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Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis.

BACKGROUND: We recently demonstrated that administration of probiotics resulted in significant clinical improvement in very young children with moderate-to-severe atopic dermatitis (AD). The purpose of this study was to determine the underlying immunological effects that are associated with these apparent clinical benefits. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from children (n = 53) at baseline and at the end of an 8-week supplementation period during which they received a probiotic (Lactobacillus fermentum PCCtrade mark) (n = 26) or a placebo (n = 27). A further sample was collected at 16 weeks (8 weeks after ceasing the supplement). Cytokine (IL-5, IL-6, IL-10, IL-13, IFN-gamma and TNF-alpha) responses to allergens (egg ovalbumin (OVA), beta lactoglobulin (BLG), house dust mite (HDM)), vaccines (tetanus toxoid (TT)), diphtheria toxoid (DT)), intestinal flora (heat-killed Lactobacillus (HKLB)), heat-killed Staphylococcus aureus (HKSA), Staphylococcus aureus enterotoxin B (SEB) and mitogen (phytohaemaglutinin (PHA)) were compared. RESULTS: The administration of probiotics was associated with a significant increase in T-helper type 1(Th1-type) cytokine IFN-gamma responses to PHA and SEB at the end of the supplementation period (week 8: P = 0.004 and 0.046) as well as 8 weeks after ceasing supplementation (week 16: P = 0.005 and 0.021) relative to baseline levels of response. No significant changes were seen in the placebo group. The increase in IFN-gamma responses to SEB was directly proportional to the decrease in the severity of AD (r = -0.445, P = 0.026) over the intervention period. At the end of the supplementation period (week 8) children receiving probiotics showed significantly higher TNF-alpha responses to HKLB (P = 0.018) and HKSA (P = 0.011) but this was no longer evident when supplementation ceased (week 16). Although IL-13 responses to OVA were significantly reduced in children receiving probiotics after 8 weeks (P = 0.008), there were no other effects on allergen-specific responses, and this effect was not sustained after ceasing supplementation (week 16). There were no effects on vaccine-specific responses, or on responses to any of the stimuli assessed. CONCLUSION: The improvement in AD severity with probiotic treatment was associated with significant increases in the capacity for Th1 IFN-gamma responses and altered responses to skin and enteric flora. This effect was still evident 2 months after the supplementation was ceased. The lack of consistent effects on allergen-specific responses suggests that the effects of probiotics may be mediated through other independent pathways, which need to be explored further.

Allergens↗

Representational difference analysis and real-time PCR for strain-specific quantification of Lactobacillus sobrius sp. nov.

Lactobacillus sobrius sp. nov., which was recently isolated from the intestine of weaning piglets, has potential probiotic properties. To follow the fate of L. sobrius strain 001T in dietary interventions, a novel and strain-specific quantitative detection procedure was developed. This procedure was based on the isolation of specific genomic fragments from the type strain by representational difference analysis and their detection by real-time PCR. The described strain-specific quantification approach may be used in studies aimed at tracking bacterial strains added to specific environments.

Animals↗

Anti-carcinogenicity of probiotics and prebiotics.

Yoghurt, and the lactic acid producing bacteria (LAB; probiotics) that it contains, have received much attention as potential cancer-preventing agents in the diet. It is usually considered that the mechanism of the action is by increasing the numbers of LAB in the colon, which modifies the ability of the microflora to produce carcinogens. Prebiotics such as non-digestible oligosaccharides (NDO) appear to have similar effects on the microflora by selectively stimulating the growth of LAB in the colon. Evidence for cancer-preventing properties of pro- and prebiotics is derived from studies on faecal enzyme activities in animals and humans, inhibition of genotoxicity of known carcinogens in vitro and In vivo, suppression of carcinogen-induced preneoplastic lesions and tumours in laboratory animals. Some of these studies indicate that combinations of pro and prebiotics ('synbiotics') are more effective. Epidemiological and intervention studies provide some, albelt limited, evidence for protective effects of products containing probiotics in humans.

