Current level of consensus on probiotic science--report of an expert meeting--London, 23 November 2009

The present paper summarizes the consensus views of a group of 9 European clinicians and scientists on the current state of scientific knowledge on probiotics, covering those areas where there is substantial evidence for beneficial effects and those where the evidence base is poor or inconsistent. There was general agreement that probiotic effects were species and often strain specific. The experts agreed that some probiotics were effective in reducing the incidence and duration of rotavirus diarrhoea in infants, antibiotic-associated diarrhoea in adults and, for certain probiotics, Clostridium difficile infections. Some probiotics are associated with symptomatic improvements in irritable bowel syndrome and alleviation of digestive discomfort. Probiotics can reduce the frequency and severity of necrotizing enterocolitis in premature infants and have been shown to regulate intestinal immunity. Several other clinical effects of probiotics, including their role in inflammatory bowel disease, atopic dermatitis, respiratory or genito-urinary infections or H.pylori adjuvant treatment were thought promising but inconsistent.     

Probiotics and gastrointestinal diseases

There is increasing evidence indicating health benefits by consumption of foods containing microorganisms, i.e. probiotics. A number of clinical trials have been performed to evaluate the effects in the prevention and treatment of gastrointestinal diseases caused by pathogenic microorganisms or by disturbances in the normal microflora. Gastrointestinal infections caused by Helicobacter pylori, traveller's diarrhoea, rotavirus diarrhoea, antibiotic-associated diarrhoea (AAD) and Clostridium difficile-induced diarrhoea are conditions that have been studied. There are also studies performed on the preventive effect of probiotics on radiation-induced diarrhoea and diarrhoea in tube-fed patients. Inflammatory bowel disease and irritable bowel syndrome, two idiopathic conditions where alterations in the normal microflora have been implicated as responsible for initiation, are two further areas where the use of probiotics has been regarded as promising. The results from clinical studies have not been conclusive in that the effects of probiotics have been strain-dependent and different study designs have been used. Treatment of acute diarrhoea in children and prevention of AAD are the two most justified areas for the application of probiotics.     

Probiotics in infective diarrhoea and inflammatory bowel diseases

Bacteria are present throughout the gastrointestinal tract, but their pattern and concentration vary greatly. Probiotics are living organisms that supply beneficial health effects to the host. So far the beneficial effects of probiotics have been shown, almost exclusively, under poorly defined experimental conditions. There are little convincing data from well-designed, double-blind controlled trials supporting health-promoting effects. The use of probiotics to treat gastrointestinal infections has produced contrasting results. Apart from information on rotavirus infection in children, there is no convincing evidence from controlled studies on the efficacy of probiotics in the prevention or treatment of infective diarrhoea. However, experimental and clinical studies suggest that there are potential therapeutic roles for probiotics in the treatment of inflammatory bowel diseases. This review focuses on the available data concerning the mechanisms of action of probiotics, and on the results from clinical studies using probiotics to treat infective diarrhoea and inflammatory bowel disease.     

Probiotics in gastroenterology: indications and future perspectives

Nowadays. there is a growing interest in probiotics as a safe way of changing the intestinal bacterial flora. Probiotics may have potential in several gastroenterological conditions, especially when the intestinal flora has been disturbed. Most scientific evidence is available for diarrhoea patients treated with Lactobacillus GG, Lactobacillus reuteri or Saccharomyces boulardii. Meta-analyses have shown an overall reduction in the risk of antibiotic-associated diarrhoea during treatment with probiotics, and benefits have also been demonstrated for patients with rota-virus-associated diarrhoea. Patients with inflammatory bowel disease, an inflammatory disorder characterized by a change in the intestinal flora, are another important target group for which probiotics may be beneficial. It has been claimed that in ulcerative colitis and Crohn disease patients, lactobacilli, S. boulardii and Escherichia coli reduce relapses. but most studies were not placebo-controlled. A reduction in relapses has also been demonstrated in pouchitis patients treated with a multispecies probiotic. Irritable bowel syndrome might be another clinical indication for probiotic therapy, but results of clinical trials performed in these patients are inconsistent. Additionally, probiotics may improve lactose absorption. Helicobacter pylori eradication and constipation. Finally, in animal models of colorectal cancer, treatment with probiotics reduces the prevalence of this disease, and in humans the amount of genotoxic substances in faeces has been reduced. In conclusion, the results of studies on the effects of probiotics in gastrointestinal conditions are encouraging. but well-designed placebo-controlled studies are warranted before recommendations for therapeutic or preventive use can be given. Many issues still have to be resolved, including optimal dose and duration of treatment, selection of and differences between the several available probiotic strains, and, importantly, their mechanisms of actions have to be elucidated.     

