Safety aspects and implications of regulation of probiotic bacteria in food and food supplements. - Related Documents




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422501.0000Safety aspects and implications of regulation of probiotic bacteria in food and food supplements. The application of living bacteria as probiotics in food or food supplements requires a careful safety assessment. This review summarizes key issues concerning the safety aspects of bacteria added to particular products marketed for improvement of general health or treatment of (post)infectious symptoms. The bacteria used in such products should be completely safe; however, it can be challenging to provide evidence for absence of all virulence properties. In some cases, virulence factors have been detected in probiotic bacterial strains, and the implications of these traits for safety assessments are discussed. Horizontal gene transfer can result in acquisition of virulence genes or antimicrobial resistance in probiotic bacteria. Antimicrobial resistance in these bacteria can possibly aid the spread of undesired resistance in intestinal bacterial populations. The relative risk of such gene transfers is considered. The generation of complete bacterial genome sequences can both resolve and create safety issues. Current practices of safety assessment procedures in the United States and the European Union are briefly reviewed and a future outlook is provided.200818724773
422610.9999Assessing the Risk of Probiotic Dietary Supplements in the Context of Antibiotic Resistance. Probiotic bacteria are known to harbor intrinsic and mobile genetic elements that confer resistance to a wide variety of antibiotics. Their high amounts in dietary supplements can establish a reservoir of antibiotic resistant genes in the human gut. These resistant genes can be transferred to pathogens that share the same intestinal habitat thus resulting in serious clinical ramifications. While antibiotic resistance of probiotic bacteria from food, human and animal sources have been well-documented, the resistant profiles of probiotics from dietary supplements have only been recently studied. These products are consumed with increasing regularity due to their health claims that include the improvement of intestinal health and immune response as well as prevention of acute and antibiotic-associated diarrhea and cancer; but, a comprehensive risk assessment on the spread of resistant genes to human health is lacking. Here, we highlight recent reports of antibiotic resistance of probiotic bacteria isolated from dietary supplements, and propose complementary strategies that can shed light on the risks of consuming such products in the context of a global widespread of antibiotic resistance. In concomitant with a broader screening of antibiotic resistance in probiotic supplements is the use of computational simulations, live imaging and functional genomics to harvest knowledge on the evolutionary behavior, adaptations and dynamics of probiotics studied in conditions that best represent the human gut including in the presence of antibiotics. The underlying goal is to enable the health benefits of probiotics to be exploited in a responsible manner and with minimal risk to human health.201728579981
423120.9999Recent investigations and updated criteria for the assessment of antibiotic resistance in food lactic acid bacteria. The worldwide use, and misuse, of antibiotics for about sixty years in the so-called antibiotic era, has been estimated in some one to ten million tons, a relevant part of which destined for non-therapeutic purposes such as growth promoting treatments for livestock or crop protection. As highly adaptable organisms, bacteria have reacted to this dramatic change in their environment by developing several well-known mechanisms of antibiotic resistance and are becoming increasingly resistant to conventional antibiotics. In recent years, commensal bacteria have become a cause of concern since they may act as reservoirs for the antibiotic resistance genes found in human pathogens. In particular, the food chain has been considered the main route for the introduction of animal and environment associated antibiotic resistant bacteria into the human gastrointestinal tract (GIT) where these genes may be transferred to pathogenic and opportunistic bacteria. As fundamental microbial communities in a large variety of fermented foods and feed, the anaerobe facultative, aerotolerant lactic acid bacteria (LAB) are likely to play a pivotal role in the resistance gene exchange occurring in the environment, food, feed and animal and human GIT. Therefore their antibiotic resistance features and their genetic basis have recently received increasing attention. The present article summarises the results of the latest studies on the most typical genera belonging to the low G + C branch of LAB. The evolution of the criteria established by European regulatory bodies to ensure a safe use of microorganisms in food and feed, including the assessment of their antibiotic resistance is also reviewed.201121515393
