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.     

Multiple Selection Criteria for Probiotic Strains with High Potential for Obesity Management

Since alterations of the gut microbiota have been shown to play a major role in obesity, probiotics have attracted attention. Our aim was to identify probiotic candidates for the management of obesity using a combination of in vitro and in vivo approaches. We evaluated in vitro the ability of 23 strains to limit lipid accumulation in adipocytes and to enhance the secretion of satiety-promoting gut peptide in enteroendocrine cells. Following the in vitro screening, selected strains were further investigated in vivo, single, or as mixtures, using a murine model of diet-induced obesity. Strain Bifidobacterium longum PI10 administrated alone and the mixture of B. animalis subsp. lactis LA804 and Lactobacillus gasseri LA806 limited body weight gain and reduced obesity-associated metabolic dysfunction and inflammation. These protective effects were associated with changes in the hypothalamic gene expression of leptin and leptin receptor as well as with changes in the composition of gut microbiota and the profile of bile acids. This study provides crucial clues to identify new potential probiotics as effective therapeutic approaches in the management of obesity, while also providing some insights into their mechanisms of action.     

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.     

Fermented milks, probiotic cultures, and colon cancer

Colorectal cancer (CRC) is a major cause of death from cancer in the Western world. Approximately 70% of CRC is associated with environmental factors, probably mainly the diet. There is interest in the potential protective role of fermented milks containing probiotic cultures against CRC. This article analyzes the existing data from human, animal, and in vitro studies that explore whether consumption of milks fermented with probiotic cultures could play a role in colon cancer risk reduction. Cohort studies have failed to detect significant effects, but most case-control studies favor a protective role of fermented milks against colon cancer. Interventional studies have shown a shift of intermediate markers of CRC risk in human subjects from a high- to low-risk pattern after ingestion of fermented milks or probiotics. Animal studies consistently show a reduction in chemically induced colorectal tumor incidence and aberrant crypt formation accompanying probiotic administration. In vitro studies also provide evidence of protection, and permit a better understanding of active compounds involved, and of the mechanisms underlying their anticarcinogenic effects. Probiotics may beneficially modulate several major intestinal functions: detoxification, colonic fermentation, transit, and immune status, which may accompany the development of colon cancer. Although the evidence is not conclusive and much further research is required, the data reviewed constitute a promising body of evidence supporting the protective role of milks fermented with probiotic cultures in colon cancer risk reduction.     

Gut Microbiota Modulation in the Context of Immune-Related Aspects of Lactobacillus spp. and Bifidobacterium spp. in Gastrointestinal Cancers

Accumulating evidence has revealed the critical roles of commensal microbes in cancer progression and recently several investigators have evaluated the therapeutic effectiveness of targeting the microbiota. This gut microbiota-related approach is especially attractive in the treatment of gastrointestinal cancers. Probiotics supplementation is a microbiota-targeted strategy that appears to improve treatment efficacy; Lactobacillus spp. and Bifidobacterium spp. are among the most commonly used probiotic agents. These bacteria seem to exert immunomodulatory effects, impacting on the immune system both locally and systemically. The gut microbiota are able to affect the efficiency of immunotherapy, mainly acting as inhibitors at immune checkpoints. The effects of immunotherapy may be modulated using traditional probiotic strains and/or next generation probiotics, such as Akkermansia municiphila. It is possible that probiotics might enhance the efficiency of immunotherapy based on PD-1/PD-L1 and CTLA-4 but more data are needed to confirm this speculation. Indeed, although there is experimental evidence for the efficacy of several strains, the health-promoting effects of numerous probiotics have not been demonstrated in human patients and furthermore the potential risks of these products, particularly in oncologic patients, are rarely mentioned.     