Enteric viral infections as a cause of diarrhoea in the acquired immunodeficiency syndrome

Background and aims The role of non-cytomegalovirus (CMV) enteric viral infection in causing diarrhoea in patients with human immunodeficiency virus (HIV) is poorly understood. We aimed to investigate the prevalence of these infections in acute and chronic diarrhoea. Methods Stool specimens from 377 HIV-infected patients presenting with diarrhoea were studied prospectively for evidence of non-CMV enteric viral infection. Patients with diarrhoea underwent investigation for gastrointestinal pathogens, including electron microscopic examination of stool for enteric viruses. We collected data on patients in whom enteric virus was identified and examined the association of enteric virus infection with diarrhoeal symptomatology. Results Eighty-nine (10.3%) stool specimens from 60 (15.9%) HIV⁺ individuals were positive for coronavirus (n = 13, 22%), rotavirus (n = 11, 18%), adenovirus (n = 30, 50%) and small round structured viruses (n = 5, 8%) or dual infection (n = 2, 3%). Thirty-four of 52 (65%) patients available for analysis had acute diarrhoea, and 18/52 (35%) had chronic diarrhoea. Twenty-three of 52 (44%) patients had a concurrent gut pathogen. After exclusion of concurrent pathogens enteric viral infections were found to be significantly associated with acute as opposed to chronic diarrhoea (P = 0.004). The presence of adenovirus colitis was significantly more likely to be associated with chronic diarrhoea (15/21 cases) than adenovirus isolated from stool alone (9/23 cases) (P = 0.03). There was a trend towards an association between adenovirus colitis and colonic cytomegalovirus infection (P = 0.06). Conclusion Enteric viral infection is strongly associated with acute diarrhoea in patients with HIV. Light microscopic examination of large bowel biopsies can identify adenovirus colitis which is significantly associated with chronic diarrhoea, and in addition may facilitate gastrointestinal co-infection with CMV.     

Probiotics and Prebiotics in Infants and Children

Probiotics and prebiotics have a major influence on gastrointestinal flora composition. This review analyses the relationship between this change in flora composition and health benefits in children. Literature databases were searched for relevant articles. Despite exhaustive research on the subject in different indications, such as prevention and treatment of acute gastroenteritis, antibiotic associated diarrhea (AAD), traveler's diarrhea, inflammatory bowel disease, irritable bowel syndrome, Helicobacter pylori, necrotizing enterocolitis, constipation, allergy and atopic dermatitis, colic and extraintestinal infections, reports of clear benefits for the use of prebiotics and probiotics in pediatric disorders remain scarce. The best evidence has been provided for the use of probiotics in acute gastroenteritis and in prevention of AAD. However, AAD in children is in general mild, and only seldom necessitates additional interventions. Overall, the duration of acute infectious diarrhea is reduced by approximately 24 hours. Evidence for clinically relevant benefit in all other indications (inflammatory bowel disease, irritable bowel syndrome, constipation, allergy) is weak to nonexistent. Selected probiotic strains given during late pregnancy and early infancy decrease atopic dermatitis. Adverse effects have very seldom been reported. Since the risk seems minimal to nonexistent, prebiotics and probiotics may be helpful in the prevention and treatment of some disorders in children, although the evidence for benefit is limited. The best evidence has been accumulated for some lactobacilli strains and for Saccharomyces boulardii in the reduction of the duration of acute diarrhea due to gastroenteritis and prevention of AAD.     