422730.9999Antibiotic resistance determinants in the interplay between food and gut microbiota. A complex and heterogeneous microflora performs sugar and lactic acid fermentations in food products. Depending on the fermentable food matrix (dairy, meat, vegetable etc.) as well as on the species composition of the microbiota, specific combinations of molecules are produced that confer unique flavor, texture, and taste to each product. Bacterial populations within such "fermented food microbiota" are often of environmental origin, they persist alive in foods ready for consumption, eventually reaching the gastro-intestinal tract where they can interact with the resident gut microbiota of the host. Although this interaction is mostly of transient nature, it can greatly contribute to human health, as several species within the food microbiota also display probiotic properties. Such an interplay between food and gut microbiota underlines the importance of the microbiological quality of fermented foods, as the crowded environment of the gut is also an ideal site for genetic exchanges among bacteria. Selection and spreading of antibiotic resistance genes in foodborne bacteria has gained increasing interest in the past decade, especially in light of the potential transferability of antibiotic resistance determinants to opportunistic pathogens, natural inhabitants of the human gut but capable of acquiring virulence in immunocompromised individuals. This review aims at describing major findings and future prospects in the field, especially after the use of antibiotics as growth promoters was totally banned in Europe, with special emphasis on the application of genomic technologies to improve quality and safety of fermented foods.201121526400
422440.9999The Genus Enterococcus: Between Probiotic Potential and Safety Concerns-An Update. A considerable number of strains belonging to different species of Enterococcus are highly competitive due to their resistance to wide range of pH and temperature. Their competitiveness is also owed to their ability to produce bacteriocins recognized for their wide-range effectiveness on pathogenic and spoilage bacteria. Enterococcal bacteriocins have attracted great research interest as natural antimicrobial agents in the food industry, and as a potential drug candidate for replacing antibiotics in order to treat multiple drugs resistance pathogens. However, the prevalence of virulence factors and antibiotic-resistance genes and the ability to cause disease could compromise their application in food, human and animal health. From the current regulatory point of view, the genus Enterococcus is neither recommended for the QPS list nor have GRAS status. Although recent advances in molecular biology and the recommended methods for the safety evaluation of Enterococcus strains allowed the distinction between commensal and clinical clades, development of highly adapted methods and legislations are still required. In the present review, we evaluate some aspects of Enterococcus spp. related to their probiotic properties and safety concerns as well as the current and potential application in food systems and treatment of infections. The regulatory status of commensal Enterococcus candidates for food, feed, probiotic use, and recommended methods to assess and ensure their safety are also discussed.201830123208
423050.9999Antibiotic resistance in food lactic acid bacteria--a review. Antibiotics are a major tool utilized by the health care industry to fight bacterial infections; however, bacteria are highly adaptable creatures and are capable of developing resistance to antibiotics. Consequently, decades of antibiotic use, or rather misuse, have resulted in bacterial resistance to many modern antibiotics. This antibiotic resistance can cause significant danger and suffering for many people with common bacterial infections, those once easily treated with antibiotics. For several decades studies on selection and dissemination of antibiotic resistance have focused mainly on clinically relevant species. However, recently many investigators have speculated that commensal bacteria including lactic acid bacteria (LAB) may act as reservoirs of antibiotic resistance genes similar to those found in human pathogens. The main threat associated with these bacteria is that they can transfer resistance genes to pathogenic bacteria. Genes conferring resistance to tetracycline, erythromycin and vancomycin have been detected and characterized in Lactococcus lactis, Enterococci and, recently, in Lactobacillus species isolated from fermented meat and milk products. A number of initiatives have been recently launched by various organizations across the globe to address the biosafety concerns of starter cultures and probiotic microorganisms. The studies can lead to better understanding of the role played by the dairy starter microorganisms in horizontal transfer of antibiotic resistance genes to intestinal microorganisms and food-associated pathogenic bacteria.200516289406