Role of Probiotics in Modulating Human Gut Microbiota Populations and Activities in Patients with Colorectal Cancer—A Systematic Review of Clinical Trials

Background: Growing attention has been given to the role of nutrition and alterations of microbial diversity of the gut microbiota in colorectal cancer (CRC) pathogenesis. It has been suggested that probiotics and synbiotics modulate enteric microbiota and therefore may be used as an intervention to reduce the risk of CRC. The aim of this study was to evaluate the influence of probiotics/synbiotics administration on gut microbiota in patients with CRC. Methods: PubMed, Scopus, and Web of Science were searched between December 2020 and January 2021. Randomized controlled trials (RCTs) recruiting adults with CRC, who have taken probiotics/synbiotics for at least 6 days were included. Changes in gut microbiota and selected biochemical and inflammatory parameters (i.e., hsCRP, IL-2, hemoglobin) were retrieved. Results: The search resulted in 198 original research articles and a final 6 were selected as being eligible, including 457 subjects. The median age of patients was 65.4 years old and they were characterized by the median BMI value: 23.8 kg/m². The literature search revealed that probiotic/synbiotic administration improved enteric microbiota by increasing the abundance of beneficial bacteria such as Lactobacillus, Eubacterium, Peptostreptococcus, Bacillus and Bifidobacterium, and decreased the abundance of potentially harmful bacteria such as Fusobacterium, Porhyromonas, Pseudomonas and Enterococcus. Additionally, probiotic/synbiotic intervention improved release of antimicrobials, intestinal permeability, tight junction function in CRC patients. Conclusions: The use of probiotics/synbiotics positively modulates enteric microbiota, improves postoperative outcomes, gut barrier function and reduces inflammatory parameters in patients suffering from CRC.     

New insights into the impact of the intestinal microbiota on health and disease: a symposium report

The present report summarises key insights from a recent symposium focusing on the impact of the intestinal microbiota on health and disease. A more appropriate definition of health was proposed since health maintenance is a dynamic process better assessed in terms of ability to adapt to stress and maintain physiological homeostasis. Biomarkers specifically for health are needed; use of challenge models and subjects with suboptimal health or specific disease risk were advised. The complexity of interactions between external factors, the intestinal epithelium, intestinal microbiota, the immune system and health was exemplified by describing the effects of antibiotics, the Western diet and non-digestible carbohydrates on the microbiota. The association of certain bacteria with different states of health or disease was acknowledged but also that is not always clear whether this is a cause or effect. Recent identification of three robust faecal metagenome clusters may advance this understanding. It was speculated that knowledge of the intestinal microbiota profile may eventually help in the diagnosis of health risks and choice of therapy. It was agreed that beneficial manipulation of the commensal microbiota can improve health outcome. For this purpose, three areas were reviewed. Firstly, research into probiotics as vaccine adjuvants was considered useful for substantiation of immune function claims. Secondly, positive results with certain probiotics and synbiotics for colorectal cancer are emerging, mostly from in vitro and animal studies. Finally, studies in endurance athletes have shown strain-specific probiotic benefit in terms of maintenance of immune function and, for certain strains, reduction of episodes of respiratory and/or gastrointestinal tract infections.     

Intestinal colonisation, microbiota and future probiotics?

The human intestine is colonized by a large number of microorganisms, collectively termed microbiota, which support a variety of physiological functions. As the major part of the microbiota has not yet been cultured, molecular methods are required to determine microbial composition and the impact of specific dietary components including probiotics. Probiotics are viable microbial food supplements, which have a beneficial impact on human health. Health-promoting properties have been demonstrated for specific probiotic products. The most significant demonstrations for probiotic efficacy include prevention and treatment of antibiotic associated diarrhea, rotavirus diarrhea and allergy prevention. Lactobacillus rhamnosus GG (=ATCC 53103) and Bifidobacterium lactis Bb12 are the among the best-characterized and most studied probiotic strains with demonstrated impact on human health. New complex targets for probiotics include irritable bowel syndrome and Helicobacter pylori infection. For future probiotics the most important target is a demonstrated clinical benefit supported by knowledge on the mechanistic actions in the microbiota of the target population. Molecular and genomics-based knowledge of the composition and functions of the microbiota, as well as deviations from the balanced microbiota, will advance the selection of new and specific probiotics. Potential combinations of specific probiotics may prove to be the next step to reduce the risk on intestinal diseases and reconstruct specific microbial deviations.     