Probiotics to enhance anti-infective defences in the gastrointestinal tract

Several clinical studies have demonstrated the therapeutic and/or prophylactic efficacy of specific probiotics against acute viral gastroenteritis and antibiotic-associated diarrhoea (including Clostridium difficile infection). Emerging evidence also suggests beneficial effects against Helicobacter pylori infection. The evidence of efficacy against traveller's diarrhoea remains, however, inconclusive. The precise mechanisms by which probiotics potentiate host gastrointestinal defences and mediate protection are not fully known. There is evidence to suggest, however, that probiotics might contribute to host defence by reinforcing non-immunological defences and stimulating both specific and non-specific host immune responses. Little is known about the relative importance of the probiotic-stimulated mechanisms in host protection. This review summarises the evidence for the anti-infective effects of probiotics and discusses the effect of orally delivered probiotics on non-immunological and immunological defence mechanisms in the host, especially in the gastrointestinal tract.     

Gut dysbiosis and irritable bowel syndrome: The potential role of probiotics

Objective

To discuss the role of gut dysbiosis in the development of irritable bowel syndrome (IBS) and the impact of probiotics as a potential therapeutic measure.

Efficacy of probiotics in prevention of acute diarrhoea: a meta-analysis of masked, randomised, placebo-controlled trials

To evaluate the evidence for the use of probiotics in the prevention of acute diarrhoea, we did a meta-analysis of the available data from 34 masked, randomised, placebo-controlled trials. Only one trial was community based and carried out in a developing country. Most of the remaining 33 studies were carried out in a developed country in a health-care setting. Evaluating the evidence by types of acute diarrhoea suggests that probiotics significantly reduced antibiotic-associated diarrhoea by 52% (95% CI 35-65%), reduced the risk of travellers' diarrhoea by 8% (-6 to 21%), and that of acute diarrhoea of diverse causes by 34% (8-53%). Probiotics reduced the associated risk of acute diarrhoea among children by 57% (35-71%), and by 26% (7-49%) among adults. The protective effect did not vary significantly among the probiotic strains Saccharomyces boulardii, Lactobacillus rhamnosus GG, Lactobacillus acidophilus, Lactobacillus bulgaricus, and other strains used alone or in combinations of two or more strains. Although there is some suggestion that probiotics may be efficacious in preventing acute diarrhoea, there is a lack of data from community-based trials and from developing countries evaluating the effect on acute diarrhoea unrelated to antibiotic usage. The effect on acute diarrhoea is dependent on the age of the host and genera of strain used.     

Enhancing immunity in viral infections,with special emphasis on COVID-19: A review

Background and aimsBalanced nutrition which can help in maintaining immunity is essential for prevention and management of viral infections. While data regarding nutrition in coronavirus infection (COVID-19) are not available, in this review, we aimed to evaluate evidence from previous clinical trials that studied nutrition-based interventions for viral diseases (with special emphasis on respiratory infections), and summarise our observations.MethodsA systematic search strategy was employed using keywords to search the literature in 3 key medical databases: PubMed®, Web of Science® and SciVerse Scopus®. Studies were considered eligible if they were controlled trials in humans, measuring immunological parameters, on viral and respiratory infections. Clinical trials on vitamins, minerals, nutraceuticals and probiotics were included.ResultsA total of 640 records were identified initially and 22 studies were included from other sources. After excluding duplicates and articles that did not meet the inclusion criteria, 43 studies were obtained (vitamins: 13; minerals: 8; nutraceuticals: 18 and probiotics: 4). Among vitamins, A and D showed a potential benefit, especially in deficient populations. Among trace elements, selenium and zinc have also shown favourable immune-modulatory effects in viral respiratory infections. Several nutraceuticals and probiotics may also have some role in enhancing immune functions. Micronutrients may be beneficial in nutritionally depleted elderly population.ConclusionsWe summaries possible benefits of some vitamins, trace elements, nutraceuticals and probiotics in viral infections. Nutrition principles based on these data could be useful in possible prevention and management of COVID-19     

