Design of a multispecies probiotic mixture to prevent infectious complications in critically ill patients

BACKGROUND & AIMS: Although the potential for probiotics is investigated in an increasing variety of diseases, there is little or no consensus regarding the desired probiotic properties for a particular disease in question, nor about the final design of the probiotic. Specific strain selection procedures were undertaken to design a disease-specific multispecies probiotic. METHODS: From a strain collection of 69 different lactic acid bacteria a primary selection was made of 14 strains belonging to different species showing superior survival in a simulated gastrointestinal environment. Functional tests like antimicrobial activity against a range of clinical isolates and cytokine inducing capacity in cultured human peripheral blood mononuclear cells were used to further identify potential strains. RESULTS: Specific strains inhibited growth of clinical isolates whereas others superiorly induced the anti-inflammatory cytokine IL-10. Based on functional tests and general criteria regarding probiotic design and safety, a selection of the following six strains was made (Ecologic 641); Bifidobacterium bifidum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus salivarius and Lactococcus lactis. Combination of these strains resulted in a wider antimicrobial spectrum, superior induction of IL-10 and silencing of pro-inflammatory cytokines as compared to the individual components. CONCLUSIONS: Application of strict criteria during the design of a disease-specific probiotic prior to implementation in clinical trials may provide a rational basis for use of probiotics.     

Dietary intervention with the probiotics Lactobacillus acidophilus 145 and Bifidobacterium longum 913 modulates the potential of human faecal water to induce damage in HT29clone19A cells

Probiotics reduce the risk of colon cancer by inhibiting carcinogen-induced DNA damage in animals, but there are no analogous data in human subjects. To enhance knowledge of the effects of probiotics in human subjects, we have investigated the genotoxicity of faecal water after dietary intervention with standard yoghurt or with probiotic yoghurt, which included the strains Lactobacillus acidophilus 145 and Bifidobacterium longum 913. Faeces were collected from nine healthy volunteers after intervention with probiotic yoghurt or standard yoghurt. Faecal water was isolated and incubated with human colon tumour cells HT29clone19A. DNA strand breaks, oxidised DNA bases and damage after challenge with H2O2 were determined by micro-gel-electrophoresis. Faecal water was genotoxic in comparison with NaCl, but protected against H2O2-induced DNA strand breaks. The intervention with probiotic yoghurt significantly lowered faecal water genotoxicity compared with standard yoghurt. However, probiotic intervention also increased oxidative damage; this either reflected prooxidative activity or stimulation of endogenous defence systems. Altogether, the balance of effects favoured protection, since faecal water from the probiotic group reduced overall genetic damage. Thus, there was a reduction of strand break-inducing compounds in human faeces after dietary intervention with probiotic bacteria. This protection reflected results from previous studies in carcinogen-exposed animals where probiotics reduced DNA damage in colon cells.     

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.     

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.     

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.     

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.     

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.     

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.     

Nondairy Probiotic Products: Functional Foods That Require More Attention

The potential health benefits of probiotics have been illustrated by many studies. However, most functional foods containing probiotics are from dairy sources. This review provides an overview of potential strains and raw materials for nondairy probiotic products together with the role of its in vitro assessment. Probiotic-containing products from raw nondairy materials are known both in terms of quality and nutritional values. The sensory properties of raw plant-based materials are generally improved as a result of fermentation with probiotics. Increased market shares for plant-based probiotic products may also help to curb environmental challenges. The sustainability of this food results from reductions in land use, greenhouse gas emissions, and water use during production. Consuming nondairy probiotic food can be a personal step to contribute to climate change mitigation. Since some people cannot or do not want to eat dairy products, this creates a market gap in the supply of nutritious food. Therefore, the promotion and broader development of these foods are needed. Expanding our knowledge on how to best produce these functional foods and increasing our understanding of their in vivo behaviours are crucial. The latter may be efficiently achieved by utilizing available in vitro digestion systems that reliably recapitulate the in vivo situation without introducing any ethical concerns.     