945460.9999A critical review of antibiotic resistance in probiotic bacteria. Probiotics are defined as live microorganisms that, when administered in adequate amounts, confer a health benefit upon the host. At present, probiotics are gaining popularity worldwide and are widely used in food and medicine. Consumption of probiotics is increasing with further in-depth research on the relationship between intestinal flora and host health. Most people pay more attention to the function of probiotics but ignore their potential risks, such as infection and antibiotic resistance transfer to pathogenic microbes. Physiological functions, effects and mechanisms of action of probiotics were covered in this review, as well as the antibiotic resistance phenotypes, mechanisms and genes found in probiotics. Typical cases of antibiotic resistance of probiotics were also highlighted, as well as the potential risks (including pathogenicity, infectivity and excessive immune response) and corresponding strategies (dosage, formulation, and administration route). This timely study provides an avenue for further research, development and application of probiotics.202032846610
663770.9999Antibiotic Resistance Gene Expression in Veterinary Probiotics: Two Sides of the Coin. The rapid proliferation of antimicrobial resistance has emerged as one of the most pressing animal and public health challenges of our time. Probiotics, extensively employed in human and veterinary medicine, are instrumental in maintaining a balanced microbiome and mitigating its disruption during antibiotic therapy. While their numerous benefits are well documented, probiotics also present potential risks, notably the capacity to harbor antimicrobial resistance genes. This genetic reservoir could contribute to the emergence and spread of antimicrobial resistance by facilitating the horizontal transfer of resistance genes to pathogenic bacteria within the gut. This review critically examines the presence of antimicrobial resistance genes in commonly used probiotic strains, explores the underlying mechanisms of resistance, and provides a balanced analysis of the benefits and risks associated with their use. By addressing these dual aspects, this paper highlights the need for vigilant evaluation of probiotics to preserve their therapeutic potential while minimizing public health risks.202540266902
422380.9999Use of Probiotic Bacteria and Bacteriocins as an Alternative to Antibiotics in Aquaculture. In addition to their use in human medicine, antimicrobials are also used in food animals and aquaculture, and their use can be categorized as therapeutic against bacterial infections. The use of antimicrobials in aquaculture may involve a broad environmental application that affects a wide variety of bacteria, promoting the spread of bacterial resistance genes. Probiotics and bacteriocins, antimicrobial peptides produced by some types of lactic acid bacteria (LAB), have been successfully tested in aquatic animals as alternatives to control bacterial infections. Supplementation might have beneficial impacts on the intestinal microbiota, immune response, development, and/or weight gain, without the issues associated with antibiotic use. Thus, probiotics and bacteriocins represent feasible alternatives to antibiotics. Here, we provide an update with respect to the relevance of aquaculture in the animal protein production sector, as well as the present and future challenges generated by outbreaks and antimicrobial resistance, while highlighting the potential role of probiotics and bacteriocins to address these challenges. In addition, we conducted data analysis using a simple linear regression model to determine whether a linear relationship exists between probiotic dose added to feed and three variables of interest selected, including specific growth rate, feed conversion ratio, and lysozyme activity.202236144306
422090.9999Whole genome sequencing for the risk assessment of probiotic lactic acid bacteria. Probiotic bacteria exhibit beneficial effects on human and/or animal health, and have been widely used in foods and fermented products for decades. Most probiotics consist of lactic acid bacteria (LAB), which are used in the production of various food products but have also been shown to have the ability to prevent certain diseases. With the expansion of applications for probiotic LAB, there is an increasing concern with regard to safety, as cases with adverse effects, i.e., severe infections, transfer of antimicrobial resistance genes, etc., can occur. Currently, in vitro assays remain the primary way to assess the properties of LAB. However, such methodologies are not meeting the needs of strain risk assessment on a high-throughput scale, in the context of the evolving concept of food safety. Analyzing the complete genetic information, including potential virulence genes and other determinants with a negative impact on health, allows for assessing the safe use of the product, for which whole-genome sequencing (WGS) of individual LAB strains can be employed. Genomic data can also be used to understand subtle differences in the strain level important for beneficial effects, or protect patents. Here, we propose that WGS-based bioinformatics analyses are an ideal and cost-effective approach for the initial in silico microbial risk evaluation, while the technique may also increase our understanding of LAB strains for food safety and probiotic property evaluation.202335694810