Probiotics that modify disease risk

Probiotics are defined as live bacterial preparations with clinically documented health effects in humans. Probiotics have specific properties and targets in the human intestinal tract and intestinal microbiota. Each probiotic strain, independent of its genus and species is unique and, thus, the properties and the human health effects of each strain have to be assessed in a case-by-case manner. Understanding the mechanisms by which probiotics influence the normal intestinal microbiota and counteract aberrancies in microbiota would facilitate the use of probiotics for both dietary management and reduction in risk of specific diseases. Development of intestinal microbiota is an important factor affecting the health of the newborn. Recent studies suggest that specific bacterial components, especially the bifidobacteria, have a key impact on development of a healthy balanced infant microbiota. The composition of infant and child intestinal microbiota may become aberrant and thus influence the development of diarrheal, inflammatory, and allergic diseases. Based on this understanding, positive health effects of probiotics have been reported in the management of diarrheal, inflammatory, and allergic diseases in infants. Most recently, a reduction in risk of atopic diseases followed early administration of specific probiotics.     

Probiotics and mucosal barrier in children

PURPOSE OF REVIEW: Colonization by the microbiota plays an important role in intestinal tract maturation of newborn. Once installed, indigenous microbiota maintains this modulation and also protects against infectious aggression. Due to these abilities, gut microbiota can be considered a 'microbial organ' that contributes to health of human host. Factors can affect microbiota colonization as well as its maintenance and ingestion of probiotics is a promissory way to counteract these perturbations. This review discusses recent papers dealing with the use of probiotics and their effects on intestinal barrier in children. RECENT FINDINGS: Data obtained from experiments in animal models or cell cultures as well as from clinical trials suggest that probiotics may prevent infectious and inflammatory diseases in which reduction of mucosal barrier functions is involved. SUMMARY: Recent results suggest that probiotics control maturation and maintenance of the intestinal barrier in children. However, human data are limited and more biological and well controlled clinical trials must be carried out for a more precise understanding of the mechanisms underlying the probiotic action and the balance of the complex gastrointestinal ecosystem with which probiotics are expected to interact.     

The role of probiotics in gastrointestinal surgery

The intestinal microbiota, which is a complex and dynamic population of different bacterial species, represents an important contribution to the health of the host. This microbiota plays a key role by promoting the integrity of the epithelial barrier and the development of mucosal immunity. However, under some stressful situations, such as after gastrointestinal surgery, infectious complications may originate from the intestinal microbiota of the patient. This phenomenon is known as the gut origin of sepsis hypothesis. However, the supply of probiotics has beneficial effects under similar conditions despite some controversial results. Therefore, it is important to carefully assess the efficacy of probiotics in the prevention and treatment of complications in surgical patients and to evaluate the safety of its use. This review provides an overview of the proposed mechanisms of probiotic action and the significant progress in this field, mainly concerning gastrointestinal surgery.     

The Use of Probiotics for Management and Improvement of Reproductive Eubiosis and Function

Reproductive tract dysbiosis, due to the action of pathogens and/or unhealthy lifestyle, has been related to many reproductive diseases and disorders in mammalian species. Classically, such a problem has been confronted by the administration of antibiotics. Despite their effectiveness for controlling disease, treatments with antibiotics may negatively affect the fertility of males and females and, mainly, may induce antibiotic resistance. Accordingly, safer alternatives for maintaining reproductive system eubiosis, such as probiotics, are required. The present review summarizes the current knowledge on the biodiversity of the microbiota at the reproductive tract, possible changes in the case of dysbiosis, and their relationships with adequate reproductive health and functioning in both females and males. Afterwards, mechanisms of action and benefits of different probiotics are weighed since the biological activities of probiotics may provide a promising alternative to antibiotics for maintaining and restoring reproductive eubiosis and function. However, at present, it is still necessary for further research to focus on: (a) identifying mechanisms by which probiotics can affect reproductive processes; (b) the safety of probiotics to the host, specifically when consumed during sensitive reproductive windows such as pregnancy; and (c) the hazards instructions and regulatory rules required for marketing these biological-based therapies with sufficient safety. Thus, in this review, to draw a comprehensive overview with a relatively low number of clinical studies in this field, we showed the findings of studies performed either on human or animal models. This review strategy may help provide concrete facts on the eligible probiotic strains, probiotics colonization and transfer route, and prophylactic and/or therapeutic effects of different probiotic strains.     

