The gut microbiota and host health: a new clinical frontier.

Over the last 10-15 years, our understanding of the composition and functions of the human gut microbiota has increased exponentially. To a large extent, this has been due to new 'omic' technologies that have facilitated large-scale analysis of the genetic and metabolic profile of this microbial community, revealing it to be comparable in influence to a new organ in the body and offering the possibility of a new route for therapeutic intervention. Moreover, it might be more accurate to think of it like an immune system: a collection of cells that work in unison with the host and that can promote health but sometimes initiate disease. This review gives an update on the current knowledge in the area of gut disorders, in particular metabolic syndrome and obesity-related disease, liver disease, IBD and colorectal cancer. The potential of manipulating the gut microbiota in these disorders is assessed, with an examination of the latest and most relevant evidence relating to antibiotics, probiotics, prebiotics, polyphenols and faecal microbiota transplantation.

Nutritional advice for community patients: insights from a panel discussion.

This article describes the conclusions of an expert panel that discussed four case studies; these were examples of patients typically encountered by nurses working in the community. The panel considered the nutritional and lifestyle advice that could be given by nurses relating to conditions such as irritable bowel syndrome (IBS), depression, chronic fatigue syndrome, vulnerability to common infections, elderly care, recurrent urinary tract infection, antibiotic use, and risk of type 2 diabetes. A general conclusion was the importance of motivational interviewing techniques in achieving full understanding of patients' concerns and to determine the best health strategy. As well as specific guidance appropriate for each disorder, a range of information sources for both health professionals and patients are listed in the paper. The panel noted that, although general nutritional advice can be given by nurses working at GP surgeries and in the community, patients should always be referred to registered dietitians or nutritionists if significant dietary changes are considered.

Probiotics: a proactive approach to health. A symposium report.

This report summarises talks given at the 8th International Yakult Symposium, held on 23-24 April 2015 in Berlin. Two presentations explored different aspects of probiotic intervention: the small intestine as a probiotic target and inclusion of probiotics into integrative approaches to gastroenterology. Probiotic recommendations in gastroenterology guidelines and current data on probiotic efficacy in paediatric patients were reviewed. Updates were given on probiotic and gut microbiota research in obesity and obesity-related diseases, the gut-brain axis and development of psychobiotics, and the protective effects of equol-producing strains for prostate cancer. Recent studies were presented on probiotic benefit for antibiotic-associated diarrhoea and people with HIV, as well as protection against the adverse effects of a short-term high-fat diet. Aspects of probiotic mechanisms of activity were discussed, including immunomodulatory mechanisms and metabolite effects, the anti-inflammatory properties of Faecalibacterium prausnitzii, the relationship between periodontitis, microbial production of butyrate in the oral cavity and ageing, and the pathogenic mechanisms of Campylobacter. Finally, an insight was given on a recent expert meeting, which re-examined the probiotic definition, advised on the appropriate use and scope of the term and outlined different probiotic categories and the prevalence of different mechanisms of activity.

Exploring the influence of the gut microbiota and probiotics on health: a symposium report.

The present report describes the presentations delivered at the 7th International Yakult Symposium, 'The Intestinal Microbiota and Probiotics: Exploiting Their Influence on Health', in London on 22-23 April 2013. The following two themes associated with health risks were covered: (1) the impact of age and diet on the gut microbiota and (2) the gut microbiota's interaction with the host. The strong influence of the maternal gut microbiota on neonatal colonisation was reported, as well as rapid changes in the gut microbiome of older people who move from community living to residential care. The effects of dietary changes on gut metabolism were described and the potential influence of inter-individual microbiota differences was noted, in particular the presence/absence of keystone species involved in butyrate metabolism. Several speakers highlighted the association between certain metabolic disorders and imbalanced or less diverse microbiota. Data from metagenomic analyses and novel techniques (including an ex vivo human mucosa model) provided new insights into the microbiota's influence on coeliac, obesity-related and inflammatory diseases, as well as the potential of probiotics. Akkermansia muciniphila and Faecalibacterium prausnitzii were suggested as targets for intervention. Host-microbiota interactions were explored in the context of gut barrier function, pathogenic bacteria recognition, and the ability of the immune system to induce either tolerogenic or inflammatory responses. There was speculation that the gut microbiota should be considered a separate organ, and whether analysis of an individual's microbiota could be useful in identifying their disease risk and/or therapy; however, more research is needed into specific diseases, different population groups and microbial interventions including probiotics.

Immunomodulatory effects of a probiotic drink containing Lactobacillus casei Shirota in healthy older volunteers.

