EARN 3 CPD PROBIOTICS POINTS ONLINE Probiotics – EvALUATING THE BENEFITS Introduction Interest in probiotics has grown over the past two decades, particularly as a result of recent research investigating the role gut microbiota play in the development of chronic diseases. Clinical update KEY MESSAGES report by • The clinical use of probiotics has benefited from recent quality randomised clinical trials (RCTs). • Cochrane review supports the beneficial effects of specific probiotic strains in the treatment of antibiotic-associated diarrhoea in children and adults. • Prevention of necrotising enterocolitis (NEC) with probiotics in preterm infants is widely accepted, with input from with supportive evidence from South African studies in HIV-exposed premature infants. Prof Leon M.T. Dicks • Probiotics show potential in the prevention of chronic disorders (obesity, metabolic disorders, Professor of Microbiology non-alcoholic fatty liver disease) Department • A South African probiotic developed at the University of Stellenbosch has passed the key hurdles of Stellenbosch University safety and efficacy studies in both in vitro and in vivo systems. Further clinical studies are warranted. Faculty of Health Sciences Probiotics are defined as ‘live micro- reflected in the fact that many of today’s organisms that beneficially affect the ‘functional foods’ contain probiotics. host by improving microbial balance’.1 In pharmaceutical medicine, probiotics A recent WHO Food and Agricultural are classified as ‘nutraceuticals’ and offer Organisation definition has redefined this a more concentrated form of the probi- to include the need for adequate levels otic or probiotic combination. of probiotics to be administered. This Initial trials of probiotics suffered from definition states that ‘probiotics are live many shortcomings, similar to those of organisms which, when administered in dietary supplements. In the last decade, adequate amounts, confer health benefits however, a large number of scientific to the host.’ studies have addressed the mechanism of Probiotics have been shown to provide action of probiotic strains. Increasingly, beneficial effects by replenishing natural clinical trials are undertaken to support gastrointestinal flora. In African culture, ‘health claims’ and to provide a better fermented milk is regarded as having understanding of which probiotics are health benefits for the gastrointestinal beneficial and to define their evidence- tract. The popularity of probiotics is based use. This article was made possible by an unrestricted educational grant from Cipla, which had no control over content. APRIL 2016 1 PROBIOTICS Major micro-organisms Table 1. Micro-organisms considered to be considered to be probiotics probiotics Lactobacillus Bifidobacterium Lactic acid bacteria are the major species species group of bacteria suitable for use as L. acidophilus B. adolescentis probiotics. They are Gram-positive and L. casei B. animalis catalase-negative, and produce lactic L. crispatus B. bifidum acid as the main end product from the L. gallinarum (Mainly B. breve fermentation of carbohydrates. The most used in animals) important genera are Lactobacillus and L. gasseri B. infantis Bifidobacterium, which are used in food B. lactis (Recently reclassified L. johnsonii products and nutraceuticals. Enterococcus as B. animalis subsp. lactis) is also an important lactic acid bacterium, L. paracasei B. longum which is often used in combination with L. plantarum either Lactobacillus or Bifidobacterium. Table 1 provides a list of species used and L. reuteri cited in clinical research.2 L. rhamnosus Essential probiotic properties “The most Probiotics need to be able to withstand the probiotic can compete even more the harsh gastric environment to reach successfully with pathogenic bacteria) important probiotic the intestine and adhere to the mucosal 4. Bile salt hydrolase activity genera are and epithelial surfaces. In vitro tests are 5. Resistance to certain antibiotics, so used to determine the following desirable that the probiotic is able to restore the Lactobacillus and properties: microbial balance and prevent antibi- Bifidobacterium” 1. Acid and bile tolerance; essential for otic side-effects oral administration 6. Quantity of viable micro-organisms, 2. Adhesion to mucosal and epithelial although not precisely defined, should surfaces to compete with and exclude reach a minimum total of 108 – 109 pathogenic bacteria from the receptor colony forming units (CFUs). Viability 3. Production of antimicrobial activity should also be maintained under nor- against pathogenic bacteria (so that mal storage conditions. Mechanisms of action Probiotics have various mechanisms of is considerable evidence that probiotics action. These include