EARN 3 FREE CPD POINTS PROBIOTICS Leader in digital CPD for Southern African healthcare professionals Probiotics for gastrointestinal and related conditions Article reviewed by Introduction The progressive westernisation of diets and lifestyles of South Africans is likely to be associated with an increase in gastrointestinal conditions such as constipation, colorectal cancer, functional abdominal pain and irritable bowel syndrome (IBS). 1 The latter is a complex condition and its pathogenesis differs from individual to individual. It is characterised by recurrent abdominal pain associated with alterations in bowel habits. Modifications in the gut microbiota and immunomodulation are linked to IBS symptom development. Professor Leon MT Dicks Distinguished Professor in: Microbiology Industrial, Food and Medical Microbiology Antimicrobial Peptides Probiotic Lactic Acid Bacteria Department of Microbiology Stellenbosch University Key recommendations for clinical practice 2 Probiotic use reduces the risk of antibiotic-associated diarrhoea in children and adults Probiotic use may reduce the incidence of Clostridium difficile-associated diarrhoea Probiotic use significantly reduces the risk of hepatic encephalopathy Probiotic use increases remission rates in adults with ulcerative colitis Probiotic use improves abdominal pain and global IBS symptoms Probiotic use reduces the incidence of necrotising enterocolitis and mortality in preterm infants. This article was made possible by an unrestricted educational grant from Cipla, which had no control over content. APril 2018 I 1
Prevalence of IBS in South Africa A very recent study of work-related stress, burn-out and self-reported illness among some 8000 employees from various economic sectors in South Africa illustrates the growing prevalence of IBS among South Africans. The study included an equal number of black people (42%) and white people (42%) working in the financial, government and health sectors providing data that are relevant to our demographic situation. Fifty-five percent were women and 45% men; the majority were in the age group of 30-49 years. The incidence of self-reported health conditions is summarised in Table 1, indicating that IBS ranked third after hypercholesterolaemia and hypertension. 3 Burn-out and stress had a significant relationship with IBS. Table 1. Incidence of self-reported existing health conditions among a large South African employee cohort (n=7895) 3 Health condition Frequency Percentage (%) Cardiovascular conditions 181 2.3 Cholesterol 629 8.0 Depression 429 5.4 Diabetes 324 4.1 Hypertension 1026 13.0 IBS 527 6.7 Overview of probiotics and their function Major micro-organisms considered to be probiotics Lactic acid bacteria are the major group of bacteria suitable for use as probiotics. They are Gram-positive and catalase-negative, and produce lactic acid as the main end-product from the fermentation of carbohydrates. The most important genera are Lactobacillus and Bifidobacterium, which are used in food products and nutraceuticals. Enterococcus is also an important lactic acid bacterium, which is often used in combination with either Lactobacillus or Bifidobacterium. Table 2 provides a list of species used and cited in clinical research. 4 Table 2. Micro-organisms considered to be probiotics Lactobacillus species Bifidobacterium species Earn free CPD Points Join our CPD community at www.denovomedica.com and start to earn today! L. acidophilus B adolescentis L. casei B animalis L. crispatus B bifidum L. gallinarum (Mainly used by animals) B breve L. gasseri B infantis L. johnsonii B lactis (Recently reclassified as B animalis subsp. lactis) L. paracasei B longum L. plantarum L. reuteri L. rhamnosus 2 I APril 2018
A South African-produced probiotic containing two lactic acid bacteria (L plantarum and Enterococcus mundtii) has been shown to prevent Listeria monocytogenes from colonising the gastrointestinal system of mice. 5 This is a particularly interesting finding in view of the recent listeriosis outbreak and deaths in South Africa. Essential probiotic properties Probiotics need to be able to withstand the harsh gastric environment to reach the intestine and adhere to the mucosal and epithelial surfaces. In vitro tests are used to determine the following desirable properties: i) Acid and bile tolerance; essential for oral administration ii) Adhesion to mucosal and epithelial surfaces to compete with and exclude pathogenic bacteria from the receptor iii) Production of antimicrobial activity against pathogenic bacteria (so that the probiotic can compete even more successfully with pathogenic bacteria) iv) Bile salt hydrolase activity Mechanisms of action Probiotics have various mechanisms of action. These include the production of bacteriocins (antibacterial peptides) and short-chain fatty acids, lowering of gut ph, stimulation of mucosal barrier integrity and immunomodulation. There v) Resistance to certain