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Journal ArticleDOI

Health benefits and health claims of probiotics: bridging science and marketing

TL;DR: An open dialogue between basic and clinical scientists, regulatory authorities, food and nutrition industry, and consumers could bridge the gap between science and marketing of probiotics.
Abstract: Health claims for probiotics are evaluated by the Panel on Dietetic Products, Nutrition and Allergies of the European Food Safety Authority. Despite a substantial amount of basic and clinical research on the beneficial effects of probiotics, all of the evaluated claim applications thus far have received a negative opinion. With the restrictions on the use of clinical endpoints, validated biomarkers for gut health and immune health in relation to reduction in disease risk are needed. Clear-cut criteria for design as well as evaluation of future studies are needed. An open dialogue between basic and clinical scientists, regulatory authorities, food and nutrition industry, and consumers could bridge the gap between science and marketing of probiotics.

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Journal ArticleDOI
TL;DR: It is found that dietary guidelines commonly advocate the consumption of yoghurt or similar products, but specific comments on probiotics are rare, despite good quality evidence supporting the role of probiotics for certain health effects.
Abstract: Fermented foods have been consumed for centuries across many geographical locales and have traditionally been considered healthy foods, partly because of the live microbes contained in them. The concept of “probiotics” further requires that the microbes be defined and their health effects be demonstrated through human intervention studies or other suitable investigations before marketing with corresponding health messages. Here, we review recommendations for fermented foods and probiotics in several countries outside the EU, focusing on food-based dietary guidelines. We emphasize recommendations on yoghurt and probiotics made by expert bodies. We found that dietary guidelines commonly advocate the consumption of yoghurt or similar products, but specific comments on probiotics are rare. Further, we reviewed guidelines from clinical associations. In general, they acknowledge the beneficial effects of probiotics, but often suggest the need for further research. This is true despite good quality evidence supporting the role of probiotics for certain health effects, such as prevention of eczema in infants, management of side effects from antibiotics and alleviation of functional bowel symptoms. Additional research to support future dietary recommendations should focus on determining effect size, identifying responders and non-responders, clarifying strain-specificity of effects and confirming mechanisms.