Animals↗

Harnessing Probiotic LAB and Bacteriocins for Clean-Label Food Processing and Biopreservation: Omics, Molecular Innovations and Industrial Applications.

The persistence of microbial agents in foods, especially spore forming bacteria is one of the most significant challenges to food preservation and safety, undermining product quality, shelf life, and consumer health. The use of traditional control methods, including thermal processing and chemical preservatives, are increasingly limited by consumer demands for minimally processed foods, and the emergence of resistant microbial strains. Advances have been made in the use of probiotics like lactic acid bacteria (LAB) and their biometabolites like bacteriocins in food processing and preservation, particularly to control biofilm and endospore forming pathogens including Bacillus sp., Listeria sp., Staphylococcus sp., Clostridium sp., E. coli etc. in foods and food processing plants/surfaces. Given the ability of these organisms to cause foodborne illness and form resilient biofilms in the food processing ecosystem and their resistance to the conventional method of their elimination, the antimicrobial peptides (bacteriocins) are gaining increasing prominence as useful alternatives to synthetic antimicrobials in enhancing food safety and combating the threats of these pathogens. This review addresses current information on the inhibition of persistent microbial spoilage contaminants, biofilm-forming pathogens, and spore formers of interest to the food industry using LAB and their bacteriocins. Current developments in isolation, characterization, and mode of action of bacteriocins are explored, including synergistic activity with other preservative hurdle techniques such as encapsulation, and nanobiotechnology. Importantly, there is a focus on the utilization of molecular and omics-based approaches to enable a better understanding of bacteriocin biosynthesis, gene regulation, host-microbe interactions and gut microbiome regulation potential of probiotic LABs, permitting the rational development of targeted and strain-specific interventions. Developments in the incorporation of bacteriocin-producing LAB into functional starter cultures and bio-protective products, and challenges in stability, regulatory approval, and scalability for industrial use, are also discussed in the paper. Despite their considerable potential, broader translation remains constrained by regulatory requirements, production and formulation costs, variable efficacy in complex food matrices, and the limited validation of many candidate bacteriocins beyond laboratory and model-food systems. Collectively, these advances position LAB and their bacteriocins at the leading edge of developing sustainable, clean-label, and efficacious functional foods and food preservation systems. Their functionality can be expanded by integrating genomics, synthetic biology, and predictive modeling for the maximization of their biopreservative potential in diverse food matrices and in gut microbiota modulation.

Bioactive Peptides↗

Trophic status of the small intestine in young and aged rats: modulation by a yogurt-supplemented diet.

Among the multifactorial causes of undernutrition in old age, gastrointestinal mucosa altered function and resulting specific malabsorption are the most relevant. Despite numerous studies that have dealt with the effects of aging on the digestive tract of mammals, results showed discrepancies in terms of proliferation and biochemical aging small intestine events. However, the slowing-down of the maturation process and the poor adaptation of metabolism and intestinal function are obvious and there is evidence that protective mechanisms are impaired with age and contribute to affecting the trophic activity and related systemic homeostasis. Good prospects to improve gastrointestinal function in the elderly are essential and research on nutritional intervention to limit and counteract age-related impairments must be extensive. Probiotics are good candidates and fermented milks might be of great interest. In the present study we first show the main structural and functional variations between 3- and 23-month-old rat small intestines. The trophic consequences of aging and nutritional adaptation under basal conditions are also analyzed and discussed after 20 days of a yogurt-supplemented specific diet in both young and aged rats. The main variations that occur with aging and yogurt diet are located in the proximal small intestine. The present findings indicate a slight improvement of morphological trophic parameters in both young and aged rats by yogurt, whereas enzymatic changes are more discrete. Despite the obvious age-related decrease in trophicity, we suggest that assessment of probiotic potentials on trophicity requires a more altered model than normal, healthy aging animals.

Adaptation, Physiological↗

Benefits of early enteral nutrition with glutamine and probiotics in brain injury patients.