antibiotics, so that the probiotic is able to restore the microbial balance and prevent antibiotic side-effects vi) Quantity of viable micro-organisms, although not precisely defined, should reach a minimum total of 10 8-10 9 colony-forming units (CFUs). Viability should also be maintained under normal storage conditions. Vaginal probiotics are being developed and trialled to reduce bacterial vaginosis, 6 a condition characterised microbiologically by replacement of the lactobacilli predominant in the vaginal microbiota. is considerable evidence that probiotics influence the acquired and innate immune response by inducing phagocytosis and IgA secretion, modifying helper T-cell response and the release of cytokines in a strain-specific manner. 7 Link between gastrointestinal flora and immune function Probiotics maintain the balance of gastrointestinal microbiota and help to prevent invasion of the epithelium by pathogenic bacteria. The body s immune system is associated with the intestinal epithelial barrier and its mucosal lining. Disruption of the healthy, indigenous microbiota by pathogens leads to a dysfunctional innate immune system and increases the risk of developing disease, including IBS (Figure 1). Safety of probiotic use Probiotics are generally considered to be safe but caution is advised in immunologically vulnerable populations. 2 Available evidence from randomised clinical trials (RCTs) does not indicate an increased risk, but very rare adverse events (bacteraemia/fungaemia/positive blood cultures, five cases in 1557 participants) have been identified in patients with cancer. 8 Specific conditions that benefit from probiotic use While a RCT among free-living older adults was negative for benefit from three months use of probioitics, 9 other RCTs have provided a clearer idea of which patients/people in particular circumstances will benefit from probiotic supplements. APril 2018 I 3
Healthy status Stress/disease Normal gut physiology Abnormal gut function Physiological levels of inflammatory cells/ mediators Normal gut microbiota Increased levels of inflammatory cells/ mediators Intestinal dysbiosis Figure 1. Normal gut flora and immune function Earn free CPD Points Join our CPD community at www.denovomedica.com and start to earn today! Pregnant and lactating women A RCT of high-dose probiotic supplementation of women during late pregnancy and lactation has shown that breast-milk cytokines and secretory IgA production in newborns are beneficially Antibiotic-associated diarrhoea A Cochrane analysis of available clinical trials suggests a positive outcome with regard to the reduction of antibiotic-associated diarrhoea in children with a number needed to treat (NNT) of 10. 11 Among the various probiotics evaluated, L rhamnosus or Saccharomyces boulardii at 5-40 billion CFUs/day may be appropriate given the modest NNT and the likelihood that adverse events are very rare. Although no serious adverse events from probiotic usage have been observed among otherwise healthy children, adverse events have been observed in severely debilitated or immune-compromised modified by therapy. 10 This improves the overall gastrointestinal function in infants of treated mothers with a reduction of colic symptoms. children with underlying risk factors, including central venous catheter use and disorders associated with bacterial/fungal translocation. Until further research has been conducted, probiotic use should be avoided in paediatric populations at risk for adverse events. In healthy adults, a randomised, double-blind placebo-controlled trial of two lactobacilli (L helveticus (R0052) and L rhamnosus R0011), taken for one week with the antibiotic and one week after completion, showed that supplementation significantly reduced the duration of diarrhoea-like symptoms. 12 4 I APril 2018
IBS According to the most recent guideline from the American College of Gastroenterology on the management of IBS, probiotics improve global symptoms, bloating and flatulence in IBS based on meta-analyses of more than 23 RCTs involving 2500 patients. 13 This guideline acknowledges that recommendations concerning which species, preparations or strains to use are difficult because of insufficient and conflicting data. Patients on aspirin to reduce small bowel injuries A very recent prospective randomised double-blind placebo-controlled trial showed that a lactobacillus (L gasseri OLL2716 (LG)) given daily for six weeks reduced aspirin-induced small bowel injuries and mitigated gastrointestinal symptoms. 14 Patients/people vulnerable to adverse effects of respiratory tract infections (RTIs) In the elderly population, upper RTIs can have severe implications. A RCT of people aged 60-74 years, healthy and not living in retirement homes, showed that a Bacillus subtilis CU1 probiotic decreased the frequency of respiratory infections compared to placebo. 