Probiotics Lactobacillus rhamnosus GG,Lactobacillus acidophilus Suppresses DMH-Induced Procarcinogenic Fecal Enzymes and Preneoplastic Aberrant Crypt Foci in Early Colon Carcinogenesis in Sprague Dawley Rats

Diet makes an important contribution to colorectal cancer (CRC) risk implying risks for CRC are potentially reducible. Therefore, the probiotics have been suggested as the prophylactic measure in colon cancer. In this study, different probiotics were used to compare their protective potential against 1,2 dimethylhydrazine dihydrochloride (DMH)-induced chemical colon carcinogenesis in Sprague Dawley rats. Animals belonging to different probiotic groups were fed orally with 1 × 10⁹ lactobacilli daily for 1 week, and then a weekly injection of DMH was given intraperitoneally for 6 wks with daily administration of probiotic. Lactobacillus GG and L.acidophilus + DMH-treated animals had maximum percent reduction in ACF counts. A significant decrease (P < 0.05) in fecal nitroreductase activity was observed in L.casei + DMH and L.plantarum + DMH-treated rats whereas β-glucuronidase activity decreased in L.GG + DMH and L.acidophilus + DMH-treated rats. Animals treated with Bifidobacterium bifidum + DMH had significant decreased β-glucosidase activity. However, not much difference was observed in the colon morphology of animals belonging to various probiotic + DMH-treated rats compared with DMH-treated alone. The results indicated that probiotics, L.GG, and L.acidophilus can be used as the better prophylactic agents for experimental colon carcinogenesis.     

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.     

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.     

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.     

Comparative in vitro inhibition of urinary tract pathogens by single- and multi-strain probiotics

Purpose

Multi-species probiotic preparations have been suggested as having a wide spectrum of application, although few studies have compared their efficacy with that of individual component strains at equal concentrations. We therefore tested the ability of 4 single probiotics and 4 probiotic mixtures to inhibit the urinary tract pathogens Escherichia coli NCTC 9001 and Enterococcus faecalis NCTC 00775.

Methods

We used an agar spot test to test the ability of viable cells to inhibit pathogens, while a broth inhibition assay was used to assess inhibition by cell-free probiotic supernatants in both pH-neutralised and non-neutralised forms.

Results

In the agar spot test, all probiotic treatments showed inhibition, L. acidophilus was the most inhibitory single strain against E. faecalis, L. fermentum the most inhibitory against E. coli. A commercially available mixture of 14 strains (Bio-Kult^®) was the most effective mixture, against E. faecalis, the 3-lactobacillus mixture the most inhibitory against E. coli. Mixtures were not significantly more inhibitory than single strains. In the broth inhibition assays, all probiotic supernatants inhibited both pathogens when pH was not controlled, with only 2 treatments causing inhibition at a neutral pH.

Conclusions

Both viable cells of probiotics and supernatants of probiotic cultures were able to inhibit growth of two urinary tract pathogens. Probiotic mixtures prevented the growth of urinary tract pathogens but were not significantly more inhibitory than single strains. Probiotics appear to produce metabolites that are inhibitory towards urinary tract pathogens. Probiotics display potential to reduce the incidence of urinary tract infections via inhibition of colonisation.     

Does Probiotic Consumption Enhance Wound Healing? A Systematic Review

The use of probiotics is one of the emerging lines of treatment for wound healing. This systematic review aimed to summarize currently available evidence on the effect of oral or enteral probiotic therapy on skin or oral mucosal wound healing in humans. To verify the developments in this field and the level of available scientific evidence, we applied a broad search strategy with no restrictions on wound type, target population, probiotic strain, or intervention protocol used. This review included seven studies involving 348 individuals. Four studies reported positive outcomes for healing improvement after probiotic therapy, and none of the studies reported adverse effects or a marked increase in wound healing time. The positive or neutral results observed do not generate strong evidence regarding the effectiveness of probiotics for wound healing. However, they suggest a promising field for future clinical research where the probiotic strains used, type of wounds, and target population are controlled for.     

