The use of probiotics in gastrointestinal diseases

Probiotics represent a potential important therapy resource. Nevertheless, no clear-cut evidence about their use has yet been established. In fact, numerous studies exist on the application of probiotics in gastrointestinal disease but results are often controversial or produced from an inadequate study design. The aim of this review is to analyze the main experimental data regarding the use of probiotics. In particular, analyses have identified what probiotic strains could be used in acute diseases such as diarrhea and in chronic ones like inflammatory bowel diseases, irritable bowel syndrome, dysbiosis, Helicobacter pylori colonisation, and necrotizing enterocolitis. Finally, this review also provides an observation about the actual need of efficient research on the safety of products containing probiotics, verifying the effects of probiotic therapy at short, medium, and long term. This information is very important and could ensure a safer and more conscious use of such therapeutic agents.     

Probiotics and inflammatory bowel disease: from fads and fantasy to facts and future

Probiotic therapy is attracting the renewed interest of clinicians and basic investigators from a variety of traditional research disciplines. While the theoretical rationale for modifying the commensal flora of the gastrointestinal tract in specific circumstances appears sound and requires scientific pursuit, the field of probiotics has been clouded by exaggerated claims from some quarters. In general, many of the claims for therapeutic efficacy have not been well substantiated, but the field is now poised for evaluation within the realm of evidence-based medicine. Alterations in commensal bacterial flora within the gastrointestinal tract are associated with susceptibility to pathogens such as Clostridium difficile and there is persuasive evidence that the normal flora may participate in the pathogenesis of inflammatory bowel disease and other chronic diseases in genetically susceptible individuals. This has prompted various strategies to fortify or otherwise modify the enteric flora by dietary supplements containing probiotic formulations. Detailed comparisons of probiotic performance amongst different bacterial strains have not been performed in vivo in man or under clinical trial conditions, and the level of scientific characterisation of individual organisms has been variable. In addition, it cannot be assumed that the same probiotic is equally suitable for all individuals. Moreover, the heterogeneity of clinical disorders such as Crohn's disease and ulcerative colitis implies that strain-specific properties may be required for subset-specific categories of patients. While cocktails of probiotics offer convenience, therapeutic progress may require clarification of the mechanism of probiotic action and may be delayed until individual bacterial components have been rigorously studied. More importantly, the full potential of therapeutic manipulation of the enteric flora with probiotics or other strategies may not be optimally realised until the composition and metabolic activities of the normal flora are better understood.     

Use of probiotics as prophylaxis for postoperative infections

Postoperative bacterial infections are common despite prophylactic administration of antibiotics. The wide-spread use of antibiotics in patients has contributed to the emergence of multiresistant bacteria. A restricted use of antibiotics must be followed in most clinical situations. In surgical patients there are several reasons for an altered microbial flora in the gut in combination with an altered barrier function leading to an enhanced inflammatory response to surgery. Several experimental and clinical studies have shown that probiotics (mainly lactobacilli) may reduce the number of potentially pathogenia bacteria (PPM) and restore a deranged barrier function. It is therefore of interest to test if these abilities of probiotics can be utilized in preoperative prophylaxis. These factors may be corrected by perioperative administration of probiotics in addition to antibiotics. Fourteen randomized clinical trials have been presented in which the effect of such regimens has been tested. It seems that in patients undergoing liver transplantation or elective surgery in the upper gastrointestinal tract prophylactic administration of different probiotic strains in combination with different fibers results in a three-fold reduction in postoperative infections. In parallel there seems to be a reduction in postoperative inflammation, although that has not been studied in a systematic way. The use of similar concepts in colorectal surgery has not been successful in reducing postoperative infections. Reasons for this difference are not obvious. It may be that higher doses of probiotics with longer duration are needed to influence microbiota in the lower gastrointestinal tract or that immune function in colorectal patients may not be as important as in transplantation or surgery in the upper gastrointestinal tract. The favorable results for the use of prophylactic probiotics in some settings warrant further controlled studies to elucidate potential mechanisms, impact on gut microbiota and influence on clinical management. The use of probiotics must be better delineated in relation to type of bacteria, dose and length of administration.     

