morrow LE, Malesker MA. Probiotics: mechanisms of action and clinical applications. J Prob Health. 2013;1(1):1-11. doi: 10.4172/2329-8901.1000101.
• Yan F, Cao H, Cover TL, Whitehead R, Washington MK, Polk DB. Soluble proteins produced by probiotic bacteria regulate intestinal epithelial cell survival and growth. Gastroenterology. 2007;132(2):562-575. doi: 10.1053/j.gastro.2006.11.022.
• Silva M, Jacobus NV, Deneke C, Gorbach SL. Antimicrobial substance from a human Lactobacillus strain. Antimicrob Agents Chemother. 1987;31(8):1231-1233. doi: 10.1128/aac.31.8.1231.
• Armuzzi A, Cremonini F, Bartolozzi F, et al. The effect of oral administration of Lactobacillus GG on antibiotic-associated gastrointestinal side-effects during Helicobacter pylori eradication therapy. Aliment Pharmacol Ther. 2001;15(2):163-169.
• Armuzzi A, Cremonini F, Ojetti V, et al. Effect of Lactobacillus GG supplementation on antibiotic-associated gastrointestinal side effects during Helicobacter pylori eradication therapy: a pilot study. Digestion. 2001;63(1):1-7. doi: 10.1159/000051865.
• Cremonini F, Di Caro S, Covino M, et al. Effect of different probiotic preparations on anti-helicobacter pylori therapy-related side effects: a parallel group, triple blind, placebo-controlled study. Am J Gastroenterol. 2002;97(11):2744-2749. doi: 10.1111/j.1572-0241.2002.07063.x.
• Vanderhoof JA, Whitney DB, Antonson DL, Hanner TL, Lupo JV, Young RJ. Lactobacillus GG in the prevention of antibiotic-associated diarrhea in children. J Pediatr. 1999;135(5):564-568.
• Pärtty A, Luoto R, Kalliomäki M, Salminen S, Isolauri E. Effects of early prebiotic and probiotic supplementation on development of gut microbiota and fussing and crying in preterm infants: a randomized, double-blind, placebo-controlled trial. J Pediatr. 2013;163(5):1272-1277.e1-e2. doi: 10.1016/j.jpeds.2013.05.035.
• Probiotics: dispelling myths. International Scientific Association for Probiotics and Prebiotics website. isappscience.org/infographic-dispelling-myths/. Published January 21, 2018. Accessed June 25, 2019.