Intestinal microbiota,probiotics and prebiotics in inflammatory bowel disease

It has been presumed that aberrant immune response to intestinal microorganisms in genetically predisposed individuals may play a major role in the pathogenesis of the inflammatory bowel disease, and there is a good deal of evidence supporting this hypothesis. Commensal enteric bacteria probably play a central role in pathogenesis, providing continuous antigenic stimulation that causes chronic intestinal injury. A strong biologic rationale supports the use of probiotics and prebiotics for inflammatory bowel disease therapy. Many probiotic strains exhibit anti-inflammatory properties through their effects on different immune cells, pro-inflammatory cytokine secretion depression, and the induction of anti-inflammatory cytokines. There is very strong evidence supporting the use of multispecies probiotic VSL#3 for the prevention or recurrence of postoperative pouchitis in patients. For treatment of active ulcerative colitis, as well as for maintenance therapy, the clinical evidence of efficacy is strongest for VSL#3 and Escherichia coli Nissle 1917. Moreover, some prebiotics, such as germinated barley foodstuff, Psyllium or oligofructose-enriched inulin, might provide some benefit in patients with active ulcerative colitis or ulcerative colitis in remission. The results of clinical trials in the treatment of active Crohn’s disease or the maintenance of its remission with probiotics and prebiotics are disappointing and do not support their use in this disease. The only exception is weak evidence of advantageous use of Saccharomyces boulardii concomitantly with medical therapy in maintenance treatment.     

Effects of Exopolysaccharide-Producing Probiotic Strains on Experimental Colitis in Rats

Purpose Inflammatory bowel disease is suggested to result from a dysregulated immune response toward intestinal microflora, which may be restored by probiotic therapy based on the concept of healthy microflora. Ideal probiotic bacteria may be beneficial in inflammatory bowel disease; however, the mechanism of action and the clinical efficacy of probiotic usage are still unclear. In the present study, the effect of exopolysaccharide producing probiotics was evaluated on an experimental colitis model in rats. Methods Colitis was induced by intracolonic administration of acetic acid. Then, rats were treated daily with two probiotic strains, Lactobacillus delbrueckii subsp. bulgaricus B3 strain (exopolysaccharide of 211 mg/l: high-EPS group) or Lactobacillus delbrueckii subsp. bulgaricus A13 strain (EPS of 27 mg/l: low-EPS group), which were given into the stomach. The non-colitis–fed control group was only treated with high-exopolysaccharide strain. The model-control and control groups were treated only with tap water. Rats were killed after a seven-day treatment period. Disease activity was quantified by use of histologic scores and colonic myeloperoxidase activity, which is a marker of neutrophil infiltration during inflammation. Results The enhanced inflammatory response was accompanied by a higher level of myeloperoxidase activity in the colitis group. Histologic scores of colonic damage and myeloperoxidase activity were lower in both probiotic-treated groups compared with those of the colitis control group (P < 0.001), although the mentioned scores improved significantly more in the high-EPS group than in the low-EPS group (P < 0.001). Conclusions Exopolysaccharide-producing probiotics significantly attenuate experimental colitis, which may be mediated by exopolysaccharide in a dose-dependent manner. Therefore, exopolysaccharide-producing probiotics may be a promising therapeutic role in inflammatory bowel disease. Supported in part by the Scientific and Technological Research council of Turkey (TUBITAK), TBAG-2090 (101T129) (the probiotic properties of experimental studies and the isolations of the strains used in this study).     

Indications for the use of probiotics in gastrointestinal diseases

Probiotics are live microbial organisms that are present in foods or dietary supplements and that confer health benefits to the host when ingested in sufficient quantities. Probiotics can be bacterial (e.g. Bifidobacteria spp. and Lactobacillus spp.) or yeasts (e.g. Saccharomyces boulardii). The administration of probiotics is often believed to be by and large beneficial for individuals with inflammatory or infectious diseases of the gastrointestinal tract. These positive effects are generally attributed to the ability of probiotics to regulate intestinal permeability, normalize host intestinal flora, improve gut immune barrier function, and equilibrate the balance between proinflammatory and anti-inflammatory cytokines. Of note, however, these claims are not always substantiated by findings from properly conducted clinical trials. Of particular importance, even when results from randomized controlled trials support the beneficial effects of a particular probiotic for a specific indication, the benefits achieved by the probiotic are generally not translatable to other probiotic formulations. This review discusses the gastrointestinal indications for probiotic use and describes the level of evidence that supports the use of specific probiotics for these indications. Several indications are addressed, including enteric infections, gastritis caused by Helicobacter pylori infection, necrotizing enterocolitis, inflammatory bowel diseases, and irritable bowel syndrome.     

