Prebiotic supplementation of In Vitro fecal fermentations inhibits proteolysis by gut bacteria, and host diet shapes gut bacterial metabolism and response to intervention

Metabolism of protein by gut bacteria is potentially detrimental due to the production of toxic metabolites, such as ammonia, amines, p-cresol, and indole. The consumption of prebiotic carbohydrates results in specific changes in the composition and/or activity of the microbiota that may confer benefits to host well-being and health. Here, we have studied the impact of prebiotics on proteolysis within the gut in vitro. Anaerobic stirred batch cultures were inoculated with feces from omnivores (n = 3) and vegetarians (n = 3) and four protein sources (casein, meat, mycoprotein, and soy protein) with and without supplementation by an oligofructose-enriched inulin. Bacterial counts and concentrations of short-chain fatty acids (SCFA), ammonia, phenol, indole, and p-cresol were monitored during fermentation. Addition of the fructan prebiotic Synergy1 increased levels of bifidobacteria (P = 0.000019 and 0.000013 for omnivores and vegetarians, respectively). Branched-chain fatty acids (BCFA) were significantly lower in fermenters with vegetarians’ feces (P = 0.004), reduced further by prebiotic treatment. Ammonia production was lower with Synergy1. Bacterial adaptation to different dietary protein sources was observed through different patterns of ammonia production between vegetarians and omnivores. In volunteer samples with high baseline levels of phenol, indole, p-cresol, and skatole, Synergy1 fermentation led to a reduction of these compounds

Exploring the genetic aetiology of trust in adolescents:Combined twin and DNA analyses

Behavioral traits generally show moderate to strong genetic influence, with heritability estimates of around 50%. Some recent research has suggested that trust may be an exception because it is more strongly influenced by social interactions. In a sample of over 7,000 adolescent twins from the United Kingdom’s Twins Early Development Study, we found broad sense heritability estimates of 57% for generalized trust and 51% for trust in friends. Genomic-relatedness-matrix restricted maximum likelihood (GREML) estimates in the same sample indicate that 21% of the narrow sense genetic variance can be explained by common single nucleotide polymorphisms for generalized trust and 43% for trust in friends. As expected, this implies a large amount of unexplained heritability, although power is low for estimating DNA-based heritability. The missing heritability may be accounted for by interactions between DNA and the social environment during development or via gene–environment correlations with rare variants. How these genes and environments correlate seem especially important for the development of trust

A polygenic approach to understanding resilience to peer victimisation

Previous studies suggest an individual’s risk of depression following adversity may be moderated by their genetic liability. No study, however, has examined peer victimisation, an experience repeatedly associated with mental illness. We explore whether the negative mental health outcomes following victimisation can be partly attributed to genetic factors using polygenic scores for depression and wellbeing. Among participants from the Avon Longitudinal Study of Parents and Children (ALSPAC), we show that polygenic scores and peer victimisation are significant independent predictors of depressive symptoms (n=2268) and wellbeing (n=2299) in early adulthood. When testing for interaction effects, our results lead us to conclude that low mental health and wellbeing following peer victimisation is unlikely to be explained by a moderating effect of genetic factors, as indexed by current polygenic scores. Genetic profiling is therefore unlikely to be effective in identifying those more vulnerable to the effects of victimisation at present. The reasons why some go on to experience mental health problems following victimisation, while others remain resilient, requires further exploration, but our results rule out a major influence of current polygenic scores

Positive wellbeing and resilience following adolescent victimisation: An exploration into protective factors across development