PURPOSE: There is growing evidence that probiotics confer health benefits to the host by modulating immune function, especially in older people, where immunosenescence is a feature even of healthy ageing. The aim of this study was to investigate the effect of a probiotic drink containing Lactobacillus casei Shirota (LcS) on immune function in a healthy non-immunocompromised older population. METHODS: Thirty healthy old volunteers were recruited into a randomized placebo-controlled, single-blind crossover study. The volunteers were supplemented with the probiotic drink containing 1.3 × 10(10) CFU LcS or skimmed milk per day for 4 weeks, followed by 4 weeks of washout and were crossed over to the other treatment. Peripheral blood and saliva samples were collected at baseline and end of each treatment. RESULTS: Probiotic consumption was associated with a significant increase in natural killer (NK) cell activity relative to baseline and a significant decrease in the mean fluorescence intensity of CD25 expression in the resting T cells compared with placebo. Additionally, there was a trend towards an increased ratio of IL-10 to IL-12 relative to baseline after LcS intake. CONCLUSIONS: Consumption of a probiotic drink containing LcS improved NK cell activity and tended to produce a more anti-inflammatory cytokine profile in an older population.

Dysregulated circulating dendritic cell function in ulcerative colitis is partially restored by probiotic strain Lactobacillus casei Shirota.

BACKGROUND: Dendritic cells regulate immune responses to microbial products and play a key role in ulcerative colitis (UC) pathology. We determined the immunomodulatory effects of probiotic strain Lactobacillus casei Shirota (LcS) on human DC from healthy controls and active UC patients. METHODS: Human blood DC from healthy controls (control-DC) and UC patients (UC-DC) were conditioned with heat-killed LcS and used to stimulate allogeneic T cells in a 5-day mixed leucocyte reaction. RESULTS: UC-DC displayed a reduced stimulatory capacity for T cells (P < 0.05) and enhanced expression of skin-homing markers CLA and CCR4 on stimulated T cells (P < 0.05) that were negative for gut-homing marker ß7. LcS treatment restored the stimulatory capacity of UC-DC, reflecting that of control-DC. LcS treatment conditioned control-DC to induce CLA on T cells in conjunction with ß7, generating a multihoming profile, but had no effects on UC-DC. Finally, LcS treatment enhanced DC ability to induce TGFß production by T cells in controls but not UC patients. CONCLUSIONS: We demonstrate a systemic, dysregulated DC function in UC that may account for the propensity of UC patients to develop cutaneous manifestations. LcS has multifunctional immunoregulatory activities depending on the inflammatory state; therapeutic effects reported in UC may be due to promotion of homeostasis.

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.

Interactions of nisin with glutathione in a model protein system and meat.

Loss of nisin activity in meat has been ascribed, in part, to the formation of a nisin-glutathione adduct. Activity is lost more quickly in raw meat than in cooked meat, and this has been taken as evidence that the reaction is enzyme mediated. Formation of the nisin-glutathione adduct has been confirmed but is shown not to be enzyme mediated. Retention of activity in cooked meat is shown to be due to the loss of free sulfhydryl groups during cooking as a result of the reaction of glutathione with proteins and not a result of the inactivation of endogenous enzymes. Microbial enzymes do not appear to play a role, as similar losses are seen in raw and cooked meat extracts, both of which contained undetectable levels of microorganisms.

Investigation of the effectiveness of Ascopyrone P as a food preservative.

Ascopyrone P (APP), a novel antibacterial from fungi, was evaluated as a food preservative. Efficacy was generally assessed by comparing the time taken for test strains to grow to 10(6) CFU/g in food +/- APP. In chilled chicken soup, 2000 mg kg-1 APP prevented Bacillus cereus, Listeria monocytogenes, Pseudomonas fluorescens, Salmonella and Escherichia coli reaching this threshold for >60 days. Good activity was also observed at 500-1000 mg kg-1 but not against L. monocytogenes. No activity was observed against Saccharomyces cerevisiae. Activity was reduced at 20 degrees C, although 2000 mg kg-1 was still effective against B. cereus and P. fluorescens. APP was less effective in chilled cooked meat systems and ineffective in raw meat. In a cooked meat system at 8 degrees C, bacteriostatic effect was generally observed at 2000 mg kg-1 against Salmonella typhimurium, E. coli and P. fluorescens but not against L. monocytogenes or Lactobacillus sake. Activity against Gram-negative enteric bacteria was enhanced by low temperature. In milk, 2000 mg l-1 was effective against P. fluorescens at chilled but not ambient temperature. APP was ineffective against yeasts and the mould Byssochlamys in apple juice. A minimum of 2000 mg kg-1 APP would appear to be necessary for antibacterial efficacy in food, although low-temperature storage may help. Observed variations in sensitivity may be related to APP stability, which decreases >pH 5.5. Toxicology testing is needed before consideration of APP for food use.

Effective use of nisin to control Bacillus and Clostridium spoilage of a pasteurized mashed potato product.

