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Skin microbiota analysis in patients with anorexia nervosa and healthy-weight controls reveals microbial indicators of healthy weight and associations with the antimicrobial peptide psoriasin

ABSTRACT: Skin microbiota analysis in patients with anorexia nervosa and healthy-weight controls

PROVIDER: PRJEB47175 | ENA |

REPOSITORIES: ENA

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Anorexia Nervosa Genetics Initiative (ANGI)

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Skin microbiota analysis in patients with anorexia nervosa and healthy-weight controls reveals microbial indicators of healthy weight and associations with the antimicrobial peptide psoriasin.

Project description:Anorexia nervosa (AN), a psychiatric condition defined by low body weight for age and height, is associated with numerous dermatological conditions. Yet, clinical observations report that patients with AN do not suffer from infectious skin diseases like those associated with primary malnutrition. Cell-mediated immunity appears to be amplified in AN; however, this proinflammatory state does not sufficiently explain the lower incidence of infections. Antimicrobial peptides (AMPs) are important components of the innate immune system protecting from pathogens and shaping the microbiota. In Drosophila melanogaster starvation precedes increased AMP gene expression. Here, we analyzed skin microbiota in patients with AN and age-matched, healthy-weight controls and investigated the influence of weight gain on microbial community structure. We then correlated features of the skin microbial community with psoriasin and RNase 7, two highly abundant AMPs in human skin, to clarify whether an association between AMPs and skin microbiota exists and whether such a relationship might contribute to the resistance to cutaneous infections observed in AN. We find significant statistical correlations between Shannon diversity and the highly abundant skin AMP psoriasin and bacterial load, respectively. Moreover, we reveal psoriasin significantly associates with Abiotrophia, an indicator for the healthy-weight control group. Additionally, we observe a significant correlation between an individual's body mass index and Lactobacillus, a microbial indicator of health. Future investigation may help clarify physiological mechanisms that link nutritional intake with skin physiology.

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VNN1 : a new biomarker of anorexia nervosa

Project description:VNN1 : a new biomarker of anorexia nervosa

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Project description:Anorexia nervosa (AN) is a complex debilitating disease characterized by intense fear of weight gain and excessive exercise. It is the deadliest of any psychiatric disorder with a high rate of recidivism, yet its pathophysiology is unclear. The Activity-Based Anorexia (ABA) paradigm is a widely accepted mouse model of AN that recapitulates hypophagia and hyperactivity despite reduced body weight, however, not the chronicity. Here, we modified the prototypical ABA paradigm to increase the time to lose 25% of baseline body weight from less than 7 days to more than 2 weeks. We used this paradigm to identify persistently altered genes after weight restoration that represent a metabolic memory of under-nutrition and may contribute to AN relapse. We focused on adipose tissue as it was identified as a major location of metabolic memory of over-nutririon. We identified 300 persistently dysregulated genes, including Calm2 and Vps13d, which could be potential global regulators of metabolic memory in both chronic over- and under-nutrition. However, despite being on the opposite spectrum of weight perturbations, the majority of metabolic memory genes of under- and over-nutrition do not overlap, suggestive of the different mechanisms involved in these extreme nutritional statuses.

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Project description:Anorexia nervosa (AN) is a psychiatric disorder with an estimated heritability of around 70%. Although the largest genome-wide association study meta-analysis on AN identified independent loci-conferring risk to the disorder, the molecular mechanisms underlying the genetic basis of AN remains to be elucidated. To explore AN, we ran a transcriptome profiling in peripheral blood mononuclear cells of 15 AN subjects and 15 healthy controls. We validated our mean results in a mouse model of chronic food restriction mimicking several aspects of AN. Through this exploratory study we identified 673 significantly differentially expressed genes in AN. Among these genes, we identified the Vanin-1 (Vnn1) gene that appears to play a major role in the regulation of multiple metabolic pathways. We confirmed an underexpression of Vnn1, especially in the liver, in a mouse model of chronic food restriction. These results indicate that quantitative food restriction affects Vnn1 expression, suggesting that this gene may contribute to the anorexic phenotype in the chronic food restriction mouse model as well as in patients affected by AN. We believe that this report highlights promising candidate genes and gene pathways for AN and reveals Vnn1 as a biomarker that may be used as molecular targets to predict and/or to understand AN.

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