51 citations

Journal ArticleDOI
TL;DR: The clinical effectiveness and side effects of probiotics used alone or combined with other agents for prevention or treatment of chemotherapy- or radiotherapy-related diarrhoea in people with cancer are evaluated.
Abstract: Background: Treament-related diarrhoea is one of the most common and troublesome adverse effects related to chemotherapy or radiotherapy in people with cancer. Its reported incidence has been as high as 50% to 80%. Severe treatment-related diarrhoea can lead to fluid and electrolyte losses and nutritional deficiencies and could adversely affect quality of life (QoL). It is also associated with increased risk of infection in people with neutropenia due to anticancer therapy and often leads to treatment delays, dose reductions, or treatment discontinuation. Probiotics may be effective in preventing or treating chemotherapy- or radiotherapy-induced diarrhoea. Objectives: To evaluate the clinical effectiveness and side effects of probiotics used alone or combined with other agents for prevention or treatment of chemotherapy- or radiotherapy-related diarrhoea in people with cancer. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 7), MEDLINE (1946 to July week 2, 2017), and Embase (1980 to 2017, week 30). We also searched prospective clinical trial registers and the reference lists of included studies. Selection criteria: We included randomised controlled trials (RCTs) investigating the effects of probiotics for prevention or treatment of chemotherapy- or radiotherapy-related diarrhoea in people with cancer. Data collection and analysis: Two review authors independently selected studies, extracted data, and assessed risk of bias. We used random-effects models for all meta-analyses. If meta-analysis was not possible, we summarised the results narratively. Main results: We included 12 studies involving 1554 participants. Eleven studies were prevention studies, of which seven compared probiotics with placebo (887 participants), one compared two doses of probiotics with each other and with placebo (246 participants), and three compared probiotics with another active agent (216 participants).The remaining study assessed the effectiveness of probiotics compared with placebo for treatment of radiotherapy-related diarrhoea (205 participants). For prevention of radiotherapy (with or without chemotherapy)-induced diarrhoea, review authors identified five heterogeneous placebo-controlled studies (with 926 participants analysed). Owing to heterogeneity, we could not carry out a meta-analysis, except for two outcomes. For occurrence of any diarrhoea, risk ratios (RRs) ranged from 0.35 (95% confidence interval (CI) 0.26 to 0.47) to 1.0 (95% CI 0.94 to 1.06) (three studies; low-certainty evidence). A beneficial effect of probiotics on quality of life could neither be demonstrated nor refuted (two studies; low-certainty evidence). For occurrence of grade 2 or higher diarrhoea, the pooled RR was 0.75 (95% CI 0.55 to 1.03; four studies; 420 participants; low-certainty evidence), and for grade 3 or higher diarrhoea, RRs ranged from 0.11 (95% CI 0.06 to 0.23) to 1.24 (95% CI 0.74 to 2.08) (three studies; low-certainty evidence). For probiotic users, time to rescue medication was 36 hours longer in one study (95% CI 34.7 to 37.3), but another study reported no difference (moderate-certainty evidence). For the need for rescue medication, the pooled RR was 0.50 (95% CI 0.15 to 1.66; three studies; 194 participants; very low-certainty evidence). No study reported major differences between groups with respect to adverse effects. Although not mentioned explicitly, no studies reported deaths, except one in which one participant in the probiotics group died of myocardial infarction after three sessions of radiotherapy. Three placebo-controlled studies, with 128 analysed participants, addressed prevention of chemotherapy-induced diarrhoea. For occurrence of any diarrhoea, the pooled RR was 0.59 (95% CI 0.36 to 0.96; two studies; 106 participants; low-certainty evidence). For all other outcomes, a beneficial effect of probiotics could be neither demonstrated nor refuted (one to two studies; 46 to 106 participants; all low-certainty evidence). Studies did not address quality of life nor time to rescue medication. Three studies compared probiotics with another intervention in 213 participants treated with radiotherapy (with or without chemotherapy). One very small study (21 participants) reported less diarrhoea six weeks after treatment when dietary counselling was provided (RR 0.30, 95% CI 0.11 to 0.81; very low-certainty evidence). In another study (148 participants), grade 3 or 4 diarrhoea occurred less often in the probiotics group than in the control group (guar gum containing nutritional supplement) (odds ratio (OR) 0.38, 95% CI 0.16 to 0.89; low-certainty evidence), and two studies (63 participants) found less need for rescue medication of probiotics versus another active treatment (RR 0.44, 95% CI 0.22 to 0.86; very low-certainty evidence). Studies did not address quality of life nor time to rescue medication. One placebo-controlled study with 205 participants addressed treatment for radiotherapy-induced diarrhoea and could not demonstrate or refute a beneficial effect of probiotics on average diarrhoea grade, time to rescue medication for diarrhoea (13 hours longer in the probiotics group; 95% CI -0.9 to 26.9 hours), or need for rescue medication (RR 0.74, 95% CI 0.53 to 1.03; moderate-certainty evidence). This study did not address quality of life. No studies reported serious adverse events or diarrhoea-related deaths. Authors' conclusions: This review presents limited low- or very low-certainty evidence supporting the effects of probiotics for prevention and treatment of diarrhoea related to radiotherapy (with or without chemotherapy) or chemotherapy alone, need for rescue medication, or occurrence of adverse events. All studies were underpowered and heterogeneous. Severe side effects were absent from all studies. Robust evidence on this topic must be provided by future methodologically well-designed trials.

49 citations

Book ChapterDOI
13 Jul 2016
TL;DR: There is a clear need for more elaborate assays that would better represent the complex interactions between the probiotics and the final host, and replacement alternative methods, for example incorporating human cells and tissues, avoids such confounding variables.
Abstract: The antimicrobial or antagonistic activity of probiotics is an important property that includes the production of antimicrobial compounds, competitive exclusion of pathogens, enhancement of the intestinal barrier function and others. There are many methods to ascertain probiotic properties, including various in vitro and in vivo methods. The in vivo methods include various modifications of the spot‐on lawn assay, agar well diffusion assay (AWDA), co‐culturing methods, usage of cell lines and others. In many cases in vitro antagonist activity is observed, but in real settings it is not observed. The in vivo methods mainly used are animal models; however, their use is being restricted according to the European legislation OJ L136. The justification of animal models is also questionable as the results of studies on animals do not predict the same results for humans. The use of replacement alternative methods, for example incorporating human cells and tissues, avoids such confounding variables. Most important studies are double‐ blinded randomized clinical trials; however, these studies are difficult to perform as it is not easy to achieve uniform conditions. There is a clear need for more elaborate assays that would better represent the complex interactions between the probiotics and the final host. This complex situation is a challenge for scientists.

46 citations


Cites background from "Health benefits and health claims o..."

  • ...It is estimated that there are 100 trillion microorganisms in the intestine of a human adult and this is 10 times larger than the number of cells in the human body [1, 2]....

