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GP symposium 2019: Updates on the Use of Probiotics in Clinical Practice
24 Apr 2019
Modulation of gut microbiota with probiotics has been studied in a wide range of clinical settings, in the hope of achieving health benefits in the host. Under the auspices of the Asian GI Faculty, four experts discussed the role of probiotics in clinical practice at the recent IMPACT (Improving Medical Practice through Advancement in Clinical Treatment) GP symposium in Singapore sponsored by DCH Auriga.
Probiotics have been marketed for a wide range of conditions, particularly gut health. In view of this, the South-East Asian Gastro-Neuro Motility Association (SEAGMA) published statements on the use of probiotics for selected gastrointestinal conditions (Table 1).1
Probiotics are heterogenous with a wide variability of microbial species and quantity; they produce varying outcomes in differing clinical situations. The SEAGMA report recognizes that not all probiotics have proven efficacy for irritable bowel syndrome (IBS).2,3 In a randomized controlled trial (RCT), Bifidobacterium (B.) infantis significantly improved abdominal pain, bloating/distension and bowel movement difficulty in IBS patients but Lactobacillus (L.) salivarius did not,4 while other studies with L. casei Shirota5 and Escherichia (E.) coli Nissle 19176 failed to show significant improvement over placebo.
Also, multistrain probiotics may be more effective than single-strain probiotics for IBS; though L. rhamnosus GG (LGG) as a single species was ineffective in adult IBS subjects,7,8 multispecies probiotics containing LGG could have some efficacy.9,10
Importantly, appropriate dosing, as guided by clinical evidence is important to achieve intended clinical effect of a probiotic treatment. Higher doses of probiotics are not necessarily more effective, as shown by a study evaluating three doses of B. infantis in IBS, where the medium dose outperformed the highest and lowest doses.11
The quality and health claims of probiotics classified as health supplements, are undetermined. Microbiological evaluations of probiotic health supplements revealed inconsistencies between the label claims and actual probiotic strain identified, and sizeable loss of microbial load was observed during storage.12,13 Unlike probiotic health supplements, which often lack robust efficacy data, Duolac® Daily Vitality has been shown in an RCT to be significantly more effective than placebo in reducing symptoms in adult IBS patients.9,10 It also has a patented dual-coating pH-dependent release mechanism, which protects the probiotics from gastric acid and bile salt to ensure delivery to the intestine.
In conclusion, it is important to obtain clinical evidence of efficacy for specific strains and dosing of probiotics for specific conditions in the relevant patient population.
The human microbiome influences immunological, endocrine, and neural pathways and plays an important role in infant development. The colonization and maturation of infant gut microbiome depend on genetic and environmental factors such as type of birth, milk-feeding practices and intake of antibiotics.14,15
Dysbiosis, the loss of beneficial bacteria and bacterial diversity which encourages overgrowth of pathogenic bacteria, has been associated with the development of chronic diseases in later life,16 including obesity17 and autism18. Probiotics are used in an attempt to ameliorate dysbiosis by introducing certain beneficial microbes to the patient.
The SEAGMA working team has published statements on probiotic use in common childhood digestive disorders (Table 1). They state that probiotics are beneficial in treating acute gastroenteritis (AGE) in children and decrease the incidence of antibiotic-associated diarrhoea (AAD), but are neither useful in constipation nor managing childhood obesity.1 Meta-analyses show that Saccharomyces (S.) boulardii, L. reuteri DSM 17938, and LGG, reduce the duration of diarrhoea in childhood AGE by 1–2 days,19–21 while the use of S. boulardii and LGG decrease the incidence of AAD in children versus placebo.22
In preclinical studies, B. longum and B. bifidum shielded the gut from gluten and potentially counteracted the inflammatory effects of altered microbiota present in coeliac disease.23 In addition, the introduction of gut microbiota to germ-free mice has been shown to induce insulin-like growth factor (IGF-1) and promote bone formation and growth.24
In summary, manipulating the microbiome or its metabolites may afford opportunities to optimize gut health, bone health, and growth in children.