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.     

Potential Role of Probiotics in Ameliorating Psoriasis by Modulating Gut Microbiota in Imiquimod-Induced Psoriasis-Like Mice

Psoriasis is an immune-mediated systemic disease that may be treated with probiotics. In this study, probiotic strains that could or could not decrease interleukin (IL)-17 levels were applied to imiquimod (IMQ)-induced psoriasis-like mice via oral administration. Bifidobacterium adolescentis CCFM667, B. breve CCFM1078, Lacticaseibacillus paracasei CCFM1074, and Limosilactobacillus reuteri CCFM1132 ameliorated psoriasis-like pathological characteristics and suppressed the release of IL-23/T helper cell 17 (Th17) axis-related inflammatory cytokines, whereas B. animalis CCFM1148, L. paracasei CCFM1147, and L. reuteri CCFM1040 neither alleviated the pathological characteristics nor reduced the levels of inflammatory cytokines. All effective strains increased the contents of short-chain fatty acids, which were negatively correlated with the levels of inflammatory cytokines. By performing 16S rRNA gene sequencing, the diversity of gut microbiota in psoriasis-like mice was found to decrease, but all effective strains made some specific changes to the composition of gut microbiota compared to the ineffective strains. Furthermore, except for B. breve CCFM1078, all other effective strains decreased the abundance of the family Rikenellaceae, which was positively correlated with psoriasis-like pathological characteristics and was negatively correlated with propionate levels. These findings demonstrated effects of strain-specificity, and how probiotics ameliorated psoriasis and provide new possibilities for the treatment of psoriasis.     

Rôles des manipulations du microbiote intestinal en réanimation

The intestinal microbiota displays dramatic changes in the ICU patient, with a loss of the entire beneficial lactic bacterial flora. In situations of hyperinflammation followed by immune paresis that are due to the acute disease but also to chronic diseases and drugs used, it is crucial to reestablish inflammatory and immune homeostasis, and microbiota manipulations with probiotics or synbiotics is an instrument of choice. It is not recommended to give any ICU patient any probiotic or synbiotic, for fear of inefficacy or even increased mortality. However, there is strong evidence in elective surgery, polytrauma and acute pancreatitis for well-defined formulations of bacterial strains and fibers. The inflammatory response is immediate and therefore administration of probiotics or synbiotics in these situations must also be immediate.     

Probiotic-enriched milk and dairy products increase gut microbiota diversity: a comparative study

Targeting gut microbiota with probiotics has emerged as a promising nutritional approach for the prevention of obesity and metabolic syndrome. Cultured dairy products can be effectively employed for the delivery of probiotics to the gut as well as for the support of growth and survival of probiotic bacteria. The purpose of this study was to characterize the effects of probiotic-enriched pasteurized milk and dairy products (Greek-style yogurt and cottage cheese) of different origins (cow, goat, and camel) on taxonomic composition of the mouse gut microbiota. We hypothesized that cultured dairy products can be an effective vector for the delivery of probiotics to the gut because of its nutritional value, acidic nature, and long shelf-life. Mice were fed a standard low fat, plant polysaccharide-rich (LF/PP) diet supplemented with the probiotic-enriched milk and dairy products for 5 weeks. Next generation sequencing of DNA from mouse fecal samples was used to characterize the bacterial relative abundance. Mice fed a diet supplemented with camel milk demonstrated characteristic changes in the gut microbiota, which included an increase in relative abundance of order Clostridiales and genus Anaerostipes. Mice fed a diet supplemented with the probiotic-enriched cow cheese exhibited an increase in the relative abundance of order Clostridiales, family Ruminococcaceae, and family Lachnospiraceae. The results obtained and their bioinformatics analysis support the conclusion that camel milk and the probiotic cow cheese induce changes in the mouse gut microbiota, which can be characterized as potentially beneficial to health compared to the changes associated with a standard diet. These findings imply that probiotic-enriched milk and dairy products can be highly effective for the delivery and support of probiotic bacteria of the gut.     