Safety of probiotics

New species and more specific strains of probiotic bacteria are constantly being sought for novel probiotic products. Prior to the incorporation of novel strains into food or therapeutic products a careful evaluation of their efficacy is required and an assessment made as to whether they share the safety status of traditional food organisms. Food organisms intrinsic to the production of traditional foods have been arbitrarily classified as safe in the absence of scientific criteria. Evidence for the safety and efficacy of probiotics has until recently been largely anecdotal or based on relatively little, and often poorly designed research. The demonstration of efficacy in probiotics offers vast opportunities for the development of human and veterinary products. The introduction of a new probiotic culture demands that it be at least as safe as its conventional counterparts. Many bacteria are being tested to find a putative probiotic, yielding conflicting data, sometimes for the same organism. Comparisons between studies and organisms cannot be readily made because of non-standardized dosing procedures. Information is not readily available on the equivalence of formulations for different probiotic preparations. There is vigorous debate on what constitutes appropriate safety testing for novel probiotic strains proposed for human consumption. Conventional toxicology and safety evaluation is of limited value in assessing the safety of probiotics. The addition of novel bacterial strains to foods and therapeutic products requires reconsideration of the procedures for safety assessment. This paper provides an overview of these issues.     

Probiotics: From Isolation to Application

Probiotics have become highly recognized as supplements for humans and animals because of their beneficial effects on health and well-being. The present review aims to provide an overview of different steps through which microbial strains become applicable probiotics in food and/or feed industries. Isolation of potential probiotic strains is the first step. Lactic acid bacteria are the most frequently used microorganisms as probiotics, which can be isolated from human, animal, plant, and environment. The next steps are identification of the isolates and characterization of them based on the main selection criteria for any potential probiotic microorganism, including resistance to gastric acidity and bile salt, adherence to mucus and/or intestinal epithelial cells and cell lines, and antimicrobial and antagonism activity against potentially pathogenic microbes. There are additional probiotic properties that may be considered for selection of probiotic strains with specific effects, such as cholesterol reduction ability, antioxidant activity, or cytotoxic effect against cancer cells. However, a potential probiotic does not need to fulfill all such selection criteria. As the last step, safety status of probiotics for humans is verified by taxonomy clarification, in vitro and in vivo tests, human trials, and genome sequencing.     

Probiotics for inflammatory bowel diseases: a promising adjuvant treatment

Inflammatory bowel diseases (IBD) encompass ulcerative colitis (UC), Crohn’s disease (CD) and indeterminate colitis (IC), characterising chronic inflammation in the gastrointestinal tract, associated with changes in the immune system and in the intestinal microbiota. Thus, probiotics may offer an alternative or adjuvant approach to conventional therapy. The present review aims to summarise the mechanisms of action of probiotics in IBD and their therapeutic effects. Most of the studies suggest that probiotics are effective in the treatment of UC, especially when several strains are concomitantly administered. Species of Lactobacillus and Bifidobacterium genres are the most commonly used, and some studies even indicate that it is possible to replace medical therapy with probiotic supplementation. Regarding CD, the results of clinical trials are controversial and do not support the use of probiotics in this disease. In conclusion, probiotic supplementation is a promising adjuvant treatment in UC, but not in CD.     

Probiotics Administration in Cystic Fibrosis: What Is the Evidence?

In the last 20 years, gut microbiota in patients with cystic fibrosis (CF) has become an object of interest. It was shown that these patients had gut dysbiosis and this could explain not only the intestinal manifestations of the disease but also part of those involving the respiratory tract. The acquisition of previously unknown information about the importance of some bacteria, i.e., those partially or totally disappeared in the gut of CF patients, in the regulation of the activity and function of the gut and the lung was the base to suggest the use of probiotics in CF patients. The main aim of this paper is to discuss the biological basis for probiotic administration to CF patients and which results could be expected. Literature analysis showed that CF intestinal dysbiosis depends on the same genetic mutations that condition the clinical picture of the diseases and is aggravated by a series of therapeutic interventions, such as dietary modifications, the use of antibiotics, and the administration of antacids. All this translates into a significant worsening of the structure and function of organs, including the lung and intestine, already deeply penalized by the genetic alterations of CF. Probiotics can intervene on dysbiosis, reducing the negative effects derived from it. However, the available data cannot be considered sufficient to indicate that these bacteria are essential elements of CF therapy. Further studies that take into account the still unsolved aspects on how to use probiotics are absolutely necessary.     