4197100.9999Antibiotic-resistant bacteria: a challenge for the food industry. Antibiotic-resistant bacteria were first described in the 1940s, but whereas new antibiotics were being discovered at a steady rate, the consequences of this phenomenon were slow to be appreciated. At present, the paucity of new antimicrobials coming into the market has led to the problem of antibiotic resistance fast escalating into a global health crisis. Although the selective pressure exerted by the use of antibiotics (particularly overuse or misuse) has been deemed the major factor in the emergence of bacterial resistance to these antimicrobials, concerns about the role of the food industry have been growing in recent years and have been raised at both national and international levels. The selective pressure exerted by the use of antibiotics (primary production) and biocides (e.g., disinfectants, food and feed preservatives, or decontaminants) is the main driving force behind the selection and spread of antimicrobial resistance throughout the food chain. Genetically modified (GM) crops with antibiotic resistance marker genes, microorganisms added intentionally to the food chain (probiotic or technological) with potentially transferable antimicrobial resistance genes, and food processing technologies used at sub-lethal doses (e.g., alternative non-thermal treatments) are also issues for concern. This paper presents the main trends in antibiotic resistance and antibiotic development in recent decades, as well as their economic and health consequences, current knowledge concerning the generation, dissemination, and mechanisms of antibacterial resistance, progress to date on the possible routes for emergence of resistance throughout the food chain and the role of foods as a vehicle for antibiotic-resistant bacteria. The main approaches to prevention and control of the development, selection, and spread of antibacterial resistance in the food industry are also addressed.201323035919
9455110.9999Prospects and Challenges of Bacteriophage Substitution for Antibiotics in Livestock and Poultry Production. The overuse and misuse of antibiotics in the livestock and poultry industry has led to the development of multi-drug resistance in animal pathogens, and antibiotic resistance genes (ARGs) in bacteria transfer from animals to humans through the consumption of animal products, posing a serious threat to human health. Therefore, the use of antibiotics in livestock production has been strictly controlled. As a result, bacteriophages have attracted increasing research interest as antibiotic alternatives, since they are natural invaders of bacteria. Numerous studies have shown that dietary bacteriophage supplementation could regulate intestinal microbial composition, enhance mucosal immunity and the physical barrier function of the intestinal tract, and play an important role in maintaining intestinal microecological stability and normal body development of animals. The effect of bacteriophages used in animals is influenced by factors such as species, dose, and duration. However, as a category of mobile genetic elements, the high frequency of gene exchange of bacteriophages also poses risks of transmitting ARGs among bacteria. Hence, we summarized the mechanism and efficacy of bacteriophage therapy, and highlighted the feasibility and challenges of bacteriophage utilization in farm animal production, aiming to provide a reference for the safe and effective application of bacteriophages as an antibiotic alternative in livestock and poultry.202438248459
9451120.9999Assessing the Antibiotic Resistance in Food Lactic Acid Bacteria: Risks in the Era of Widespread Probiotic Use. Antibiotic resistance (AR) in lactic acid bacteria (LAB) has become an emerging concern in the probiotic and food industries. LAB, a key component of the human microbiota and widely used in probiotic products, can harbor antibiotic resistance genes (ARGs), which may transfer to pathogenic microorganisms. This review provides an updated overview of AR in LAB, outlining mechanisms of resistance, both intrinsic and acquired, and their implications for probiotics. Recent studies have reported the presence of resistant LAB strains in food products, highlighting the need for stringent monitoring and regulatory measures. Additionally, the review addresses the declining production of new antibiotics, exacerbating the AR crisis. Advances in bioinformatics offer powerful tools for predicting and identifying ARGs in LAB, providing powerful tools to combat this issue. We also discuss strategies to mitigate AR in LAB, such as the use of nanotechnology, combination therapy, bacteriocins, and the potential role of CRISPR and other genome editing tools.202540755505