Brain injury patients have higher energy and protein expenditures and are prone to infections. The aim of the present study was to evaluate the results of early enteral feeding with glutamine and probiotics in brain injury patients. Twenty-three brain injury patients (Glasgow score between 5-12 and therapeutic intervention scoring system>20) were studied. Three patients were excluded to leave 20 remaining patients. Patients were randomized to receive either an early enteral diet (control group, n=10) or the same formula with glutamine and probiotics added (study group, n=10) for a minimum of 5 days (range, 5-14 days). The diets were isocaloric and isonitrogenous [35 kcal.kg(-1).day(-1) (where 1 kcal approximately 4.184 kJ) and 1.5 g of protein.kg(-1).day(-1)]. Main outcome measures were the incidence of infection, the length of stay in the intensive care unit and the number of days requiring mechanical ventilation. The two groups were homogeneous in gender, age, nutritional status and severity of trauma. There was no mortality during the study period. The infection rate was higher in controls (100%) when compared with the study group (50%; P=0.03) and the median (range) number of infections per patient was significantly greater (P<0.01) in the control group [3 (1-5)] compared with the study group [1 (0-3)]. Both the critical care unit stay [22 (7-57) compared with 10 (5-20) days; P<0.01; median (range)] and days of mechanical ventilation [14 (3-53) compared with 7 (1-15) days; P=0.04; median (range)] were higher in the patients in the control group than in the study group. We conclude that the enteral formula containing glutamine and probiotics decreased the infection rate and shortened the stay in the intensive care unit of brain injury patients.

Adult↗

Review article: the role of bacteria in onset and perpetuation of inflammatory bowel disease.

We review the evidence that strongly suggests a role of the intestinal microbiota in the onset and perpetuation of inflammatory bowel disease (IBD). Experimental studies consisted of suppressing micro-organisms from the microbiota (using germ-free or gnotoxenic animals or antibiotics), introducing new micro-organisms or microbial components (e.g. probiotics, CpG-DNA) or selectively increasing some endogenous bacteria (e.g. using prebiotics). Intervention studies were performed in patients or animal models of spontaneous or chemically-induced colitis. Information was also obtained from observational studies that described the composition of the faecal and mucosal microbiota at various stages of the disease process and in controls. Many have used culture-independent techniques that identify bacteria based on the nucleic acid sequence of ribosomal RNA molecules. Microbiota in patients with IBD seem to be characterized by high concentrations of bacteria in contact with the mucosa, instability, the presence of high numbers of unusual bacteria and sometimes a reduction in the biodiversity. Studies searching for a generalized or localized dysbiosis in IBD are discussed, as well as those trying to identify bacterial molecules and receptors, which may be implicated in triggering the inflammatory process.

Bacterial Infections↗

Probiotics and colon cancer.

Although a myriad of health-promoting effects have been attributed to the probiotic lactic acid bacteria, perhaps the most interesting and controversial is that of anticancer activity, the vast majority of studies in this area dealing with protective effects against colon cancer. There is no direct experimental evidence for cancer suppression in humans 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. Reports in the literature regarding the anticancer effects of lactic acid bacteria fall into the categories of in vitro studies, animal studies, epidemiological studies and human dietary intervention studies. Examples of these reports will be given in the current paper. The mechanisms by which probiotic bacteria may inhibit colon cancer are still poorly understood, but, several potential mechanisms are being discussed in the literature, and these will also be addressed in this review.

Animals↗

Nutritional issues in irritable bowel syndrome.

Food products have variously been reported as causing, perpetuating or treating irritable bowel syndrome. The evidence for this is reviewed with regard to recent studies investigating symptom reporting, mono- and disaccharide malabsorption and probiotics. The development of objective measures remains an urgent priority because of the high placebo response to any dietary intervention in irritable bowel syndrome.

Colon↗

Long-term consumption of fermented dairy products over 6 months increases HDL cholesterol.