Background Not all victims of bullying go on to develop problems with their mental health. To understand factors that may confer resilience, many have explored the moderating role of protective factors in relation to mental illness. No study to date, however, has considered moderators of adult wellbeing following victimisation. We explore 14 protective factors and test whether these promote good adult wellbeing in addition to prevent mental illness following victimisation. In doing so, we aimed to understand how positive mental health and resilience can be promoted. Methods Data were derived from the Avon Longitudinal Study of Parents and Children. Participants were assessed for wellbeing and depressive symptoms at age 23, as well as victimisation in adolescence, and protective factors across development. Protective factors were categorised into individual-, family- and peer-level, and included factors like social skills, perceived school competence, and relationships with family and peers. The moderating role of the protective factors were examined using interactive regression models. Results Perceived scholastic competence was the only factor that mitigated some of the negative effects of victimisation. Individuals with higher perceptions of scholastic competence had higher wellbeing in adulthood than victims with lower perceptions of competence. No protective factors positively moderated life satisfaction or the risk of depressive symptoms; although findings suggest that friendships in late adolescence may be protective for individuals exposed to less frequent victimisation. Conclusions Our study is the first to explore a wide range of protective factors in predicting adult wellbeing following victimisation. We identify factors involved specifically in supporting wellbeing but not in reducing the risk of depression. Findings suggest that interventions aimed at increasing perceptions of scholastic competence in childhood may help to support more positive wellbeing in adulthood

Peer victimisation during adolescence and its impact on wellbeing in adulthood: a prospective cohort study

Background Peer victimisation is a common occurrence and has well-established links with a range of psychiatric problems in adulthood. Significantly less is known however, about how victimisation influences positive aspects of mental health such as wellbeing. The purpose of this study was therefore to assess for the first time, whether peer victimisation in adolescence is associated with adult wellbeing. We aimed to understand whether individuals who avoid a diagnosis of depression after victimisation, maintain good wellbeing in later life, and therefore display resilience. Methods Longitudinal data was taken from the Avon Longitudinal Study of Parents and Children, a prospective cohort study based in the UK. Peer victimisation was assessed at 13 years using a modified version of the bullying and friendship interview schedule, and wellbeing at age 23 using the Warwick-Edinburgh Mental Well-Being Scale. The presence or absence of depression was diagnosed using the Clinical Interview Schedule–Revised at 18 years. A series of logistic and linear regression analyses were used to explore relationships between peer victimisation, depression, and wellbeing, adjusting for potentially confounding individual and family factors. Results Just over 15% of victims of frequent bullying had a diagnosis of depression at age 18. Victimisation also had a significant impact on wellbeing, with a one-point increase in frequent victimisation associated with a 2.71-point (SE = 0.46, p < 0.001) decrease in wellbeing scores aged 23. This finding remained after adjustment for the mediating and moderating effects of depression, suggesting that the burden of victimisation extends beyond depression to impact wellbeing. Results therefore show that individuals who remain partially resilient by avoiding a diagnosis of depression after victimisation have significantly poorer wellbeing than their non-victimised counterparts. Conclusion Overall, our study demonstrates for the first time that victimisation during adolescence is a significant risk factor for not only the onset of depression, but also poor wellbeing in adulthood. Such findings highlight the importance of investigating both dimensions of mental health to understand the true burden of victimisation and subsequent resilience. In addition to the need for interventions that reduce the likelihood of depression following adolescent victimisation, efforts should also be made to promote good wellbeing

A Gene Expression Signature of Invasive Potential in Metastatic Melanoma Cells

BACKGROUND: We are investigating the molecular basis of melanoma by defining genomic characteristics that correlate with tumour phenotype in a novel panel of metastatic melanoma cell lines. The aim of this study is to identify new prognostic markers and therapeutic targets that might aid clinical cancer diagnosis and management. PRINCIPAL FINDINGS: Global transcript profiling identified a signature featuring decreased expression of developmental and lineage specification genes including MITF, EDNRB, DCT, and TYR, and increased expression of genes involved in interaction with the extracellular environment, such as PLAUR, VCAN, and HIF1a. Migration assays showed that the gene signature correlated with the invasive potential of the cell lines, and external validation by using publicly available data indicated that tumours with the invasive gene signature were less melanocytic and may be more aggressive. The invasion signature could be detected in both primary and metastatic tumours suggesting that gene expression conferring increased invasive potential in melanoma may occur independently of tumour stage. CONCLUSIONS: Our data supports the hypothesis that differential developmental gene expression may drive invasive potential in metastatic melanoma, and that melanoma heterogeneity may be explained by the differing capacity of melanoma cells to both withstand decreased expression of lineage specification genes and to respond to the tumour microenvironment. The invasion signature may provide new possibilities for predicting which primary tumours are more likely to metastasize, and which metastatic tumours might show a more aggressive clinical course