Review of the mechanisms of probiotic actions in the prevention of colorectal cancer

The purpose of this review is to discuss the potential mechanisms of probiotics action in colorectal cancer prevention. In this regard, the composition of the intestinal microbiota is considered as an important risk factor in the development of colorectal cancer, and probiotics are able to positively modulate the composition of this microbiota. Studies have shown that the regular consumption of probiotics could prevent the development of colorectal cancer. In this respect, in vitro and experimental studies suggest some potential mechanisms responsible for this anticarcinogenic action. The mechanisms include modification of the intestinal microbiota composition, changes in metabolic activity of the microbiota, binding and degradation of carcinogenic compounds present in the intestinal lumen, production of compounds with anticarcinogenic activity, immunomodulation, improvement of the intestinal barrier, changes in host physiology, inhibition of cell proliferation, and induction of apoptosis in cancer cells. In contrast, very few reports demonstrate adverse effects of probiotic oral supplementation. In light of the present evidence, more specific studies are needed on probiotic bacteria, especially regarding the identification of the bacterial strains with greater anticarcinogenic potential; the verification of the viability of these strains after passing through the gastrointestinal tract; the investigation of potential adverse effects in immunocompromised individuals; and finally establishing the dosage and frequency of use.     

Probiotics,gut microbiota and health

The human gut is a huge complex ecosystem where microbiota, nutrients, and host cells interact extensively, a process crucial for the gut homeostasis and host development with a real partnership. The various bacterial communities that make up the gut microbiota have many functions including metabolic, barrier effect, and trophic functions. Hence, any dysbiosis could have negative consequences in terms of health and many diseases have been associated to impairment of the gut microbiota. These close relationships between gut microbiota, health, and disease, have led to great interest in using probiotics (i.e. live micro-organisms), or prebiotics (i.e. non-digestible substrates) to positively modulate the gut microbiota to prevent or treat some diseases. This review focuses on probiotics, their mechanisms of action, safety, and major health benefits. Health benefits remain to be proven in some indications, and further studies on the best strain(s), dose, and algorithm of administration to be used are needed. Nevertheless, probiotic administration seems to have a great potential in terms of health that justifies more research.     

Probiotics and health: a review of the evidence

Probiotics are live microorganisms – mainly bacteria – which when administered in adequate amounts confer a health benefit on the host. There is rising interest in this area, but reports in the media are often conflicting. The aim of this review is to consider the current evidence on the effects of probiotics on health, focusing on gut‐related health issues and the immune system, with the objective to provide a clearer picture of whether and how probiotics can be beneficial for health. The outcomes of this review are based on more than 100 original studies, meta‐analyses and systematic reviews. A variety of different strains have been used in studies on probiotics, and it is important to remember that the effectiveness of probiotics is strain‐specific, which means that each single probiotic strain has to be tested to assess its potential health benefits. Overall, despite the diversity of strains used in the studies included in this review, there is evidence that probiotics have the potential to be beneficial for our health. Studies in patients with inflammatory bowel disease show probiotic strains to be able to decrease the recurrence of ulcerative colitis and occurrence and recurrence of pouchitis, however, current evidence suggests that probiotics are ineffective in treating patients with Crohn's disease. Patients with irritable bowel syndrome show a reduction in symptoms when treated with selected probiotic strains, but high placebo effects have been reported as well. The evidence of the efficacy of probiotics in patients suffering from constipation is limited, but the evidence seems promising for some strains to bring relief to patients suffering from constipation. There is good evidence that a number of probiotic strains are effective in preventing antibiotic‐associated diarrhoea. The most commonly studied strains are Lactobacillus rhamnosus GG (LGG) and Saccharomyces boulardii, but other strains and mixtures of strains seem to be effective as well. There is also promising evidence of a preventive effect of probiotics in Clostridium difficile‐associated diarrhoea, although some studies have been too small to obtain statistically significant findings. The effect of probiotics in acute diarrhoea, particularly in children, is well studied. Selected probiotic strains seem to be effective in reducing the duration of acute diarrhoea. LGG and S. boulardii are again the most commonly used strains and a number of studies have shown them to be effective, although one meta‐analysis showed that the effect of LGG was only significant in children in Western countries, not in children in developing countries, which may be due to different causes of diarrhoea in these regions. Studies investigating the preventive effect of probiotics in the context of common cold and flu infections show that the studied strains failed to lower the incidence of episodes but that they have the potential to decrease the duration of episodes, which suggests that the immune system may be more efficient in fighting off common cold and flu infections after consuming these strains. The evidence so far does not suggest that probiotics are effective in preventing or treating allergies or in treating eczema. However, some probiotic strains seem to lower the risk of developing eczema if taken by pregnant women and their infants in early life.     

