Systemic gut microbial modulation of bile acid metabolism in host tissue compartments

We elucidate the detailed effects of gut microbial depletion on the bile acid sub-metabolome of multiple body compartments (liver, kidney, heart, and blood plasma) in rats. We use a targeted ultraperformance liquid chromatography with time of flight mass-spectrometry assay to characterize the differential primary and secondary bile acid profiles in each tissue and show a major increase in the proportion of taurine-conjugated bile acids in germ-free (GF) and antibiotic (streptomycin/penicillin)-treated rats.Although conjugated bile acids dominate the hepatic profile (97.0 ± 1.5%) of conventional animals, unconjugated bile acids comprise the largest proportion of the total measured bile acid profile in kidney (60.0±10.4%) andheart (53.0 ± 18.5%) tissues. In contrast, in the GF animal, taurine-conjugated bile acids (especially taurocholic acid and tauro-β-muricholic acid) dominated the bile acid profiles (liver: 96.0 ± 14.5%; kidney: 96 ± 1%; heart: 93 ± 1%; plasma: 93.0 ± 2.3%), with unconjugated and glycine-conjugated species representing a small proportion of the profile. Higher free taurine levels were found in GF livers compared with the conventional liver (5.1-fold; P < 0.001). Bile acid diversity was also lower in GF and antibiotic-treated tissues compared with conventional animals. Because bile acids perform important signaling functions, it is clear that these chemical communication networks are strongly influencedbymicrobial activitiesormodulation, as evidenced by farnesoid X receptor-regulated pathway transcripts. The presence of specific microbial bile acid co-metabolite patterns in peripheral tissues (including heart and kidney) implies a broader signaling role for these compounds and emphasizes the extent of symbiotic microbial influences in mammalian homeostasis.

The 'direct costs' of livestock disease: The development of a system of models for the analysis of 30 endemic livestock diseases in Great Britain

The 'direct costs' attributable to 30 different endemic diseases of farm animals in Great Britain are estimated using a standardised method to construct a simple model for each disease that includes consideration of disease prevention and treatment costs. The models so far developed provide a basis for further analyses including cost-benefit analyses for the economic assessment of disease control options. The approach used reflects the inherent livestock disease information constraints, which limit the application of other economic analytical methods. It is a practical and transparent approach that is relatively easily communicated to veterinary scientists and policy makers. The next step is to develop the approach by incorporating wider economic considerations into the analyses in a way that will demonstrate to policy makers and others the importance of an economic perspective to livestock disease issues.

Updated estimates of the costs associated with thirty four endemic livestock diseases in Great Britain: A note

This Note outlines the further development of a system of models for the estimation of the costs of livestock diseases first presented by Bennett (2003). The models have been developed to provide updated and improved estimates of the costs associated with 34 endemic diseases of livestock in Great Britain, using border prices and including assessments of the impact of diseases on human health and animal welfare. Results show that, of the diseases studied, mastitis has the highest costs for cattle diseases, enzootic abortion for sheep diseases, swine influenza for pig diseases and salmonellosis for poultry diseases.

The survival advantage of milk and dairy consumption: An overview of evidence from cohort studies of vascular diseases, diabetes and cancer

Objectives: To conduct it detailed evaluation, with meta-analyses, of the published evidence on milk and dairy consumption and the incidence of vascular diseases and diabetes. Also to summarise the evidence on milk and dairy consumption and cancer reported by the World Cancer Research Fund and then to consider the relevance of milk and dairy consumption to survival in the UK, a typical Western community. Finally, published evidence on relationships with whole milk and fat-reduced milks was examined. Methods: Prospective cohort studies of vascular disease and diabetes with baseline data on milk or dairy consumption and a relevant disease outcome were identified by searching MEDLINE, and reference lists in the relevant published reports. Meta-analyses of relationships in these reports were conducted. The likely effect of milk and dairy consumption on survival was then considered, taking into account the results of published overviews of relationships of these foods with cancer. Results: From meta-analysis of 15 studies the relative risk of stroke and/or heart disease in subjects with high milk or dairy consumption was 0.84 (95% CI 0.76, 0,93) and 0.79 (0.75, 0.82) respectively, relative to the risk in those with low consumption. Four studies reported incident diabetes as an outcome, and the relative risk in the Subjects with the highest intake of milk or diary foods was 0.92 (0.86, 0.97). Conclusions: Set against the proportion of total deaths attributable to the life-threatening diseases in the UK, vascular disease, diabetes and cancer, the results of meta-analyses provide evidence of an overall survival advantage from the consumption of milk and dairy foods.

