Probiotics for the Treatment of Irritable Bowel Syndrome
Background Irritable bowel syndrome (IBS) is a poorly understood, yet highly prevalent functional gastrointestinal disorder (FGID). The withdrawal, due to adverse events, of a number of pharmacological agents that were approved for the treatment of IBS has left a therapeutic vacuum for patients suffering from the disorder.
Aim To review, summarise and critically evaluate current knowledge of lactic acid bacteria (LAB) used to treat IBS.
Methods We assessed a comprehensive range of relevant literature from Pubmed, Medline and online sources based on our definition of LAB which included both typical and atypical species, covering Lactobacilli,Bifidobacteria,Enterococci,Streptococci and Bacilli.
Results Of the 42 trials evaluated examining the efficacy of LAB in IBS, 34 reported beneficial effects in at least one of the endpoints or symptoms examined, albeit with tremendous variation in both the magnitude of effect and the choice of outcome under consideration. However, numerous concerns have been expressed over deficits of trial design and execution relating to strain selection, optimum dosage, mode of action, safety and long-term tolerability in a disorder that can persist throughout the lifetime of affected individuals.
Conclusions Progress in the field will require an improved understanding of how the microbiota impacts on health and disease, adequately powered long-term multicentre trials and the embracing of bench to bedside approaches. Recent incremental advances suggest these areas are being addressed and that the future holds much promise for the use of lactic acid bacteria in the treatment of irritable bowel syndrome
Irritable bowel syndrome (IBS) is a very common functional gastrointestinal disorder (FGID) which impacts the individual as well as society. At the individual level, patients experience recurrent abdominal pain or discomfort and an alteration in bowel habit along with a range of other features including bloating, distension, flatulence, borborygmi and disturbances in defecatory function. These symptoms range from mild to severe and although the prognosis for IBS is benign, the overall impact can engender serious disruptions in an individual's well being and quality of life. Moreover, for many it is a life-long affliction, marked by unpredictable flares of activity and periods of remission. At the macroeconomic level, given an estimated prevalence in industrialised countries of 10–15% and its recognised association with work absenteeism and presenteeism, IBS, undoubtedly, exerts a significant drain on a nation's economy.
Within the clinical realm, where it is the disorder most frequently encountered by gastroenterologists, the impact is no less disconcerting. Despite the regularity with which the disorder is encountered and the considerable resources deployed towards its treatment, it is still poorly understood and the diagnosis of IBS is commonly based solely on symptom-based criteria such as the 'Rome Criteria' following the exclusion of organic diseases of the gastrointestinal tract (GIT), the latter an expensive process in itself. Traditionally, pathophysiological insights into the cardinal symptoms of the disorder have centred on the primacy of visceral hypersensitivity in the development of pain or discomfort, and on the impact of gut dysmotility in the development of the underlying disturbance in bowel habit. The more holistic concept of a dysregulated brain-gut axis has integrated these separate theories into a more complex view of IBS aetiology. This theory drew on the principle that bidirectional signalling between the gastrointestinal tract and the brain (regulated at neural, hormonal and immunological levels) is vital for maintaining homeostasis; perturbation of these systems leads to disease states. Despite these advances, IBS is still largely characterised by the lack of a reliable biological marker and inadequate treatment options.
The dearth of successful pharmacological interventions has shifted the gaze of the research community away from the largely failed strategy of drug development based on visceral hypersensitivity and gut dysmotility towards other facets of the brain-gut axis construct. This is an especially pressing goal given the withdrawal of agents that held promise in the treatment of IBS like alosetron, cilansetron and tegaserod, due to adverse events. Thus, in addition to visceral hypersensitivity and dysmotility, altered central nervous system perception of visceral events and psychopathology as well as infection and inflammation are now routinely considered as important pathophysiological factors. The importance of the microbiota within the brain-gut axis construct has also seen the emergence of the bacterial flora as a therapeutic target with the use of antibiotics and probiotics being the primary means of intervention.
In this review, we focus on the rationale behind this approach and provide an overview of the clinical trials that have used lactic acid bacteria (LAB), the most commonly used bacteria in probiotic preparations, to modulate the gut microbiome and in doing so evaluate their effects on the cardinal symptoms of IBS (abdominal pain/discomfort, bloating/distension, alterations in defecatory function), other benefits (flatulence, borborygmi), as well as more global indices. We also explore the mechanistic insights that have been gained from both clinical and preclinical datasets and examine the gaps in knowledge that still exist surrounding this treatment strategy. Finally, the challenges facing researchers and clinicians in this area are evaluated and the obstacles that need to be cleared to allow further progress in this field outlined. For the purposes of this review, our definition of LAB includes both typical and atypical species, covering Lactobacilli, Bifidobacteria, Enterococci and Streptococci and Bacilli. Although we acknowledge that not all the strains discussed are 'true' lactic acid bacteria in the strictest sense, it is important to point out that the term itself owes more to a functional classification than to a taxonomical description.