Do synbiotics really enhance beneficial synbiotics effect on defecation symptoms in healthy adults?: Randomized,double-blind,placebo-controlled trial

Goals:We examined whether synbiotics enhance improvement by probiotics.Background:Probiotics, which are beneficial microbacteria, are a nutritional intervention for treatment of functional constipation or its tendency. Prebiotics, meanwhile, can promote the proliferation of probiotics in the gastrointestinal tract and enhance their beneficial effects. Synbiotics, a combination of probiotics and prebiotics, may be superior to probiotics in the treatment of defecation-related symptoms, but this requires elucidation.Study:This randomized, double-blind, placebo-controlled study enrolled 69 healthy adults with constipation tendency. Participants were allocated to either control, probiotics, or synbiotics groups and they recorded details of their defecations and their condition. The first 2 weeks were the observation period and the latter 2 weeks were the intervention period, in which participants took test foods. Probiotic foods included Bifidobacterium longum NT strain (10¹⁰ CFU/day), synbiotic foods included the NT strain (10¹⁰ CFU/day) and galactooligosaccharide (1 g/day). Placebo foods contained the vehicle only. Participants answered questionnaires (Patient Assessment on Constipation Symptoms [PAC-SYM], and one on dietary history) on the last day of each period.Results:Nine participants withdrew consent, and 2 of the remaining 60 had missing data. Age, body mass index, and sex were not significantly different between the 3 groups. Frequency of bowel movements in the fourth week, the primary endpoint, was not increased in the probiotics or synbiotics groups compared with the control group, and the frequency of bowel movements and days with defecation were not changed by probiotics or synbiotics during the intervention period. Probiotics and synbiotics did not improve stool conditions, although incomplete defecation was improved by probiotics but not by synbiotics compared with placebo. PAC-SYM indicated that stool condition and total scores were improved by probiotics but not by synbiotics during the intervention compared with placebo.Conclusion:The probiotic strain Bifidobacterium longum NT can improve constipation symptoms, especially stool condition, but it does not increase bowel movement frequency in healthy adults with constipation tendency. Synbiotics treatment seemed to diminish this improvement of constipation induced by probiotics. This study indicates the possibility of attenuation of beneficial effects from probiotics by the use of synbiotics, contrary to synbiotics theory.     

Probiotics for the treatment of type 2 diabetes: A review of randomized controlled trials

With the increasing prevalence of type 2 diabetes mellitus (T2DM), there is increased interest in probiotic supplementation for improving glycaemic control. This review evaluates nine randomized controlled trials that tested the effects of probiotics on glycaemic outcomes including fasting plasma glucose, fasting plasma insulin, haemoglobin A1c, and homeostatic model assessment of insulin resistance among adults with T2DM. Based on the evidence reviewed, multistrain probiotics that contain seven million to 100 billion colony forming units of Lactobacillus acidophilus, Streptococcus thermophilus, Lactobacillus bulgaricus, and/or Bifidobacterium lactis administered for 6 to 12 weeks may be efficacious for improving glycaemic control in adults with T2DM. Further research is needed to understand the role of the gut microbiota and the probiotic dose, medium, and duration of exposure that is most effective for disease management.     

Probiotics and prebiotics for gastrointestinal infections

There is growing interest in and knowledge about the potential health-promoting benefits of both probiotics and prebiotics. Multiple mechanisms of action for the beneficial effect of probiotics and prebiotics have been postulated, including prevention of pathogenic bacteria growth, production of antimicrobial agents, stimulation of mucosal barrier function, and altering immunoregulation. Clinical trials support the efficacy of probiotics in the treatment of acute infectious diarrhea, the prevention of antibiotic associated diarrhea, and the prevention of recurrent Clostridium difficile infection. Although some data support the potential benefit of probiotic therapy in traveler’s diarrhea, diverticular disease, and Helicobacter pylori, the strength of this evidence is limited. This paper will review the recent literature relevant to the mechanism of action and utility of probiotics and prebiotics in the treatment of gastrointestinal infections.     