Influence of foliar diseases and their control by fungicides on grain yield and quality in wheat

Twenty-eight field experiments on sandy-loam soils in the UK (1982-2003) are reviewed by relating the extension of the green area duration of the flag leaf (GLADF) by fungicides to effects on yield and quality of winter wheat. Over all experiments mean grain yield = 8.85t ha(-1) at 85% DM. With regards quality, mean values were: thousand grain weight (TGW) = 44.5 g; specific weight (SWT) = 76.9 kg hl(-1); crude protein concentration (CP (N x 5.7)) = 12.5 % DM; Hagberg falling number (HFN) = 285 s; and sodium dodecyl sulphate (SDS)-sedimentation volume = 69ml. For each day (d) that fungicides increased GLADF there were associated average increases in yield (0.144 1 ha(-1) d(-1), se 0.0049, df = 333), TGW (0.56 gd(-1), se = 0.017) and SWT (0.22 kg hl(-1) d(-1), se 0.011). Some curvature was evident in all these relationships. When GLADF was delayed beyond 700 degrees Cd after anthesis, as was possible in cool wet seasons, responses were curtailed, or less reliable. Despite this apparent terminal sink limitation, fungicide effects on sink size, eg endosperm cell numbers or maximum water mass per grain, were not prerequisites for large effects on grain yield, TGW or SWT. Fungicide effects on CP were variable. Although the average response of CP was negative (-0.029%DM/d; se = 0.00338), this depended on cultivar and disease controlled. Controlling biotrophs such as rusts, (Puccinia spp.) tended to increase CP, whereas controlling a more necrotrophic pathogen (Septoria tritici) usually reducedCP. Irrespective of pathogen controlled, delaying senescence of the flag leaf was associated with increased nitrogen yields in the grain (averaging 2.24 kg N ha-1 d(-1), se = 0.0848) due to both increased N uptake into the above ground crop, and also more efficient remobilisation of N from leaf laminas. When sulphur availability appeared to be adequate, fungicide x cultivar interactions were similar on S as for CP, although N:S ratios tended to decline (i.e. improve for bread making) when S. tritici was controlled. On average, SDS-sedimentation volume declined (-0. 18 ml/d, se = 0.027) with increased GLADF, broadly commensurate with the average effect on CP. Hagberg falling number decreased as fungicide increased GLADF (-2.73 s/d, se = 0.178), indicating an increase in alpha-amylase activity.

Systemic and persistent effect of neem (Azadirachta indica) formulations against root-knot nematodes, Meloidogyne javanica and their storage life

Neem leaves, neem cake (a by-product left after the extraction of oil from neem seed) and a commercially refined product aza (azadirachtin) extracted from seed were evaluated. Aqueous extracts of crude neem formulations used as a seedling dip treatment significantly reduced the number of females and egg masses in roots whereas the refined one did not. A split-root technique was used to demonstrate the translocation of active compounds within a plant and their subsequent effect on the development of nematodes. When applied to the root portion all formulations significantly reduced the number of egg masses and eggs per egg mass. Whereas on the untreated root portion, neem cake at 3% w/w and aza at 0.1% w/w significantly reduced the number of egg masses as compared with neem leaves at 3% w/w, aza at 0.05% and control. All the neern formulations significantly reduced the number of eggs per egg mass on' the untreated root portion. The effect of neem leaves and cake on the development of root-knot nematodes was tested at 2, 4, 6, 8, and 16 weeks after their application to soil. Even after 16 weeks all the treatments significantly reduced the galling index and number of egg masses but their effectiveness declined over time. After storing neem leaves, cake and aza for 8 months under ambient conditions the efficacy of neem leaves and aza, against root-knot nematodes, remained stable whereas that of cake declined. (c) 2006 Elsevier Ltd. All rights reserved.

Enhancement of germination of spores of Verticillium dahliae and Fusarium oxysporum esp vasinfectum in vascular fluid from cotton plants infected with the root-knot nematode

Root-knot nematode [RKN] (Meloidogyne incognita) can increase the severity of Verticillium (V dahliae) and Fusarium (F oxysporum f.sp. vasinfectum) wilt diseases in cotton (Gossypium hirsutum). This study was conducted to determine some of the physiological responses caused by nematode invasion that might decrease resistance to vascular wilt diseases. The effect of RKN was investigated on spore germination and protein, carbohydrate and peroxidase content in the xylem fluids extracted from nematode-infected plants. Two cotton cultivars were used with different levels of resistance to both of the wilt pathogens. Spore germination was greater in the xylem fluids from nematode-infected plants than from nematode-free plants. The effect on spore germination was greater in the Fusarium-resistant cultivar (51%). Analysis of these fluids showed a decrease in total protein and carbohydrate levels for both wilt-resistant cultivars, and an increase in peroxidase concentration. Fluids from nematode-free plants of the Verticillium-resistant cultivar contained 46% more peroxidase than the Fusarium-resistant cultivar. The results provide further evidence that the effect of RKN on vascular wilt resistance is systemic and not only local. Changes in metabolites in the xylem pass from the root to the stem, accelerating disease development.