Atopic dermatitis (AD) is a chronically relapsing skin condition, which commonly begins in early childhood, with approximately half persisting into adulthood. It has a reported prevalence of 15–30 percent in childhood and 2–10 percent in adults.25–27
The pathogenesis of AD is multifactorial, involving multiple genes, altered immune responses, skin barrier dysfunction and environmental risk factors.28 The gut microbiome may contribute to the development, persistence, and severity of AD via immunologic, metabolic, and neuroendocrine pathways.28 Emerging data support the presence of a gut-skin axis mediated by neuroendocrine and immunomodulatory effects produced by the gut microbiome, that can affect skin barrier dysfunction and immune system dysregulation, which further drives AD.28 Compared with controls, patients with AD have been reported to have increased C. difficile, E. coli, Staphylococcus aureus and decreased bifidobacteria and bacteroides28 in their gut and stools. Perturbations of the infant gut microbiota through various factors, such as feeding and diet, can influence the gut-skin immune response, affecting the risk of AD.29
Strategies for the primary prevention of AD include barrier protection through early emollient use30,31 and immune modulation through the use of probiotics.32–34 Recent meta-analyses demonstrate that maternal probiotic supplementation during gestation may have a preventative effect on AD onset.34 The World Allergy Organization recommends probiotics in pregnant and breastfeeding women as well as infants, with a high risk of atopic predisposition.32
The use of probiotics as an adjunctive, secondary treatment of AD has yielded mixed results. Some multistrain probiotics may be effective in improving symptoms of AD in children36,37 In particular, a recently published observational prospective study showed that supplementation of a symbiotic product (Duolac® Derma, containing B. lactis, L. casei, L. rhamnosus, and L. plantarum) for 8 weeks decreased the mean SCORAD index, VAS score for pruritis and VAS score for sleep compared with baseline in children with AD.37 Further research is required to determine the optimal strains, dose, duration and indications for the use of probiotics in the treatment of AD.
In recent decades, the role of gut microbiota has been extensively researched in the triangle of nutrition, health, and diseases. Numerous studies explored the composition and functionality of the infant gut microbiome and found associations with disease states in later life. This concept has prompted the development of strategies to shape the infant microbiota composition, such as use of probiotics and other food products.
An example of this is Duolac® Duo D-drops, which contains a patented mixture of four kinds of bifidobacteria (B. longum, B. infantis, B. breve, and B. bifidum) with vitamin D for convenient administration. These bifidobacterium species have been isolated from infant faeces and have undergone whole genome sequencing (WGS).38 WGS showed that these strains encode proteins for several metabolic pathways, including urea metabolism, which helps infants metabolize nitrogen content in breast milk and help promote development and growth; the biosynthesis of vitamin B2, B3, and B9, which are important for promoting healthy metabolism; and the production of bacteriocin, which inhibits the growth of harmful bacteria and maintains balance of intestinal microbiota.38
Notably, the four bifidobacteria strains in Duolac® Duo D-drops are major bacteria in breast milk and are frequently detected in the breastfed infant gut.39 Vitamin D is added because vitamin D deficiency has been associated with dysbiosis and studies suggest that probiotics elevate vitamin D absorption.40
A placebo-controlled intervention study in infants showed that supplementation with B. longum, B. infantis, B. breve, and B. bifidum modulates the infant microbiome at very early stages in life with no detectable long-term consequences for gut microbiota assembly or function.39 No adverse effects were reported, establishing safety of this probiotic supplement.39
Probiotics have been marketed for a wide range of conditions, particularly gut health. In view of this, the South-East Asian Gastro-Neuro Motility Association (SEAGMA) published statements on the use of probiotics for selected gastrointestinal conditions (Table 1).1
Probiotics are heterogenous with a wide variability of microbial species and quantity; they produce varying outcomes in differing clinical situations. The SEAGMA report recognizes that not all probiotics have proven efficacy for irritable bowel syndrome (IBS).2,3 In a randomized controlled trial (RCT), Bifidobacterium (B.) infantis significantly improved abdominal pain, bloating/distension and bowel movement difficulty in IBS patients but Lactobacillus (L.) salivarius did not,4 while other studies with L. casei Shirota5 and Escherichia (E.) coli Nissle 19176 failed to show significant improvement over placebo.
Also, multistrain probiotics may be more effective than single-strain probiotics for IBS; though L. rhamnosus GG (LGG) as a single species was ineffective in adult IBS subjects,7,8 multispecies probiotics containing LGG could have some efficacy.9,10
Importantly, appropriate dosing, as guided by clinical evidence is important to achieve intended clinical effect of a probiotic treatment. Higher doses of probiotics are not necessarily more effective, as shown by a study evaluating three doses of B. infantis in IBS, where the medium dose outperformed the highest and lowest doses.11
The quality and health claims of probiotics classified as health supplements, are undetermined. Microbiological evaluations of probiotic health supplements revealed inconsistencies between the label claims and actual probiotic strain identified, and sizeable loss of microbial load was observed during storage.12,13 Unlike probiotic health supplements, which often lack robust efficacy data, Duolac® Daily Vitality has been shown in an RCT to be significantly more effective than placebo in reducing symptoms in adult IBS patients.9,10 It also has a patented dual-coating pH-dependent release mechanism, which protects the probiotics from gastric acid and bile salt to ensure delivery to the intestine.
In conclusion, it is important to obtain clinical evidence of efficacy for specific strains and dosing of probiotics for specific conditions in the relevant patient population.