The immunomodulatory effect of probiotics beyond atopy: an update

Background: In the past decades, the theory of “allergen avoidance” was considered the standard treatment for preventing the onset of allergic diseases. Recently, the concept of “immune tolerance” has replaced this old theory, and induction of tolerance by exposure is actually considered the appropriate method for preventing atopic diseases and other immunomediated pathologies. On the other hand, it is obvious that for public health reasons, abandoning current medical and hygienic practices is not desirable; therefore, safe alternatives, such as probiotics, have been suggested for providing necessary microbial stimulation. Objective: The purpose of our review is to describe the immunomodulatory and anti-inflammatory properties of probiotics, reporting literature data on their effect when used for the treatment of immunomediated diseases. Materials and methods: Articles reporting the evidence on the use of probiotics in immunomediated diseases, such as atopy, cow’s milk allergy and rheumatoid arthritis (RA), and in inflammatory diseases, such as inflammatory bowel diseases (IBDs), with or without statistical meta-analysis, were selected in three different search engines: (1) MEDLINE via PubMed interface, (2) Scopus and (3) Google Scholar for all articles published from inception to July 2013. Titles and abstracts of identified papers were screened by two independent reviewers to determine whether they met the eligibility criteria of interest to develop our review. Subsequently, full texts of the remaining articles were independently retrieved for eligibility by the two reviewers. Results and Discussion: The recent literature is focusing its interest towards the immunologic properties of relatively harmless organisms, including lactobacilli and bifidobacteria, helminths and saprophytic mycobacteria that may skew immune responses towards immunoregulation by inducing Treg cells, rather than eliciting a pro-inflammatory immune response. For this reason, recent researches have been addressed on the use of probiotics to promote immunoregulation in atopic diseases, such as atopic/eczema dermatitis syndrome and food allergy, as well as in inflammatory-based diseases such as IBDs, RA and bronchial asthma.     

Probiotics,infection and immunity

PURPOSE OF REVIEW: Taking live bacteria by mouth to improve health (probiotics) is not intuitively rational yet it is a practice with a long history. As interest in the effects on health of the intestinal flora has developed, along with major advances in the technology for studying it, so has come a new interest in establishing the true benefits of probiotic therapy. This review summarizes the most recent contributions to this rapidly developing area. RECENT FINDINGS: Probiotic bacteria, mainly bifidobacteria and lactobacilli for historical reasons, can prevent or ameliorate some diseases. Many empirical studies have been done, but work to develop the ideal characteristics of probiotics lags behind. Current literature covers survival of probiotics in the gut, mucosal adherence, antibacterial/pathogen mechanisms, effects on immune function and clinical studies. SUMMARY: Probiotic bacteria are effective in preventing and reducing the severity of acute diarrhoea in children. They are also useful in antibiotic associated diarrhoea but not for elimination of Helicobacter pylori. In inflammatory bowel disease, especially ulcerative colitis, probiotics offer a safe alternative to current therapy. Probiotics have been used to prevent urogenital tract infection with benefit and, perhaps more intriguingly, to reduce atopy in children. Probiotics do not invariably work and study of mechanisms is urgently needed.     

Epidemiology, Pathogenesis, and Management of Clostridium difficile Infection

Clostridium difficile infection is an important health problem worldwide and leads to increased morbidity and mortality, particularly among the elderly population. Antibiotics, especially those with a broad spectrum, often trigger the infection; hence the use of unnecessary antibiotics should be avoided. Mild to moderate cases respond to metronidazole or vancomycin. Severe cases may require bowel resection. Chronic relapsing cases require a prolonged course of antibiotics, immunoglobulin, probiotics, and, occasionally, feces enema. This review provides a comprehensive update on pathogenesis and management of Clostridium difficile infection for health professionals all over the world.