Field evaluation of systemic inducing resistance chemicals at different growth stages for the control of apple (Venturia inaequalis) and pear (Venturia pirina) scab

Two field trials were conducted using established apple (Malus cv. Golden Delicious) and pear (Pyrus communis 'Williams' Bon Chretien') to assess the efficacy of three commercially available systemic inducing resistance (SIR) products, Messenger (a.i. Harpin protein), Phoenix (a.i. Potassium phosphite) and Rigel (a.i. Salicylic acid derivative) applied at four different growth stages of tree development (bud break, green cluster, 90% petal fall, early fruitlet) against the foliar pathogens Venturia inaequalis and Venturia pirina which cause apple and pear scab respectively. A conventional synthetic fungicide (penconazole) used within the UK for apple and pear scab control was included for comparison. Little efficacy as scab protectants was demonstrated when each SIR product and penconazole was applied at only two growth stages (bud break, green cluster). However when the above compounds were applied at three or more growth stages efficacy as scab protectants was confirmed. The synthetic fungicide penconazole provided greatest protection against apple and pear scab in both the 2006 and 2007 field trials. There was little difference in the magnitude of scab protection conferred by each SIR agent. Results suggest application of at least three sprays during bud break to early fruitlet formation with an appropriate SIR agent may provide a useful addition to existing methods of apple and pear scab management under field conditions. (C) 2009 Published by Elsevier Ltd.

Effects of straw and silicon soil amendments on some foliar and stem-base diseases in pot-grown winter wheat

Four foliar and two stem-base pathogens were inoculated onto wheat plants grown in different substrates in pot experiments. Soils from four different UK locations were each treated in three ways: (i) straw incorporated in the field at 10 t ha−1 several months previously; (ii) silicon fertilization at 100 mg L−1 during the experiment; and (iii) no amendments. A sand and vermiculite mix was used with and without silicon amendment. The silicon treatment increased plant silica concentrations in all experiments, but incorporating straw was not associated with raised plant silica concentrations. Blumeria graminis and Puccinia recondita were inoculated by shaking infected plants over the test plants, followed by suitable humid periods. The silicon treatment reduced powdery mildew (B. graminis) substantially in sand and vermiculite and in two of the soils, but there were no effects on the slight infection by brown rust (P. recondita). Phaeosphaeria nodorum and Mycosphaerella graminicola were inoculated as conidial suspensions. Leaf spot caused by P. nodorum was reduced in silicon-amended sand and vermiculite; soil was not tested. Symptoms of septoria leaf blotch caused by M. graminicola were reduced by silicon amendment in a severely infected sand and vermiculite experiment but not in soil or a slightly infected sand and vermiculite experiment. Oculimacula yallundae (eyespot) and Fusarium culmorum (brown foot rot) were inoculated as agar plugs on the stem base. Severity of O. yallundae was reduced by silicon amendment of two of the soils but not sand and vermiculite; brown foot rot symptoms caused by F. culmorum were unaffected by silicon amendment. The straw treatment reduced severity of powdery mildew but did not detectably affect the other pathogens. Both straw and silicon treatments appeared to increase plant resistance to all diseases only under high disease pressure.