the production influence the acquired and innate immune of bacteriocins (antibacterial peptides) response by inducing phagocytosis and and short-chain fatty acids, lowering of IgA secretion, modifying helper T-cell gut pH, stimulation of mucosal barrier response and the release of cytokines in a function and immunomodulation. There strain-specific manner.3 Evaluating the benefits of probiotics in the perinatal period and early childhood Maternal probiotic supplements A recent double-blind randomised clini- Bifidobacterium BL999, also Lactobacillus cal trial (RCT) of probiotic supplementa- GG.5 A recent Cochrane review6 from the tion during pregnancy (two months prior Department of Clinical Epidemiology to delivery) and breastfeeding found the and Biostatistics, McMaster University, Earn 3 CPD points at supplementation safe and effective in Canada, conducted a meta-analysis of 29 www.denovomedica.com reducing the risk of eczema in infants RCTs and supported this outcome, but Click on ‘Accredited of allergic mothers positive for skin- pointed out that the certainty of the evi- 4 CPD modules’. prick tests. The strains used in this trial dence for various probiotic strains is still were Lactobacillus rhamnosus LPR and low. 2 APRIL 2016 PROBIOTICS “Probiotic Probiotics of Lactobacillus and to transfer into breast milk.7 Ingestion of supplementation Bifidobacterium species were evaluated viable probiotic bacteria (Bifidobacterium to be safe when administered to healthy and Streptococcus thermophiles) in infant reduces the risk of pregnant women in the last trimester of formula over a six-month period has also eczema in infants at pregnancy. As probiotics are rarely sys- been shown to be well-tolerated, safe and 8 high-risk” temically absorbed, they are not expected conducive to adequate growth. Prevention of antibiotic-associated diarrhoea (AAD) in otherwise healthy children A recent Cochrane review of 23 studies to determine the changes in intestinal using a diverse selection of probiotics (bifi- microbiota composition after antibi- dobacteria, lactobacilli, lactococci, strep- otic treatment in early life.10 These types tococci, Clostridium butyricum, Bacillus of studies will become more frequent as species) has shown a protective effect of gene analysis of microbiota is applied to probiotics in preventing AAD with a num- clinical settings and will provide a further ber-needed-to-treat (NNT) of 10.9 The basis for probiotic intervention. report singled out a benefit of Lactobacillus The long-term safety of probiotics rhamnosus / Saccharomyces boulardii and given as nutraceuticals from birth to noted that probiotics should not be used six years of age (Bifidobacterium and in severely debilitated or immune-compro- Lactococcus) has been assessed in terms of mised children. the development of gut microbiota11 and A large study was recently concluded, found not to result in lasting differences but results are not yet available. It aimed to the composition thereof. Prevention of Clostridium difficile-associated diarrhoea in children (and adults) “Cochrane review A meta-analysis of 23 randomised tri- nausea, fever, flatulence and taste distur- shows protective als suggests that when probiotics are bance) were also reduced by concomitant effect of probiotics administered with antibiotics, they reduce probiotic administration.12 The probiotic the risk of Clostridium difficile-associ- species most used were Lactobacillus, on antibiotic- ated diarrhoea by 64%. The most com- Bifidobacterium, Saccharomyces and a associated diarrhea” mon side-effects (abdominal cramping, combination of these strains. Prevention of necrotising enterocolitis (NEC) in preterm infants The American Pediatric Surgical Assoc- probiotic therapy consisting of 1 × iation supports the use of prophylactic 109 colony forming units (CFUs) of probiotics in preterm infants weighing Lactobacillus GG and Bifidobacterium less than 2.5 kg to reduce the incidence infantis in HIV-exposed premature infants of NEC, as well as the use of breast milk showed that this combination safely rather than formula where possible.13 reduced the incidence and severity of A South African study using a daily NEC in these infants at risk of HIV.14 Probiotics in adults Irritable bowel syndrome (IBS) Several trials and meta-analyses have it may be a post-inflammatory and stress- shown that probiotics (particularly lacto- related condition. Probiotics appear to be bacilli and bifidobacteria) reduce abdom- a useful option in terms of both efficacy inal pain and symptom severity in IBS.15 and safety, but until the pathophysiology Earn 3 CPD points at IBS is, however, a heterogeneous func- of the condition is clear, evidence of pro- www.denovomedica.com tional disorder, which is still incompletely