Links between host genetics, metabolism, gut microbiome and amoebic gill disease (AGD) in Atlantic Salmon

Background: Rapidly spreading parasitic infections like amoebic gill disease (AGD) are increasingly problematic for Atlantic salmon reared in aquaculture facilities and potentially pose a risk to wild fish species in surrounding waters. Currently, it is not known whether susceptibility to AGD differs between wild and farmed salmon. Wild Atlantic salmon populations are declining and this emerging disease could represent an additional threat to their long-term viability. A better understanding of how AGD affects fish health is therefore relevant for the accurate assessment of the associated risk, both to farming and to the well-being of wild populations. In this study, we assessed the impact of natural exposure to AGD on wild, hybrid and farmed post-smolt Atlantic salmon reared in a sea farm together under common garden conditions. Results: Wild fish showed substantially higher mortality levels (64%) than farmed fish (25%), with intermediate levels for hybrid fish (39%) suggesting that AGD susceptibility has an additive genetic basis. Metabolic rate measures representing physiological performance were similar among the genetic groups but were significantly lower in AGD-symptomatic fish than healthy fish. Gut microbial diversity was significantly lower in infected fish. We observed major shifts in gut microbial community composition in response to AGD infections. In symptomatic fish the relative abundance of key taxa Aliivibrio, Marinomonas and Pseudoalteromonas declined, whereas the abundance of Polaribacter and Vibrio increased compared to healthy fish. Conclusions: Our results highlight the stress AGD imposes on fish physiology and suggest that low metabolic-rate fish phenotypes may be associated with better infection outcomes. We consider the role increased AGD outbreak events and a warmer future may have in driving secondary bacterial infections and in reducing performance in farmed and wild fish

RESCALE: Review and Simulate Climate and Catchment Responses at Burrishoole : Marine Research Sub-Programme (NDP 2007-’13) Series. ISSN 2009-3195

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New metrics for the Lancet Standing Commission on Liver Disease in the UK

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A randomised controlled trial of extended brief intervention for alcohol dependent patients in an acute hospital setting (ADPAC)

<p>Abstract</p> <p>Background</p> <p>Alcohol dependence affects approximately 3% of the English population, and accounts for significant medical and psychiatric morbidity. Only 5.6% of alcohol-dependent individuals ever access specialist treatment and only a small percentage ever seek treatment. As people who are alcohol dependent are more likely to have experienced health problems leading to frequent attendance at acute hospitals it would seem both sensible and practical to ensure that this setting is utilised as a major access point for treatment, and to test the effectiveness of these treatments.</p> <p>Methods/Design</p> <p>This is a randomised controlled trial with a primary hypothesis that extended brief interventions (EBI) delivered to alcohol-dependent patients in a hospital setting by an Alcohol Specialist Nurse (ASN) will be effective when compared to usual care in reducing overall alcohol consumption and improving on the standard measures of alcohol dependence. Consecutive patients will be screened for alcohol misuse in the Emergency Department (ED) of a district general hospital. On identification of an alcohol-related problem, following informed written consent, we aim to randomize 130 patients per group. The ASN will discharge to usual clinical care all control group patients, and plan a programme of EBI for treatment group patients. Follow-up interview will be undertaken by a researcher blinded to the intervention at 12 and 24 weeks. The primary outcome measure is level of alcohol dependence as determined by the Severity of Alcohol Dependence Questionnaire (SADQ) score. Secondary outcome measures include; Alcohol Use Disorders Identification Test (AUDIT) score, quantity and frequency of alcohol consumption, health-related quality of life measures, service utilisation, and patient experience. The trial will also allow an assessment of the cost-effectiveness of EBI in an acute hospital setting. In addition, patient experience will be assessed using qualitative methods.</p> <p>Discussion</p> <p>This paper presents a protocol for a RCT of EBI delivered to alcohol dependent patients by an ASN within an ED. Importantly; the trial will also seek to understand patients' perceptions and experiences of being part of a RCT and of receiving this form of intervention.</p> <p>Trial registration number</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN78062794">ISRCTN78062794</a></p

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Additional file 1 of Links between host genetics, metabolism, gut microbiome and amoebic gill disease (AGD) in Atlantic salmon

Additional file 1: Table S1. Overview of the metabolic rate experiment. Sample_Id refers to individual fish. Sampling day refers to the day when fish were caught. Processing day refers to the day fish were dissected. Experiment day equals processing days, only in another format. Temperature refers to the water temperature at the sea pens on each sampling day. Table S2. First round PCR primers used for NGS library preparation. Table S3. Second round PCR primers used for NGS library preparation. Table S4. Mean length, weight and Fulton’s condition factor per genetic origin for 3 points in time (pre sea pen hatchery, date of sea pen transfer and at the termination point of the experiment). Table S5. ANCOVA results of the effect of AGD severity Score on weight adjusted SMR (left), MMR (middle) and AS (right) measures. Significance codes: *** < 0.001; ** < 0.01; * < 0.05. Table S6. Multiple comparisons of means of metabolic rate measures between different AGD severity scores (Tukey post-hoc for weight-adjusted model). Significance codes: ** < 0.01; * < 0.05. Table S7. Permanova results showing differences between gut microbial community compositions of starved and fed fish for two different timepoints T0 and T1 in PC samples. Significance codes: ** < 0.01; * < 0.05. Table S8. Permanova results showing differences between gut microbial community compositions of starved and fed fish for two different timepoints T0 and T1 in MG samples. Significance codes: ** < 0.01; * < 0.05. Table S9. Linear model for Chao1 richness estimates in MG samples calculated by the interaction term of AGD severity score and genetic origin. AGD severity of 0 and farmed origin served as baseline for comparisons. Significance codes: *** < 0.001; ** < 0.01; * < 0.05. Table S10. Permutational analysis of variance (PERMANOVA) results testing the effect of AGD severity score, genetic origin and processing day (day of gut dissection) on pyloric caeca (PC) microbial community composition based on weighted unifrac distance matrices. Table S11. Permanova of pairwise comparisons of PC samples grouped by day of their processing. Distance matrix calculated by weighted UniFrac measure. Permutations used: 9999. Significance codes: *** < 0.001; ** < 0.01; * < 0.05. Table S12. Permutational analysis of variance (PERMANOVA) results testing the effect of AGD severity score, genetic origin and processing day (day of gut dissection) on midgut (MG) microbial community composition based on weighted unifrac distance matrices. Table S13. Permutational analysis of variance (PERMANOVA) testing pairwise comparisons for midgut (MG) samples from different AGD severity groups. Distance matrix calculated by weighted UniFrac measure. Permutations used: 9999. Significance codes: **p < 0.01; *p < 0.05