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Journal ArticleDOI
TL;DR: Factors from culture preparation and preservation, conditions in consumer product matrices, and genetic, dietary, cultural, and health differences between consumers can affect probiotic cell activity and probably influence the specific host-microbe interactions required for probiotic effects in the digestive tract.

45 citations

Journal ArticleDOI
TL;DR: Advances in molecular sequencing and microbiology have shed light on the importance of the human microbiota in development, health, and disease and suggest that probiotic-based therapies have considerable potential to exploit host-microbe relationships and improve clinical outcomes.
Abstract: Background:Microorganisms living throughout the body comprise the human “microbiota” and play an important role in health and disease. Recent research suggests that alterations in the skin microbiota may underlie chronic wound pathology. Probiotics are bacteria or yeast that confer a health benefit

45 citations

References
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Journal ArticleDOI
04 Mar 2010-Nature
TL;DR: The Illumina-based metagenomic sequencing, assembly and characterization of 3.3 million non-redundant microbial genes, derived from 576.7 gigabases of sequence, from faecal samples of 124 European individuals are described, indicating that the entire cohort harbours between 1,000 and 1,150 prevalent bacterial species and each individual at least 160 such species.
Abstract: To understand the impact of gut microbes on human health and well-being it is crucial to assess their genetic potential. Here we describe the Illumina-based metagenomic sequencing, assembly and characterization of 3.3 million non-redundant microbial genes, derived from 576.7 gigabases of sequence, from faecal samples of 124 European individuals. The gene set, ~150 times larger than the human gene complement, contains an overwhelming majority of the prevalent (more frequent) microbial genes of the cohort and probably includes a large proportion of the prevalent human intestinal microbial genes. The genes are largely shared among individuals of the cohort. Over 99% of the genes are bacterial, indicating that the entire cohort harbours between 1,000 and 1,150 prevalent bacterial species and each individual at least 160 such species, which are also largely shared. We define and describe the minimal gut metagenome and the minimal gut bacterial genome in terms of functions present in all individuals and most bacteria, respectively

9,268 citations


"Health benefits and health claims o..." refers background in this paper

  • ...For the fifty-seven most common bacterial species identified by metagenome sequence analysis in the human gut, the inter-individual variability of abundance is between 12- and 2187-fold((16))....

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  • ...However, a clearly distinct composition of gut microbiota, both compared with healthy individuals and between the two diseases, is found in inflammatory bowel disease (ulcerative colitis and Crohn’s disease)((16))....

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Journal ArticleDOI
29 May 2008-Nature
TL;DR: It is reported here that the prominent human symbiont Bacteroides fragilis protects animals from experimental colitis induced by Helicobacter hepaticus and that molecules of the bacterial microbiota can mediate the critical balance between health and disease.
Abstract: Humans are colonized by multitudes of commensal organisms representing members of five of the six kingdoms of life; however, our gastrointestinal tract provides residence to both beneficial and potentially pathogenic microorganisms. Imbalances in the composition of the bacterial microbiota, known as dysbiosis, are postulated to be a major factor in human disorders such as inflammatory bowel disease. We report here that the prominent human symbiont Bacteroides fragilis protects animals from experimental colitis induced by Helicobacter hepaticus, a commensal bacterium with pathogenic potential. This beneficial activity requires a single microbial molecule (polysaccharide A, PSA). In animals harbouring B. fragilis not expressing PSA, H. hepaticus colonization leads to disease and pro-inflammatory cytokine production in colonic tissues. Purified PSA administered to animals is required to suppress pro-inflammatory interleukin-17 production by intestinal immune cells and also inhibits in vitro reactions in cell cultures. Furthermore, PSA protects from inflammatory disease through a functional requirement for interleukin-10-producing CD4+ T cells. These results show that molecules of the bacterial microbiota can mediate the critical balance between health and disease. Harnessing the immunomodulatory capacity of symbiosis factors such as PSA might potentially provide therapeutics for human inflammatory disorders on the basis of entirely novel biological principles.

2,097 citations


"Health benefits and health claims o..." refers background in this paper

  • ...In a series of landmark publications((7,19,20)), Dennis Kasper’s group has demonstrated that the capsular polysaccharide polysaccharide A of Bacteroides fragilis is indispensable for normal development of mucosal T lymphocytes and control of exper-...

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  • ...Unfortunately, with a few exceptions((7,8)), the genes that determine or underlie the health benefit delivered by specific probiotic strains have not been identified to date....