9452130.9999Bacteriophages in the Control of Aeromonas sp. in Aquaculture Systems: An Integrative View. Aeromonas species often cause disease in farmed fish and are responsible for causing significant economic losses worldwide. Although vaccination is the ideal method to prevent infectious diseases, there are still very few vaccines commercially available in the aquaculture field. Currently, aquaculture production relies heavily on antibiotics, contributing to the global issue of the emergence of antimicrobial-resistant bacteria and resistance genes. Therefore, it is essential to develop effective alternatives to antibiotics to reduce their use in aquaculture systems. Bacteriophage (or phage) therapy is a promising approach to control pathogenic bacteria in farmed fish that requires a heavy understanding of certain factors such as the selection of phages, the multiplicity of infection that produces the best bacterial inactivation, bacterial resistance, safety, the host's immune response, administration route, phage stability and influence. This review focuses on the need to advance phage therapy research in aquaculture, its efficiency as an antimicrobial strategy and the critical aspects to successfully apply this therapy to control Aeromonas infection in fish.202235203766
4077140.9999Antimicrobial resistance and its association with tolerance to heavy metals in agriculture production. Antimicrobial resistance is a recognized public health challenge that since its emergence limits the therapeutic options available to veterinarians and clinicians alike, when treatment is warranted. This development is further compounded by the paucity of new antibiotics. The agri-food industry benefits from the availability of antimicrobial compounds for food-animal production and crop protection. Nonetheless, their improper use can result in the selection for bacteria that are phenotypically resistant to these compounds. Another class of agents used in agriculture includes various cationic metals that can be included in animal diets as nutritional supplements or spread on pastures to support crop growth and protection. Heavy metals, in particular, are giving rise to concerns among public health professionals, as they can persist in the environment remaining stable for prolonged periods. Moreover, bacteria can also exhibit resistance to these chemical elements and the genes encoding this phenotype can be physically localized to plasmids that may also contain one or more antimicrobial resistance-encoding gene(s). This paper reviews our current understanding of the role that bacteria play in expressing resistance to heavy metals. It will describe how heavy metals are used in agri-food production, and explore evidence available to link resistance to heavy metals and antimicrobial compounds. In addition, possible solutions to reduce the impact of heavy metal resistance are also discussed, including using organic minerals and reducing the level of trace minerals in animal feed rations.201728213031
4219150.9999Antibiotic resistance and virulence factors in lactobacilli: something to carefully consider. Lactobacilli are a ubiquitous bacteria, that includes many species commonly found as part of the human microbiota, take part in the natural food fermentation processes, are used as probiotics, and in the food sector as starter cultures or bio-protectors. Their wide use is dictated by a long history of safe employ, which has allowed them to be classified as GRAS (General Recognized As Safe) microorganisms by the US Food and Drug Administration (FDA) and QPS (Qualified Presumption of Safety) by the European Food Safety Authority (EFSA, 2007; EFSA, 2021). Despite their classification as safe microorganisms, several studies show that some members of Lactobacillus genus can cause, especially in individuals with previous pathological conditions, problems such as bacteremia, endocarditis, and peritonitis. In other cases, the presence of virulence genes and antibiotic resistance, and its potential transfer to pathogenic microorganisms constitute a risk to be considered. Consequently, their safety status was sometimes questioned, and it is, therefore, essential to carry out appropriate assessments before their use for any purposes. The following review focuses on the state of the art of studies on genes that confer virulence factors, including antibiotic resistance, reported in the literature within the lactobacilli, defining their genetic basis and related functions.202235082060