New scientific paradigms for probiotics and prebiotics

The inaugural meeting of the International Scientific Association for Probiotics and Prebiotics (ISAPP) was held May 3 to May 5 2002 in London, Ontario, Canada. A group of 63 academic and industrial scientists from around the world convened to discuss current issues in the science of probiotics and prebiotics. ISAPP is a non-profit organization comprised of international scientists whose intent is to strongly support and improve the levels of scientific integrity and due diligence associated with the study, use, and application of probiotics and prebiotics. In addition, ISAPP values its role in facilitating communication with the public and healthcare providers and among scientists in related fields on all topics pertinent to probiotics and prebiotics. It is anticipated that such efforts will lead to development of approaches and products that are optimally designed for the improvement of human and animal health and well being. This article is a summary of the discussions, conclusions, and recommendations made by 8 working groups convened during the first ISAPP workshop focusing on the topics of: definitions, intestinal flora, extra-intestinal sites, immune function, intestinal disease, cancer, genetics and genomics, and second generation prebiotics. Humans have evolved in symbiosis with an estimated 1014 resident microorganisms. However, as medicine has widely defined and explored the perpetrators of disease, including those of microbial origin, it has paid relatively little attention to the microbial cells that constitute the most abundant life forms associated with our body. Microbial metabolism in humans and animals constitutes an intense biochemical activity in the body, with profound repercussions for health and disease. As understanding of the human genome constantly expands, an important opportunity will arise to better determine the relationship between microbial populations within the body and host factors (including gender, genetic background, and nutrition) and the concomitant implications for health and improved quality of life. Combined human and microbial genetic studies will determine how such interactions can affect human health and longevity, which communication systems are used, and how they can be influenced to benefit the host. Probiotics are defined as live microorganisms which, when administered in adequate amounts confer a health benefit on the host.1 The probiotic concept dates back over 100 years, but only in recent times have the scientific knowledge and tools become available to properly evaluate their effects on normal health and well being, and their potential in preventing and treating disease. A similar situation exists for prebiotics, defined by this group as non-digestible substances that provide a beneficial physiological effect on the host by selectively stimulating the favorable growth or activity of a limited number of indigenous bacteria. Prebiotics function complementary to, and possibly synergistically with, probiotics. Numerous studies are providing insights into the growth and metabolic influence of these microbial nutrients on health. Today, the science behind the function of probiotics and prebiotics still requires more stringent deciphering both scientifically and mechanistically. The explosion of publications and interest in probiotics and prebiotics has resulted in a body of collective research that points toward great promise. However, this research is spread among such a diversity of organisms, delivery vehicles (foods, pills, and supplements), and potential health targets such that general conclusions cannot easily be made. Nevertheless, this situation is rapidly changing on a number of important fronts. With progress over the past decade on the genetics of lactic acid bacteria and the recent, 2,3 and pending, 4 release of complete genome sequences for major probiotic species, the field is now armed with detailed information and sophisticated microbiological and bioinformatic tools. Similarly, advances in biotechnology could yield new probiotics and prebiotics designed for enhanced or expanded functionality. The incorporation of genetic tools within a multidisciplinary scientific platform is expected to reveal the contributions of commensals, probiotics, and prebiotics to general health and well being and explicitly identify the mechanisms and corresponding host responses that provide the basis for their positive roles and associated claims. In terms of human suffering, the need for effective new approaches to prevent and treat disease is paramount. The need exists not only to alleviate the significant mortality and morbidity caused by intestinal diseases worldwide (especially diarrheal diseases in children), but also for infections at non-intestinal sites. This is especially worthy of pursuit in developing nations where mortality is too often the outcome of food and water borne infection. Inasmuch as probiotics and prebiotics are able to influence the populations or activities of commensal microflora, there is evidence that they can also play a role in mitigating some diseases. 5,6 Preliminary support that probiotics and prebiotics may be useful as intervention in conditions including inflammatory bowel disease, irritable bowel syndrome, allergy, cancer (especially colorectal cancer of which 75% are associated with diet), vaginal and urinary tract infections in women, kidney stone disease, mineral absorption, and infections caused by Helicobacter pylori is emerging. Some metabolites of microbes in the gut may also impact systemic conditions ranging from coronary heart disease to cognitive function, suggesting the possibility that exogenously applied microbes in the form of probiotics, or alteration of gut microecology with prebiotics, may be useful interventions even in these apparently disparate conditions. Beyond these direct intervention targets, probiotic cultures can also serve in expanded roles as live vehicles to deliver biologic agents (vaccines, enzymes, and proteins) to targeted locations within the body. The economic impact of these disease conditions in terms of diagnosis, treatment, doctor and hospital visits, and time off work exceeds several hundred billion dollars. The quality of life impact is also of major concern. Probiotics and prebiotics offer plausible opportunities to reduce the morbidity associated with these conditions. The following addresses issues that emerged from 8 workshops (Definitions, Intestinal Flora, Extra-Intestinal Sites, Immune Function, Intestinal Disease, Cancer, Genomics, and Second Generation Prebiotics), reflecting the current scientific state of probiotics and prebiotics. This is not a comprehensive review, however the study emphasizes pivotal knowledge gaps, and recommendations are made as to the underlying scientific and multidisciplinary studies that will be required to advance our understanding of the roles and impact of prebiotics, probiotics, and the commensal microflora upon health and disease management.