15 Probiotic usage in vulnerable children/ immunocompromised children is not recommended to prevent RTIs; however, Cochrane analysis has shown the value of probiotics in otherwise healthy children in reducing the occurrence of RTI s. 7 Athletes in training Trained athletes benefit from probiotic usage as prolonged intense exercise is associated with the suppression of immune function and an increased risk of infections. A randomised, doubleblind placebo-controlled trial conducted Conclusion Probiotic use can be beneficial, particularly to a subset of patients with gastrointestinal problems and can significantly among Austrian athletes showed that a multi-species probiotic given for 12 weeks reduced exercise-induced drops in tryptophan levels and reduced the incidence of upper RTIs without enhancing athletic performance. 16 improve the immune status during treatment. APril 2018 I 5
References Earn free CPD Points Are you a member of Southern Africa s leading digital Continuing Professional Development website earning FREE CPD points with access to best practice content? Only a few clicks and you can register to start earning today Visit www.denovomedica.com For all Southern African healthcare professionals 1. Walker AR. Diet and bowel diseases past history and future prospects. S Afr Med J 1985; 68(3): 148-152. 2. Wilkins T, Seauicoa J. Probiotics for GIT conditions: Summary of the evidence. Am Fam Physician 2017; 96(3): 170-178. 3. De Beer LT, Pienaar J, Rothmann S. Job burnout, work engagement and self-reported treatment for health conditions in South Africa. Wiley Online Library (wileyonlinelibrary.com). https://doi.org/10.1002/ smi.2576 4. Kechagia M, Basoulis D, Konstantopoulou S, et al. Health benefits of probiotics: A review. ISRN Nutrition 2013: http://dx.doi.org/10.5402/2013/481651 5. Van Zyl WF, Dean SM, Dicks LM. Enterococcus mundtii ST4SA and Lactobacillus plantarum 423 excludes Listeria monocytogenes from the GIT as shown by bioluminescent studies in mice. Microbes 2016; 7(2): 227-235. 6. Racine N, Palma E, Domenici L, et al. Restoring vaginal microbiota: biological control of bacterial vaginosis. A prospective case-control study using Lactobacillus rhamnosus BMX 54 as adjuvant treatment against bacterial vaginosis. Arch Gynecol Obstet 2016; 293(1): 101-107. 7. Fong FL, Shah NP, Kirjavainen P, et al. Mechanism of action of probiotic bacteria on intestinal and systemic immunities and antigen-presenting cells. Int Rev Immunol 2016; 35(3): 179-188. 8. Hampel S, Newberry S, Ruelaz A, et al. Safety of probiotics used to treat and prevent or treat disease. Evid Rep Technol Assess (full Rep) 2011; 200: 1-645. 9. Redman MG, Ward EJ, Phillips RS. The efficacy and safety of probiotics in people with cancer: a systematic review. Ann Oncol 2014; 25(10): 1919-1929. 10. Baldassarre ME, Di Mauro A, Mastromarino P, et al. Administration of a multi-strain probiotic product to women in the perinatal period differentially affects the breast milk cytokine profile and may have beneficial effects on neonatal gastrointestinal functional symptoms. A randomised clinical trial. Nutrients 2016; 8(11): pii: E677. 11. Goldenberg JZ, Lytvyn L, Steurich J, et al. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst Rev 2015; Dec 22(12): CD004827. 12. Evans M, Salewski RP, Christman MC; et al. Effectiveness of Lactobacillus helveticus and Lactobacillus rhamnosus for the management of antibiotic-associated diarrhoea in healthy adults: a randomised, double-blind, placebocontrolled trial. Br J Nutr 2016; 116(1): 94-103. 13. Ford AC, Moayyedi P, Lacy BE, et al. American College of Gastroenterology Monograph on the management of IBS and chronic idiopathic constipation. Am J Gastroenterol 2014; 109: S2-S26. 14. Suzuki T, Masui A, Nakamura J, et al. Yogurt containing Lactobacillus gasseri mitigates aspirin-induced small bowel injuries: A prospective, randomised, double-blind, placebo-controlled trial. Digestion 2017; 95(1): 49-54. 15. Lefevre M, Racedo SM, Ripert G, et al. Probiotic strain bacillus subtilis CU1 stimulates immune system of elderly during common infectious disease period: a randomized, double-blind placebo-controlled study. Immun Ageing 2015; 12: 24. doi: 10.1186/s12979-015-0051-y. 16. Strasser B, Geiger D, Schauer M, et al. Probiotic supplements beneficially affect tryptophan-kynurenine metabolism and reduce the incidence of upper respiratory tract infections in trained athletes: A randomised, double-blinded, placebo-controlled trial. Nutrients 2016; 8(11): 752. doi: 10.3390/nu8110752. Find us at DeNovo Medica @denovomedica Disclaimer The views and opinions expressed in the article are those of the presenters and do not necessarily reflect those of the publisher or its sponsor. In all clinical instances, medical practitioners are referred to the product insert documentation as approved by relevant control authorities. Published by denovo Medica Reg: 2012/216456/07 70 Arlington Street, Everglen, Cape Town, 7550 Tel: (021) 976 0485 I info@denovomedica.com 6 I APril 2018