Abstract and Introduction
Abstract
Background Irritable bowel syndrome (IBS) is a poorly understood, yet highly prevalent functional gastrointestinal disorder (FGID). The withdrawal, due to adverse events, of a number of pharmacological agents that were approved for the treatment of IBS has left a therapeutic vacuum for patients suffering from the disorder.
Aim To review, summarise and critically evaluate current knowledge of lactic acid bacteria (LAB) used to treat IBS.
Methods We assessed a comprehensive range of relevant literature from Pubmed, Medline and online sources based on our definition of LAB which included both typical and atypical species, covering Lactobacilli,Bifidobacteria,Enterococci,Streptococci and Bacilli.
Results Of the 42 trials evaluated examining the efficacy of LAB in IBS, 34 reported beneficial effects in at least one of the endpoints or symptoms examined, albeit with tremendous variation in both the magnitude of effect and the choice of outcome under consideration. However, numerous concerns have been expressed over deficits of trial design and execution relating to strain selection, optimum dosage, mode of action, safety and long-term tolerability in a disorder that can persist throughout the lifetime of affected individuals.
Conclusions Progress in the field will require an improved understanding of how the microbiota impacts on health and disease, adequately powered long-term multicentre trials and the embracing of bench to bedside approaches. Recent incremental advances suggest these areas are being addressed and that the future holds much promise for the use of lactic acid bacteria in the treatment of irritable bowel syndrome
Introduction
Irritable bowel syndrome (IBS) is a very common functional gastrointestinal disorder (FGID) which impacts the individual as well as society. At the individual level, patients experience recurrent abdominal pain or discomfort and an alteration in bowel habit along with a range of other features including bloating, distension, flatulence, borborygmi and disturbances in defecatory function. These symptoms range from mild to severe and although the prognosis for IBS is benign, the overall impact can engender serious disruptions in an individual's well being and quality of life. Moreover, for many it is a life-long affliction, marked by unpredictable flares of activity and periods of remission. At the macroeconomic level, given an estimated prevalence in industrialised countries of 10–15% and its recognised association with work absenteeism and presenteeism, IBS, undoubtedly, exerts a significant drain on a nation's economy.
Within the clinical realm, where it is the disorder most frequently encountered by gastroenterologists, the impact is no less disconcerting. Despite the regularity with which the disorder is encountered and the considerable resources deployed towards its treatment, it is still poorly understood and the diagnosis of IBS is commonly based solely on symptom-based criteria such as the 'Rome Criteria' following the exclusion of organic diseases of the gastrointestinal tract (GIT), the latter an expensive process in itself. Traditionally, pathophysiological insights into the cardinal symptoms of the disorder have centred on the primacy of visceral hypersensitivity in the development of pain or discomfort, and on the impact of gut dysmotility in the development of the underlying disturbance in bowel habit. The more holistic concept of a dysregulated brain-gut axis has integrated these separate theories into a more complex view of IBS aetiology. This theory drew on the principle that bidirectional signalling between the gastrointestinal tract and the brain (regulated at neural, hormonal and immunological levels) is vital for maintaining homeostasis; perturbation of these systems leads to disease states. Despite these advances, IBS is still largely characterised by the lack of a reliable biological marker and inadequate treatment options.
The dearth of successful pharmacological interventions has shifted the gaze of the research community away from the largely failed strategy of drug development based on visceral hypersensitivity and gut dysmotility towards other facets of the brain-gut axis construct. This is an especially pressing goal given the withdrawal of agents that held promise in the treatment of IBS like alosetron, cilansetron and tegaserod, due to adverse events. Thus, in addition to visceral hypersensitivity and dysmotility, altered central nervous system perception of visceral events and psychopathology as well as infection and inflammation are now routinely considered as important pathophysiological factors. The importance of the microbiota within the brain-gut axis construct has also seen the emergence of the bacterial flora as a therapeutic target with the use of antibiotics and probiotics being the primary means of intervention.
In this review, we focus on the rationale behind this approach and provide an overview of the clinical trials that have used lactic acid bacteria (LAB), the most commonly used bacteria in probiotic preparations, to modulate the gut microbiome and in doing so evaluate their effects on the cardinal symptoms of IBS (abdominal pain/discomfort, bloating/distension, alterations in defecatory function), other benefits (flatulence, borborygmi), as well as more global indices. We also explore the mechanistic insights that have been gained from both clinical and preclinical datasets and examine the gaps in knowledge that still exist surrounding this treatment strategy. Finally, the challenges facing researchers and clinicians in this area are evaluated and the obstacles that need to be cleared to allow further progress in this field outlined. For the purposes of this review, our definition of LAB includes both typical and atypical species, covering Lactobacilli, Bifidobacteria, Enterococci and Streptococci and Bacilli. Although we acknowledge that not all the strains discussed are 'true' lactic acid bacteria in the strictest sense, it is important to point out that the term itself owes more to a functional classification than to a taxonomical description.
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