The Potential Role of Probiotics in Cancer Prevention and Treatment

The human gut microbiota has a significant effect on many aspects of human physiology such as metabolism, nutrient absorption, and immune function. Imbalance of the microbiota has been implicated in many disorders including inflammatory bowel disease, obesity, asthma, psychiatric illnesses, and cancers. As a kind of functional foods, probiotics have been shown to play a protective role against cancer development in animal models. Clinical application of probiotics indicated that some probiotic strains could diminish the incidence of postoperative inflammation in cancer patients. Chemotherapy or radiotherapy-related diarrhea was relieved in patients who were administered oral probiotics. The present review summarizes the up-to-date studies on probiotic effects and the underlying mechanisms related to cancer. At present, it is commonly accepted that most commercial probiotic products are generally safe and can improve the health of the host. By modulating intestinal microbiota and immune response, some strains of probiotics can be used as an adjuvant for cancer prevention or/and treatment.     

Probiotics as modulators of the gut flora

Probiotic ingestion can be recommended as a preventative approach to maintaining the balance of the intestinal microflora and thereby enhance 'well-being'. Research into the use of probiotic intervention in specific illnesses and disorders has identified certain patient populations that may benefit from the approach. Undoubtedly, probiotics will vary in their efficacy and it may not be the case that the same results occur with all species. Those that prove most efficient will likely be strains that are robust enough to survive the harsh physico-chemical conditions present in the gastrointestinal tract. This includes gastric acid, bile secretions and competition with the resident microflora. A survey of the literature indicates positive results in over fifty human trials, with prevention/treatment of infections the most frequently reported output. In theory, increased levels of probiotics may induce a 'barrier' influence against common pathogens. Mechanisms of effect are likely to include the excretion of acids (lactate, acetate), competition for nutrients and gut receptor sites, immunomodulation and the formation of specific antimicrobial agents. As such, persons susceptible to diarrhoeal infections may benefit greatly from probiotic intake. On a more chronic basis, it has been suggested that some probiotics can help maintain remission in the inflammatory conditions, ulcerative colitis and pouchitis. They have also been suggested to repress enzymes responsible for genotoxin formation. Moreover, studies have suggested that probiotics are as effective as anti-spasmodic drugs in the alleviation of irritable bowel syndrome. The approach of modulating the gut flora for improved health has much relevance for the management of those with acute and chronic gut disorders. Other target groups could include those susceptible to nosocomial infections, as well as the elderly, who have an altered microflora, with a decreased number of beneficial microbial species. For the future, it is imperative that mechanistic interactions involved in probiotic supplementation be identified. Moreover, the survival issues associated with their establishment in the competitive gut ecosystem should be addressed. Here, the use of prebiotics in association with useful probiotics may be a worthwhile approach. A prebiotic is a dietary carbohydrate selectively metabolised by probiotics. Combinations of probiotics and prebiotics are known as synbiotics.     

What Do We Know about the Microbiome in Cystic Fibrosis? Is There a Role for Probiotics and Prebiotics?

Cystic fibrosis (CF) is a life-shortening genetic disorder that affects the cystic fibrosis transmembrane conductance regulator (CFTR) protein. In the gastrointestinal (GI) tract, CFTR dysfunction results in low intestinal pH, thick and inspissated mucus, a lack of endogenous pancreatic enzymes, and reduced motility. These mechanisms, combined with antibiotic therapies, drive GI inflammation and significant alteration of the GI microbiota (dysbiosis). Dysbiosis and inflammation are key factors in systemic inflammation and GI complications including malignancy. The following review examines the potential for probiotic and prebiotic therapies to provide clinical benefits through modulation of the microbiome. Evidence from randomised control trials suggest probiotics are likely to improve GI inflammation and reduce the incidence of CF pulmonary exacerbations. However, the highly variable, low-quality data is a barrier to the implementation of probiotics into routine CF care. Epidemiological studies and clinical trials support the potential of dietary fibre and prebiotic supplements to beneficially modulate the microbiome in gastrointestinal conditions. To date, limited evidence is available on their safety and efficacy in CF. Variable responses to probiotics and prebiotics highlight the need for personalised approaches that consider an individual’s underlying microbiota, diet, and existing medications against the backdrop of the complex nutritional needs in CF.     