Heat-resistant spore-forming bacteria such as Bacillus and Clostridium can survive and grow in cooked potato products. This situation represents both a public health problem and an economic problem. The natural food preservative nisin is used in heat-treated foods to prevent the growth of such bacteria. A cocktail of Clostridium sporogenes and Clostridium tyrobutyricum spores was inoculated into cooked mashed potatoes, which were vacuum packed, pasteurized, and incubated at 8 and 25 degrees C. The shelf life of the mashed potatoes at 25 degrees C was extended by at least 58 days with the addition 6.25 microg of nisin per g. At 8 degrees C, in control samples not containing nisin, the natural contaminant Bacillus grew, but the inoculated Clostridium strains did not until the temperature was raised to 20 degrees C after 39 days. No bacterial growth occurred in nisin-containing samples. The shelf life of the mashed potatoes was extended by at least 30 days with 6.25 microg of nisin per g. In trials involving a cocktail of Bacillus cereus and Bacillus subtilis strains, 6.25 microg of nisin per g extended the shelf life of mashed potato samples that were not vacuum packed by at least 27 days at 8 degrees C. At 25 degrees C, 25 microg of nisin per g extended shelf life by a similar period. Shelf life extension was also observed at lower nisin levels. Microbiological analysis of the mashed potato ingredients showed that a high spore level was associated with the onion powder. It is emphasized that the preservative and the ingredients must be well mixed to ensure good nisin efficacy. Nisin remained at effective levels after pasteurization, and good retention was observed throughout the shelf life of the mashed potatoes.

Human gut dendritic cells drive aberrant gut-specific t-cell responses in ulcerative colitis, characterized by increased IL-4 production and loss of IL-22 and IFNγ.

: The pathogenesis of inflammatory bowel disease is incompletely understood but results from a dysregulated intestinal immune response to the luminal microbiota. CD4 T cells mediate tissue injury in the inflammatory bowel disease-associated immune response. Dendritic cells (DC) generate primary T-cell responses and mediate intestinal immune tolerance to prevent overt inflammation in response to the gut microbiota. However, most information regarding function of intestinal DC has come from mouse models, and information in humans is scarce. We show here that intestinal DC subsets are skewed in ulcerative colitis (UC) in humans, with a loss of CD103 lymph-node homing DC; this intestinal DC subset preferentially generates regulatory T cells in mice. We show infiltrates of DC negative for myeloid marker CD11c, with enhanced expression of Toll-like receptors for bacterial recognition. After mixed leukocyte reaction, DC from the inflamed UC colon had an enhanced ability to generate gut-specific CD4 T cells with enhanced production of interleukin-4 but a loss of interferon γ and interleukin-22 production. Conditioning intestinal DC with probiotic strain Lactobacillus casei Shirota in UC partially restored their normal function indicated by reduced Toll-like receptor 2/4 expression and restoration of their ability to imprint homing molecules on T cells and to generate interleukin-22 production by stimulated T cells. This study suggests that T-cell dysfunction in UC is driven by DC. T-cell responses can be manipulated indirectly through effects of bacterial conditioning on gut DC with implications for immunomodulatory effects of the commensal microbiota in vivo. Manipulation of DC to allow generation of DC-specific therapy may be beneficial in inflammatory bowel disease.

Spatial interactions between subsurface bacterial colonies in a model system: a territory model describing the inhibition of Listeria monocytogenes by a nisin-producing lactic acid bacterium.

The effect of spatial separation on interactions between subsurface bacterial colonies was tested using a model system: the inhibition of Listeria monocytogenes by nisin-producing and nisin-non-producing Lactococcus lactis subsp. lactis. Separation distance was controlled by altering the number of inoculum organisms within the agar. Mean separation distance was calculated by determining the mean volume available to each cell at the start of the experiment. Inhibition was assessed by comparing the growth of L. monocytogenes in pure culture with its growth in the presence of Lac. lactis subsp. lactis. Increasing the distance between colonies resulted in an exponential decrease in inhibition. When L. monocytogenes and Lac. lactis subsp. lactis colonies were within 100 microns of each other, the increase in cell numbers per L. monocytogenes colony was only 0.6 c.f.u. (which indicated some cells had become non-viable). This was a log reduction of 3.5 compared to the pure culture control. A separation distance of 1000 microns resulted in a L. monocytogenes colony growth increment of 2.5 x 10(2) c.f.u. per colony, a log reduction of 3.0 compared to the control. Increasing the separation distance to 3000 microns resulted in a L. monocytogenes colony growth increment of 1.3 x 10(6) c.f.u. per colony, a log reduction of 0.9 compared to the control. The effects of nisin and acidity were investigated by using a nisin-non-producing strain of Lac. lactis subsp. lactis and by buffering the medium. Data were obtained for the effect of separation on inhibition, as well as competition between colonies of the same species. The inhibition was mathematically described in terms of a simplified 'territory' model of immobilized bacterial growth. There was a strong qualitative agreement between the mathematical model and the experimental data. It was concluded that the phenomenon of propinquity is of important consideration when modeling and predicting microbial growth within solid food systems.