4195160.9999Vancomycin drug resistance, an emerging threat to animal and public health. The need to supply quality food for the growing human population has led to the revolutionization of food production and processing in recent years. Meanwhile, food production sources are at risk of microbial attack, while the use of antibiotics to counter them is posing another threat to food safety and security. Vancomycin was used as the first line of defense against multiple drug-resistant bacteria salient of which is methicillin-resistant S. aureus. The emergence of the vancomycin resistance gene in bacteria impairs the efficacy of antibiotics on the one hand while its harmful residues impart food safety concerns on the other. Currently, a novel set of resistance genes "Van cluster" is circulating in a wider range of bacteria. Considerable economic losses in terms of low production and food safety are associated with this emerging resistance. The current review focuses on the emergence of vancomycin resistance and its impact on food safety. The review proposes the need for further research on the probable routes, mechanisms, and implications of vancomycin resistance from animals to humans and vice versa.202236387389
4189170.9999Antimicrobial resistance at farm level. Bacteria that are resistant to antimicrobials are widespread. This article reviews the distribution of resistant bacteria in farm environments. Humans, animals, and environmental sites are all reservoirs of bacterial communities that contain some bacteria that are susceptible to antimicrobials and others that are resistant. Farm ecosystems provide an environment in which resistant bacteria and genes can emerge, amplify and spread. Dissemination occurs via the food chain and via several other pathways. Ecological, epidemiological, molecular and mathematical approaches are being used to study the origin and expansion of the resistance problem and its relationship to antibiotic usage. The prudent and responsible use of antibiotics is an essential part of an ethical approach to improving animal health and food safety. The responsible use of antibiotics during research is vital, but to fully contribute to the containment of antimicrobial resistance 'prudent use' must also be part of good management practices at all levels of farm life.200617094710
6638180.9999Addressing the Antibiotic Resistance Problem with Probiotics: Reducing the Risk of Its Double-Edged Sword Effect. Antibiotic resistance is a global public health problem that requires our attention. Indiscriminate antibiotic use is a major contributor in the introduction of selective pressures in our natural environments that have significantly contributed in the rapid emergence of antibiotic-resistant microbial strains. The use of probiotics in lieu of antibiotic therapy to address certain health conditions in both animals and humans may alleviate these antibiotic-mediated selective pressures. Probiotic use is defined as the actual application of live beneficial microbes to obtain a desired outcome by preventing diseased state or improving general health. Multiple studies have confirmed the beneficial effects of probiotic use in the health of both livestock and humans. As such, probiotics consumption is gaining popularity worldwide. However, concerns have been raised in the use of some probiotics strains that carry antibiotic resistance genes themselves, as they have the potential to pass the antibiotic resistance genes to pathogenic bacteria through horizontal gene transfer. Therefore, with the current public health concern on antibiotic resistance globally, in this review, we underscore the need to screen probiotic strains that are used in both livestock and human applications to assure their safety and mitigate their potential in significantly contributing to the spread of antibiotic resistance genes in our natural environments.201628018315
9681190.9999Uses of antimicrobials in plant agriculture. Bacterial diseases of plants are less prevalent than diseases caused by fungi and viruses. Antimicrobials for prophylactic treatment of bacterial diseases of plants are limited in availability, use, and efficacy, and therapeutic use is largely ineffective. Most applications are by spray treatments in orchards. Monitoring and surveillance for drug resistance are not routinely done. In the United States, data on use of antimicrobials for treatment of bacterial diseases of plants are limited to streptomycin and oxytetracycline. Resistance to streptomycin has become widespread among bacterial phytopathogens; no resistance among these bacteria has yet been reported for oxytetracycline. No human health effects have been documented since inception of use of antimicrobials in plants in the 1950s. Transfer of antimicrobial resistance from marker genes in transgenic plants to bacteria has not been documented under natural conditions in field-grown plants. However, antimicrobial-resistance genes are being eliminated from use as marker genes because of concerns about possible transfer from plant genomes back to bacteria, with further horizontal transfer to the bacteria in the environment, or from plant genomes to animals by plant consumption. No new antimicrobials are expected to be used in plant agriculture because of high costs of development, regulatory constraints, and environmental and human health concerns. Alternatives to antimicrobials, such as biocontrol agents, transgenic plants, and novel chemicals, are being developed and marketed, although their efficacy remains to be determined.200211988880