Probiotics Improve Gastrointestinal Function and Life Quality in Pregnancy

We studied whether probiotics were beneficial for hormonal change-associated dysbiosis, which may influence the enteric nervous system and GI function during early pregnancy. The study was 16 days consisting of two cycles of six daily probiotics mainly Lactobacillus and 2 days without probiotics. Daily surveys were conducted to monitor GI function and life quality. A subset of the participants who contributed fecal specimens was used for microbiota metagenomic sequencing, metabolomics, and quantification of bacterial genes to understand potential underlying mechanisms. Statistical analyses were done by generalized linear mixed-effects models. Thirty-two obstetric patients and 535 daily observations were included. The data revealed that probiotic supplementation significantly reduced the severity of nausea, vomiting, constipation, and improved life quality. Moreover, a low copy number of fecal bsh (bile salt hydrolase), which generates free bile acids, was associated with high vomiting scores and probiotic intake increased fecal bsh. In exploratory analysis without adjusting for multiplicity, a low fecal α-tocopherol, as well as a high abundance of Akkemansia muciniphila, was associated with high vomiting scores and times, respectively. The potential implications of these biomarkers in pregnancy and GI function are discussed. Probiotics likely produce free bile acids to facilitate intestinal mobility and metabolism.     

Postbiotic Supplementation for Children and Newborn’s Health

It is now well known how the microbiota can positively or negatively influence humans health, depending on its composition. The microbiota’s countless beneficial effects have allowed it to be defined as a genuine symbiont for our species. In an attempt to positively influence the microbiota, research has focused on probiotics and prebiotics. Probiotics are viable beneficial bacteria of various strains. Prebiotics are specific substances able to favor the development of advantageous bacteria strains. Postbiotics are a new category of compounds capable of affecting the microbiota. According to the different definitions, postbiotics include both nonviable bacteria and substances deriving from bacterial metabolism. Postbiotics are particularly promising in pediatric settings, as they offer some advantages over probiotics, including the absence of the risk of intestinal translocation or worsening of local inflammation. For these reasons, their use in fragile population categories such as newborns, and even more prematures, seems to be the best solution for improving microbiota’s health in this population. This narrative review aims to collect the research conducted so far on postbiotics’ potential in the first stages of life.     

Probiotics in Pediatrics. A Review and Practical Guide

The potential benefit of the administration of probiotics in children has been studied in many settings globally. Probiotics products contain viable micro-organisms that confer a health benefit on the host. Beneficial effects of selected probiotic strains for the management or prevention of selected pediatric conditions have been demonstrated. The purpose of this paper is to provide an overview of current available evidence on the efficacy of specific probiotics in selected conditions to guide pediatricians in decision-making on the therapeutic or prophylactic use of probiotic strains in children. Evidence to support the use of certain probiotics in selected pediatric conditions is often available. In addition, the administration of probiotics is associated with a low risk of adverse events and is generally well tolerated. The best documented efficacy of certain probiotics is for treatment of infectious gastroenteritis, and prevention of antibiotic-associated, Clostridioides difficile-associated and nosocomial diarrhea. Unfortunately, due to study heterogeneity and in some cases high risk of bias in published studies, a broad consensus is lacking for specific probiotic strains, doses and treatment regimens for some pediatric indications. The current available evidence thus limits the systematic administration of probiotics. The most recent meta-analyses and reviews highlight the need for more well-designed, properly powered, strain-specific and dedicated-dose response studies.