Crosstalk between Gut and Brain in Alzheimer’s Disease: The Role of Gut Microbiota Modulation Strategies

The gut microbiota (GM) represents a diverse and dynamic population of microorganisms and about 100 trillion symbiotic microbial cells that dwell in the gastrointestinal tract. Studies suggest that the GM can influence the health of the host, and several factors can modify the GM composition, such as diet, drug intake, lifestyle, and geographical locations. Gut dysbiosis can affect brain immune homeostasis through the microbiota–gut–brain axis and can play a key role in the pathogenesis of neurodegenerative diseases, including dementia and Alzheimer’s disease (AD). The relationship between gut dysbiosis and AD is still elusive, but emerging evidence suggests that it can enhance the secretion of lipopolysaccharides and amyloids that may disturb intestinal permeability and the blood–brain barrier. In addition, it can promote the hallmarks of AD, such as oxidative stress, neuroinflammation, amyloid-beta formation, insulin resistance, and ultimately the causation of neural death. Poor dietary habits and aging, along with inflammatory responses due to dysbiosis, may contribute to the pathogenesis of AD. Thus, GM modulation through diet, probiotics, or fecal microbiota transplantation could represent potential therapeutics in AD. In this review, we discuss the role of GM dysbiosis in AD and potential therapeutic strategies to modulate GM in AD.     

Safety of probiotics: translocation and infection

The long history of safety has contributed to the acceptance of probiotics as a safe food adjunct. Consequently, many probiotic products and their applications have been granted GRAS (generally regarded as safe) status. However, this classification has been frequently generalized for all probiotic strains regardless of their application. Cases of probiotics from the genera Lactobacillus, Leuconostoc, Pediococcus, Enterococcus, and Bifidobacterium have been isolated from infection sites, leading to the postulation that these probiotics can translocate. Probiotic translocation is difficult to induce in healthy humans, and even if it does occur, detrimental effects are rare. Despite this, various reports have documented health-damaging effects of probiotic translocation in immunocompromised patients. Due to probiotics' high degree of safety and their morphological confusion with other pathogenic bacteria, they are often overlooked as contaminants and are least suspected as pathogens. However, the antibiotic resistance of some strains has increased the complexity of their eradication. Probiotic translocation and infection deserve further investigation and should become a facet of safety assessment so the negative effects of probiotics do not outweigh the benefits.     

Probiotics as functional food in the treatment of diarrhea

PURPOSE OF REVIEW: A disturbance in microbial balance of the gastrointestinal tract is often associated with diarrhea. Therefore, probiotics, as beneficial microorganisms for host health, have attracted clinical attention for their potential therapeutic application in the treatment of diarrhea. This review focuses on new research findings relevant to the effects of probiotics on diarrhea prevention and treatment and potential mechanisms of action for this alternative therapy for diarrhea. RECENT FINDINGS: Clinical trials suggest potential beneficial effects of probiotic therapy for preventing and treating antibiotic-associated diarrhea, acute diarrhea including rotavirus-induced diarrhea, traveler's diarrhea, and diarrhea-predominant irritable bowel syndrome. The most extensively studied probiotics for diarrhea are Lactobacillus, Bifidobacterium and Saccharomyces, with potential mechanisms of therapeutic action based on the protection of intestinal epithelial cell and barrier function, prevention of enterotoxin binding to intestinal epithelial cells, and regulation of intestinal microbial environment. SUMMARY: Growing evidence suggests that probiotics may serve as a functional food in the treatment of diarrhea. Remaining challenges include identifying mechanisms of action to provide the basis of more refined hypothesis-driven clinical trials. The correct combination and concentration of probiotics applied to the appropriate gastrointestinal disorders may improve the efficacy of this approach for diarrhea and other diseases.     

‘Someone should oversee it’: patient perspectives on the ethical issues arising with the regulation of probiotics

Background

Although many probiotic products are currently available in yogurt or pill form in the United States (US), there is uncertainty surrounding the structure of regulation of these products. As more therapeutic probiotics are developed, changes to existing regulatory process in the United States may be required to meet the needs of patients and users in the population.