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Journal ArticleDOI
17 May 2010-PLOS ONE
TL;DR: Evidence is provided for the fact that the ageing process deeply affects the structure of the human gut microbiota, as well as its homeostasis with the host's immune system, because of its crucial role in the host physiology and health status.
Abstract: Background: Age-related physiological changes in the gastrointestinal tract, as well as modifications in lifestyle, nutritional behaviour, and functionality of the host immune system, inevitably affect the gut microbiota, resulting in a greater susceptibility to infections. Methodology/Principal Findings: By using the Human Intestinal Tract Chip (HITChip) and quantitative PCR of 16S rRNA genes of Bacteria and Archaea, we explored the age-related differences in the gut microbiota composition among young adults, elderly, and centenarians, i.e subjects who reached the extreme limits of the human lifespan, living for over 100 years. We observed that the microbial composition and diversity of the gut ecosystem of young adults and seventy-years old people is highly similar but differs significantly from that of the centenarians. After 100 years of symbiotic association with the human host, the microbiota is characterized by a rearrangement in the Firmicutes population and an enrichment in facultative anaerobes, notably pathobionts. The presence of such a compromised microbiota in the centenarians is associated with an increased inflammatory status, also known as inflammageing, as determined by a range of peripheral blood inflammatory markers. This may be explained by a remodelling of the centenarians’ microbiota, with a marked decrease in Faecalibacterium prauznitzii and relatives, symbiotic species with reported anti-inflammatory properties. As signature bacteria of the long life we identified specifically Eubacterium limosum and relatives that were more than ten-fold increased in the centenarians. Conclusions/Significance: We provide evidence for the fact that the ageing process deeply affects the structure of the human gut microbiota, as well as its homeostasis with the host’s immune system. Because of its crucial role in the host physiology and health status, age-related differences in the gut microbiota composition may be related to the progression of diseases and frailty in the elderly population.

1,180 citations


"Health benefits and health claims o..." refers background in this paper

  • ...Moreover, the intestinal microbiota also changes in time as was illustrated recently in a study, in which age groups up to 100 years were compared((17))....

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Journal ArticleDOI
TL;DR: The nonclassic actions of vitamin D are cell specific and provide a number of potential new clinical applications for 1,25(OH)(2)D(3) and its analogs, however, the use ofitamin D metabolites and analogs for these applications remains limited by the classic actions of Vitamin D leading to hypercalcemia and hypercalcuria.
Abstract: Context: Vitamin D receptors are found in most tissues, not just those participating in the classic actions of vitamin D such as bone, gut, and kidney. These nonclassic tissues are therefore potential targets for the active metabolite of vitamin D, 1,25(OH)2D. Furthermore, many of these tissues also contain the enzyme CYP27B1 capable of producing 1,25(OH)2D from the circulating form of vitamin D. This review was intended to highlight the actions of 1,25(OH)2D in several of these tissues but starts with a review of vitamin D production, metabolism, and molecular mechanism. Evidence Acquisition: Medline was searched for articles describing actions of 1,25(OH)2D on parathyroid hormone and insulin secretion, immune responses, keratinocytes, and cancer. Evidence Synthesis: Vitamin D production in the skin provides an efficient source of vitamin D. Subsequent metabolism to 1,25(OH)2D within nonrenal tissues differs from that in the kidney. Although vitamin D receptor mediates the actions of 1,25(OH)2D, regulati...

882 citations

Journal ArticleDOI
TL;DR: This Review highlights the documented signalling interactions of the surface molecules of probiotic bacteria (such as long surface appendages, polysaccharides and lipoteichoic acids) with PRRs with respect to host pattern recognition receptors of the gastrointestinal mucosa.
Abstract: Interactions between host cell receptors and the surface molecules of bacteria are important determinants of the nature of the relationship between the two organisms. In this Review, Lebeer, Vanderleyden and De Keersmaecker examine the signalling interactions of probiotic bacterial cell surface molecules. How can probiotic bacteria transduce their health benefits to the host? Bacterial cell surface macromolecules are key factors in this beneficial microorganism–host crosstalk, as they can interact with host pattern recognition receptors (PRRs) of the gastrointestinal mucosa. In this Review, we highlight the documented signalling interactions of the surface molecules of probiotic bacteria (such as long surface appendages, polysaccharides and lipoteichoic acids) with PRRs. Research on host–probiotic interactions can benefit from well-documented host–microorganism studies that span the spectrum from pathogenicity to mutualism. Distinctions and parallels are therefore drawn with the interactions of similar molecules that are presented by gastrointestinal commensals and pathogens.

852 citations


"Health benefits and health claims o..." refers background in this paper

  • ...For a number of strains, it has been demonstrated now that the probiotic bacteria can bind to receptors on cells of the immune system including dendritic cells((27))....

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