OBJECTIVE: Assessment of the hypocholesterolaemic effect of yoghurt supplemented with Lactobacillus acidophilus 145 and Bifidobacterium longum 913 in women. DESIGN: The cross-over study consisted of three periods (7 weeks each): first period, control yoghurt for all 29 women; second period, probiotic yoghurt for 18 women, control yoghurt for 11 women; third period, the reverse of that in the second period. SETTING: Department of Nutritional Physiology, Institute of Nutritional Science, Friedrich Schiller University, Jena. SUBJECTS: Twenty-nine healthy women, aged 19-56 y. Fifteen of these were normocholesterolaemic and 14 women were hypercholesterolaemic. INTERVENTION: Yoghurt (300 g) daily containing 3.5% fat and starter cultures of Streptococcus thermophilus and L. lactis. Probiotic yoghurt was the control yoghurt enriched with L. acidophilus 145, B. longum 913 and 1% oligofructose (synbiotic). RESULTS: The mean serum concentration of total cholesterol and the LDL cholesterol was not influenced by the synbiotic (P>0.05). The HDL concentration increased significantly by 0.3 mmol/l (P=0.002). The ratio of LDL/HDL cholesterol decreased from 3.24 to 2.48 (P=0.001). CONCLUSIONS: The long-term daily consumption of 300 g yoghurt over a period of 21 weeks (control and synbiotic) increased the serum concentration of HDL cholesterol and lead to the desired improvement of the LDL/HDL cholesterol ratio.

Adult↗

The intestinal microflora in allergic Estonian and Swedish 2-year-old children.

BACKGROUND: The prevalence of allergic diseases seems to have increased particularly over the past 35-40 years. Furthermore, allergic disease is less common among children in the formerly socialist countries of central and Eastern Europe as compared with Western Europe. It has been suggested that a reduced microbial stimulation during infancy and early childhood would result in a slower postnatal maturation of the immune system and development of an optimal balance between TH1- and TH2-like immunity. AIMS: To test the hypothesis that allergic disease among children may be associated with differences in their intestinal microflora in two countries with a low (Estonia) and a high (Sweden) prevalence of allergy. METHODS: From a prospective study of the development of allergy in relation to environmental factors, 29 Estonian and 33 Swedish 2-year-old children were selected. They were either nonallergic (n = 36) or had a confirmed diagnosis of allergy (n = 27) as verified by typical history and at least one positive skin prick test to egg or cow's milk. Weighed samples of faeces were serially diluted (10-2-10-9) and grown under anaerobic conditions. The counts of the various genera and species were calculated for each child. In addition, the relative amounts of the particular microbes were expressed as a proportion of the total count. RESULTS: The allergic children in Estonia and Sweden were less often colonized with lactobacilli (P < 0.01), as compared with the nonallergic children in the two countries. In contrast, the allergic children harboured higher counts of aerobic micro-organisms (P < 0. 05), particularly coliforms (P < 0.01) and Staphylococcus aureus (P < 0.05). The proportions of aerobic bacteria of the intestinal flora were also higher in the allergic children (P < 0.05), while the opposite was true for anaerobes (P < 0.05). Similarly, in the allergic children the proportions of coliforms were higher (P < 0. 05) and bacteroides lower (P < 0.05) than in the nonallergic children. CONCLUSIONS: Differences in the indigenous intestinal flora might affect the development and priming of the immune system in early childhood, similar to what has been shown in rodents. The role of intestinal microflora in relation to the development of infant immunity and the possible consequences for allergic diseases later in life requires further study, particularly as it would be readily available for intervention as a means for primary prevention of allergy by the administration of probiotic bacteria.

Bacteria↗

Genetic basis of neonatal methicillin-resistant Staphylococcus aureus in Japan.