The human microbiome influences immunological, endocrine, and neural pathways and plays an important role in infant development. The colonization and maturation of infant gut microbiome depend on genetic and environmental factors such as type of birth, milk-feeding practices and intake of antibiotics.14,15
Dysbiosis, the loss of beneficial bacteria and bacterial diversity which encourages overgrowth of pathogenic bacteria, has been associated with the development of chronic diseases in later life,16 including obesity17 and autism18. Probiotics are used in an attempt to ameliorate dysbiosis by introducing certain beneficial microbes to the patient.
The SEAGMA working team has published statements on probiotic use in common childhood digestive disorders (Table 1). They state that probiotics are beneficial in treating acute gastroenteritis (AGE) in children and decrease the incidence of antibiotic-associated diarrhoea (AAD), but are neither useful in constipation nor managing childhood obesity.1 Meta-analyses show that Saccharomyces (S.) boulardii, L. reuteri DSM 17938, and LGG, reduce the duration of diarrhoea in childhood AGE by 1–2 days,19–21 while the use of S. boulardii and LGG decrease the incidence of AAD in children versus placebo.22
In preclinical studies, B. longum and B. bifidum shielded the gut from gluten and potentially counteracted the inflammatory effects of altered microbiota present in coeliac disease.23 In addition, the introduction of gut microbiota to germ-free mice has been shown to induce insulin-like growth factor (IGF-1) and promote bone formation and growth.24
In summary, manipulating the microbiome or its metabolites may afford opportunities to optimize gut health, bone health, and growth in children.
Atopic dermatitis (AD) is a chronically relapsing skin condition, which commonly begins in early childhood, with approximately half persisting into adulthood. It has a reported prevalence of 15–30 percent in childhood and 2–10 percent in adults.25–27
The pathogenesis of AD is multifactorial, involving multiple genes, altered immune responses, skin barrier dysfunction and environmental risk factors.28 The gut microbiome may contribute to the development, persistence, and severity of AD via immunologic, metabolic, and neuroendocrine pathways.28 Emerging data support the presence of a gut-skin axis mediated by neuroendocrine and immunomodulatory effects produced by the gut microbiome, that can affect skin barrier dysfunction and immune system dysregulation, which further drives AD.28 Compared with controls, patients with AD have been reported to have increased C. difficile, E. coli, Staphylococcus aureus and decreased bifidobacteria and bacteroides28 in their gut and stools. Perturbations of the infant gut microbiota through various factors, such as feeding and diet, can influence the gut-skin immune response, affecting the risk of AD.29
Strategies for the primary prevention of AD include barrier protection through early emollient use30,31 and immune modulation through the use of probiotics.32–34 Recent meta-analyses demonstrate that maternal probiotic supplementation during gestation may have a preventative effect on AD onset.34 The World Allergy Organization recommends probiotics in pregnant and breastfeeding women as well as infants, with a high risk of atopic predisposition.32
The use of probiotics as an adjunctive, secondary treatment of AD has yielded mixed results. Some multistrain probiotics may be effective in improving symptoms of AD in children36,37 In particular, a recently published observational prospective study showed that supplementation of a symbiotic product (Duolac® Derma, containing B. lactis, L. casei, L. rhamnosus, and L. plantarum) for 8 weeks decreased the mean SCORAD index, VAS score for pruritis and VAS score for sleep compared with baseline in children with AD.37 Further research is required to determine the optimal strains, dose, duration and indications for the use of probiotics in the treatment of AD.
In recent decades, the role of gut microbiota has been extensively researched in the triangle of nutrition, health, and diseases. Numerous studies explored the composition and functionality of the infant gut microbiome and found associations with disease states in later life. This concept has prompted the development of strategies to shape the infant microbiota composition, such as use of probiotics and other food products.
An example of this is Duolac® Duo D-drops, which contains a patented mixture of four kinds of bifidobacteria (B. longum, B. infantis, B. breve, and B. bifidum) with vitamin D for convenient administration. These bifidobacterium species have been isolated from infant faeces and have undergone whole genome sequencing (WGS).38 WGS showed that these strains encode proteins for several metabolic pathways, including urea metabolism, which helps infants metabolize nitrogen content in breast milk and help promote development and growth; the biosynthesis of vitamin B2, B3, and B9, which are important for promoting healthy metabolism; and the production of bacteriocin, which inhibits the growth of harmful bacteria and maintains balance of intestinal microbiota.38
Notably, the four bifidobacteria strains in Duolac® Duo D-drops are major bacteria in breast milk and are frequently detected in the breastfed infant gut.39 Vitamin D is added because vitamin D deficiency has been associated with dysbiosis and studies suggest that probiotics elevate vitamin D absorption.40
A placebo-controlled intervention study in infants showed that supplementation with B. longum, B. infantis, B. breve, and B. bifidum modulates the infant microbiome at very early stages in life with no detectable long-term consequences for gut microbiota assembly or function.39 No adverse effects were reported, establishing safety of this probiotic supplement.39