Objective

This study examined how patients with chronic gastrointestinal (GI) diseases view the regulation of probiotics.

Design

We conducted a multi‐site qualitative study consisting of focus groups of patients with chronic gastrointestinal diseases at three tertiary hospitals: at [institutions removed for blinded review].

Results

We conducted 22 focus groups with 136 patients with major gastrointestinal (GI) diseases between March and August 2009. Participants were not familiar with the existing regulation of probiotic products but wanted assurances of accurate labelling of strain as well as safety. Participants raised concerns that regulation of probiotics might be accompanied by greater costs, reduced access and increased involvement of pharmaceutical companies. Although participants voiced significant doubt of government regulators, they felt that products containing genetically modified probiotic strains should have oversight comparable to that of pharmaceutical drugs.

Discussion and conclusion

If GI patient perspectives are indicative of public perceptions of therapeutic probiotics in the United States, consumers may expect more rigorous regulation in the future while simultaneously wanting low costs, easy access and low involvement of pharmaceutical companies. Manufacturers, translational scientists, clinicians and regulators should be sensitive to consumer attitudes when designing, testing and regulating new therapeutic probiotics.     

The influence of probiotics on vaccine responses – A systematic review

The immunomodulatory effects of probiotics may influence the response to vaccines. We systematically reviewed prospective randomised placebo-controlled studies in humans that have investigated the effect of probiotics on humoral vaccine responses.We found 26 studies, involving 3812 participants, investigating the effect of 40 different probiotic strains on the response to 17 different vaccines. A beneficial effect of probiotics was reported in about half of the studies. The evidence for a beneficial effect of probiotics on vaccine response was strongest for oral vaccinations and for parenteral influenza vaccination. However, there was substantial variation between studies in the choice of probiotic, strain, dose, viability, purity, and duration and timing of administration. The one study that investigated the effect of probiotic administration to mothers during pregnancy found lower vaccine responses in their infants.The studies in our review suggest that probiotics offer a relatively cheap intervention to improve vaccine efficacy and duration of protection. Future studies should focus on establishing optimal strains, doses and timing of administration in relation to vaccination.     

Probiotics and Their Effect on Surgical Wound Healing: A Systematic Review and New Insights into the Role of Nanotechnology

Skin tissue repair is of fundamental importance for maintaining homeostasis regulation, protection barrier, absorption, and excretion of skin tissue. Wound healing is a complicated process that can be impaired by infections and therefore have a significant economic and social impact. Simultaneously, the overuse of antibiotics has led to antimicrobial resistance and loss of their efficacy. Thus, the need for alternative antimicrobial agents is urgent. The newest approaches on wound dressings employ new therapeutic agents, such as probiotics. Probiotics alone or in tandem with nanotechnology-based techniques exhibit a broad range of benefits on surgical wounds. This systematic review aims to consider current knowledge of probiotic effects on animals and humans regarding surgical wound healing and provide new insights into the role of nanotechnology. The databases included were PubMed (MEDLINE), Scopus, and Cochrane Library (CENTRAL). Studies focused on burns, chronic wounds, and diabetic ulcers were excluded. The promising industry of probiotics demonstrates a significant upsurge as more and more healthy individuals rely their well-being on alternative medicine. Included probiotics illustrated positive results on wound re-epithelization, neovascularization, and wound healing. No adverse effects were noted.     

Regulatory oversight and safety of probiotic use

Depending on intended use of a probiotic (drug vs. dietary supplement), regulatory requirements differ greatly. For dietary supplements, premarketing demonstration of safety and efficacy and approval by the Food and Drug Administration are not required; only premarket notification is required. Saccharomyces boulardii is a probiotic regulated as a dietary supplement intended for use by the general healthy population, not as a drug to prevent, treat, or mitigate disease. However, since recent increases in incidence and severity of Clostridium difficile infection, probiotics have been used to treat recurrent and/or refractory disease in hospitalized patients. Saccharomyces fungemia secondary to use of the probiotic has been described for patients who are critically ill, are receiving nutrition enterally, or have a central venous catheter. Before use of a probiotic is considered for hospitalized patients, careful assessment of risk versus benefit must be made. To ensure patient safety, probiotics should be properly handled during administration.