Methicillin-resistant Staphylococcus aureus (MRSA) is still one of major problems of drug-resistant microorganisms and healthcare-acquired infections. Methicillin-resistant Staphylococcus aureus is highly prevalent in patients in neonatal intensive care units (NICU) in Japan. The most predominant MRSA in NICU is multidrug resistant and produces superantigenic exotoxin, toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxin C (SEC). These predominant MRSA strains belong to coagulase type II, SCCmec type II, mecA-Tn554 polymorph type I-A and show closely related pulse field gel electrophoresis types. The dissemination of MRSA is wide, and there is a pandemic distribution of a single MRSA clone in the NICU of Japan. Since 1992, the nationwide spread of this clone has also led to the development of a new neonatal disease known as neonatal toxic shock-like exanthematous disease (NTED), which is caused by overactivation of vbeta2+ T cells induced by TSST-1. The spread of MRSA in NICU in Japan has been attributed to overcrowding, high rates of extremely low birthweight babies, understaffing, low control measures of infection and overuse of antibiotics. The environment of NICU and infection control intervention should be improved and a new strategy for control like vaccination or probiotics is required.

Bacterial Proteins↗

[Study of the influence of dietary yogurt in an allergic population].

BACKGROUND: Prevalence of allergic diseases has been increased in last years; new alternative therapies have been employed. Beneficial effects of probiotics have been described in some pathologies such as tumors, diarrhea, and allergic disease. The aim of our work was to describe nutritional status and influence of probiotic consumption in allergic population. PATIENTS AND METHODS: 44 allergic patients were selected, in all patients were recorded; sex, age, place of residence, anthropometric evaluation, dietary questionnaire and allergic variables (rush, blood levels of Ig E, and number of crisis in a year). RESULTS: 18 patients (40.9%) were females and 26 (59.1%) males with an average age of 24.5 (10.3) years. Most of patients (20.5%) are located in percentile P25-50, showing a good nutritional status. 16 patients consumed probiotics (27.1%), with an average of consumption per week 1.79 (3.16) and an average amount per week (mg-ml) (593.4 (461.9). The number of crisis year was 1.44 (1.8), average value of Ig E was 35.68 (31.93) UI/L and rush 10.09 (2.8) mm. Patients with a consumption of probiotics higher than 593 mg/week showed a IOW rush diameter (10.12(0.8) mm vs 8.85 (1.1) mm; p < 0.05), without statistical differences in other variables. CONCLUSION: Consumption of probiotics in allergic patients could be beneficial. Further studies with more patients and intervention designs will be necessary to analyze this relations.

Adult↗

Probiotics: a role in the treatment of intestinal infection and inflammation?

Probiotic therapy is based on the concept of normal healthy microflora. The development of novel means of characterising the gut microflora, in particular those based on the different levels of conservation in the ribosomal RNA sequences of different genera, have opened up new angles on the role of the gut microflora in health and disease. Components of the human intestinal microflora or organisms entering the intestine may have harmful or beneficial effects on human health. Abundant evidence implies that specific strains selected from the healthy gut microflora exhibit powerful antipathogenic and anti-inflammatory capabilities, and are consequently involved with enhanced colonisation resistance in the intestine. Realisation of this has led to the introduction of novel modes of therapeutic and prophylactic intervention based on the consumption of mono and mixed cultures of beneficial live microorganisms as probiotics.

Acute Disease↗

Probiotic supplementation increases fecal TLR4 agonists without improving disease activity in juvenile idiopathic arthritis: a randomized placebo-controlled trial.

Gut dysbiosis has been implicated in the pathogenesis of juvenile idiopathic arthritis (JIA), suggesting that microbiota-targeted interventions may influence immune signalling during early immune development. We conducted the PERMAJI multicentre randomized, double-blind, placebo-controlled trial to evaluate the effects of probiotic supplementation (VSL#3) on host-microbiota immune interactions and disease activity in children with oligoarticular or RF-negative polyarticular JIA. Participants were randomly assigned (1:1) to receive VSL#3 or placebo for 3 months in addition to standard therapy. Stool and serum samples collected at baseline and month 3 were used to assess gut microbiota composition, fecal innate immune agonists, intestinal permeability, and systemic cytokines. The primary clinical endpoint was the proportion achieving an ACR Pedi 30 response at 3 months. Forty-four children were enrolled between September 2017 and July 2022. Clinical responses did not differ between groups (ACR Pedi 30: 47% with VSL#3 vs 63% with placebo; p&#x2009;=&#x2009;0.33), and conservative worst-case assumptions for missing data suggested lower response rates with VSL#3 (36% vs 68%; p&#x2009;=&#x2009;0.03). Probiotic supplementation significantly increased fecal Toll-like receptor 4 (TLR4) agonist activity, whereas gut microbiota diversity, intestinal permeability, and systemic cytokine levels remained unchanged. These findings indicate that probiotic supplementation can modify microbial innate immune signalling without detectable changes in microbial community diversity and may increase exposure to pro-inflammatory microbial stimuli in early-life autoimmune disease. The results highlight the complexity of host-microbiota immune interactions and underscore the need for careful evaluation of microbiome-targeted therapies in paediatric autoimmune disorders.