Cancer-preventing attributes of probiotics: an update

Cancer is a serious global public health problem. Cancer incidence and mortality have been steadily rising throughout the past century in most places of the world. There are several epidemiological evidences that support a protective role of probiotics against cancer. Lactic acid bacteria and their probioactive cellular substances exert many beneficial effects in the gastrointestinal tract, and also release various enzymes into the intestinal lumen and exert potential synergistic (LAB) effects on digestion and alleviate symptoms of intestinal malabsorption. Consumption of fermented dairy products with LAB may elicit anti-tumor effects. These effects are attributed to the inhibition of mutagenic activity, the decrease in several enzymes implicated in the generation of carcinogens, mutagens, or tumor-promoting agents, suppression of tumors, and epidemiology correlating dietary regimes and cancer. Specific cellular components in lactic acid bacteria seem to induce strong adjuvant effects including modulation of cell-mediated immune responses, activation of the reticulo-endothelial system, augmentation of cytokine pathways, and regulation of interleukins and tumor necrosis factors. Studies on the effect of probiotic consumption on cancer appear promising, since recent in vitro and in vivo studies have indicated that probiotic bacteria might reduce the risk, incidence and number of tumors of the colon, liver and bladder. The protective effect against cancer development may be ascribed to binding of mutagens by intestinal bacteria, may suppress the growth of bacteria that convert procarcinogens into carcinogens, thereby reducing the amount of carcinogens in the intestine, reduction of the enzymes β-glucuronidase and β-glucosidase and deconjugation of bile acids, or merely by enhancing the immune system of the host. There are isolated reports citing that administration of LAB results in increased activity of anti-oxidative enzymes or by modulating circulatory oxidative stress that protects cells against carcinogen-induced damage. These include glutathione-S-transferase, glutathione, glutathione reductase, glutathione peroxidase, superoxide dismutase and catalase. However, there is no direct experimental evidence for cancer suppression in human subjects as a result of the consumption of probiotic cultures in fermented or unfermented dairy products, but there is a wealth of indirect evidence based largely on laboratory studies.     

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.     

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.     

Emerging Roles of Probiotics in Prevention and Treatment of Breast Cancer: A Comprehensive Review of Their Therapeutic Potential

Breast cancer is the most common cancer among women. Need for novel preventive and curative approaches with more safety than the present one seems inevitable. This review is devoted to potentially favorable role of probiotics in prevention and treatment of breast cancer as well as their alleviating role regarding chemotherapy-induced side effects. Literature was searched for human, animal, and in vitro studies about the role of probiotics in breast cancer. In vitro studies showed that probiotic intervention induces cancer cells apoptosis and inhibits their proliferation. In animal models, treatment with probiotics inhibited tumor growth and reduced tumor size; also, the immunomodulatory, antiangiogenesis and antimetastatic activities of probiotics were illustrated. Human studies showed that intake of Lactobacillus casei shirota reduced the breast cancer incidence and consumption of fermented milk products and yogurt was inversely associated with breast cancer incidence; however, no study regarding the curative role of probiotics in breast cancer is available. Studies on the effect of probiotics on chemotherapy-induced side effects in breast cancer were contradictory but showed potential for more investigation. Probiotics seem to have a potential role in both prevention and treatment of breast cancer. However, more clinical studies are needed to elucidate their efficacy and safety.     

Comparative effects of six probiotic strains on immune function in vitro

There is considerable interest in the strain specificity of immune modulation by probiotics. The present study compared the immunomodulatory properties of six probiotic strains of different species and two genera in a human peripheral blood mononuclear cell (PBMC) model in vitro. Live cells of lactobacilli (Lactobacillus casei Shirota, L. rhamnosus GG, L. plantarum NCIMB 8826 and L. reuteri NCIMB 11951) and bifidobacteria (Bifidobacterium longum SP 07/3 and B. bifidum MF 20/5) were individually incubated with PBMC from seven healthy subjects for 24?h. Probiotic strains increased the proportion of CD69+ on lymphocytes, T cells, T cell subsets and natural killer (NK) cells, and increased the proportion of CD25+, mainly on lymphocytes and NK cells. The effects on activation marker expression did not appear to be strain specific. NK cell activity was significantly increased by all six strains, without any significant difference between strains. Probiotic strains increased production of IL-1β, IL-6, IL-10, TNF-α, granulocyte-macrophage colony-stimulating factor and macrophage inflammatory protein 1α to different extents, but had no effect on the production of IL-2, IL-4, IL-5 or TNF-β. The cytokines that showed strain-specific modulation included IL-10, interferon-γ, TNF-α, IL-12p70, IL-6 and monocyte chemotactic protein-1. The Lactobacillus strains tended to promote T helper 1 cytokines, whereas bifidobacterial strains tended to produce a more anti-inflammatory profile. The results suggest that there was limited evidence of strain-specific effects of probiotics with respect to T cell and NK cell activation or NK cell activity, whereas production of some cytokines was differentially influenced by probiotic strains.