Humans↗

Role of nutritional intervention in patients treated with radiotherapy for pelvic malignancy.

Up to 12000 patients with gynaecological, urological and rectal cancer undergo radical pelvic radiotherapy annually in the UK. More than 70% develop acute inflammatory changes causing gastrointestinal symptoms during treatment because healthy bowel tissue is encompassed in the radiation field. In total, 50% go on to develop chronic bowel symptoms, which affect quality of life due to permanent changes in the small and large intestine. Nutritional intervention may influence acute and chronic bowel symptoms but the validity of the advice given to patients is not clear. To assess the incidence and significance of malnutrition and to examine the efficacy of therapeutic nutritional interventions used to manage gastrointestinal side effects in patients undergoing pelvic radiotherapy and those with chronic bowel side effects after treatment, a critical review of relevant original studies on human subjects was carried out using a specific set of mesh terms in MEDLINE and EMBASE databases and the Cochrane Library in September 2003. Full texts of all relevant articles were collected and reference lists were checked. Sources of grey literature including conference abstracts and web-based information were also reviewed. A total of 36 papers published in peer-reviewed journals between 1966 and 2003 were identified. In all, 14 randomised controlled trials, 12 prospective cohorts, four retrospective, two qualitative, one validation, one pilot study and two case reports were obtained. These included 2646 patients. Eight articles including three conference abstracts and web-based information were found. None of the studies was definitive because of weakness in methodology. No studies could be combined because the interventions and the end points were different. There is no evidence base for the use of nutritional interventions to prevent or manage bowel symptoms attributable to radiotherapy. Low-fat diets, probiotic supplementation and elemental diet merit further investigation.

Diarrhea↗

Comparison of fecal microflora in children with atopic eczema/dermatitis syndrome according to IgE sensitization to food.

Atopic eczema/dermatitis syndrome (AEDS) commonly often arises during early infancy. In several intervention studies a beneficial influence on AEDS course of certain intestinal bacteria, administered as 'probiotics', has been described. To evaluate the possible role of the natural intestinal microflora in children with allergic eczema/dermatitis syndrome regarding immediate type hypersensitivity to food allergens, children with food allergy (AAEDS, n = 68) have been compared with children without detectable food allergy (NAEDS, n = 25). All children (n = 93) in preschool age, mean age of 2.6 (+/-1.8) years, diagnosed with AEDS who were treated as inpatients in 2003 in a dermatological hospital were included. The correlation between fecal microflora, parasites and specific immunoglobulin E (IgE) antibodies against common food allergens was analyzed. A similar composition of intestinal microflora in children with AAEDS and NAAEDS was found. The food allergens that were most frequently detected were egg white, cow milk, casein, peanut and hazelnut. Furthermore, a significant association between IgE sensitization against important food allergens and components of the fecal microflora could not be demonstrated. With aging changes occur in the intestinal microbiota [Proteus/Klebsiella and age (rho = -0.607) and Enterococcus and age (rho = -0.428)]. In two subjects of the AAEDS group Blastocystis hominis was found. The composition of natural intestinal microflora in children with AAEDS and NAAEDS was similar. Hence, there is no evidence of a role of the intestinal microflora with regard to the development of infant (food) allergy in children with AEDS. The possible consequences for allergic diseases later in life require further investigation.

Antibody Specificity↗