Disrupted intestinal microbiota contributes to the pathogenesis of anorexia nervosa
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ABSTRACT:
PROVIDER: PRJEB51776 | ENA |
REPOSITORIES: ENA
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Project description:Anorexia nervosa (AN) is an eating disorder with a high mortality affecting about 1% of women, where no evidence-based effective treatment exists. The pathogenesis likely involves genetic and environmental alterations. We hypothesized that a disrupted gut microbiota contributes to AN pathogenesis. In analyses comparing 70 AN with 77 healthy females, we found multiple taxa, functional modules, structural variants and growth rates of bacterial gut microbiota, and viral gut microbiota that were altered in AN with parts of these perturbations linked to estimates of eating behavior and mental health. In silico, causal inference analyses implied serum bacterial metabolites mediated parts of the impact of altered gut microbiota on AN behavior, and in vivo, three independent fecal microbiota transplantation from AN cases to germ-free mice under energy restricted feeding mirroring AN eating behavior consistently induced a lower body weight gain and hypothalamic and adipose tissue gene expressions related to aberrant energy metabolism and eating and mental behavior.
2022-05-18 | ST002494 | MetabolomicsWorkbench
Project description:Anorexia nervosa (AN) is an eating disorder with a high mortality affecting about 0.5% of women, where no evidence-based effective treatment exists. The pathogenesis likely involves genetic and environmental alterations. We hypothesized that a disrupted gut microbiota contributes to AN pathology. In analyses comparing 70 AN with 77 healthy females, we found multiple taxa, functional modules, structural variants and growth rates of bacterial gut microbiota, and viral gut microbiota that were altered in AN with parts of these perturbations linked to estimates of eating behavior and mental health. In silico, causal inference analyses implied bacterial metabolites mediated parts of the impact of altered gut microbiota on AN behavior, and in vivo, fecal microbiota transplantation from AN cases to germ-free mice induced a lower body weight and hypothalamic and adipose tissue gene expressions related to aberrant energy metabolism and eating and mental behavior.
2022-05-18 | ST002495 | MetabolomicsWorkbench
Project description:Anorexia Nervosa Genetics Initiative (ANGI)
| PRJNA434031 | ENA
Project description:Anorexia Nervosa Genetics Initiative (ANGI)
| PRJNA434032 | ENA
Project description:As part of the Genetic Consortium for Anorexia Nervosa (GCAN) and Wellcome Trust Case
Control Consortium 3 (WTCCC3), we have amassed the largest anorexia nervosa (AN)
sample in the world (~4,000). Following the WTCCC3 GWAS, we secured funding from the
Klarman Family Foundation to extend the genetic analyses to variants on the exome chip
(CoreExome array). This pre-lim relates to carrying out genotyping on the CoreExome array
on up to a maximum of 580 new samples.
| EGAS00001000913 | EGA
Project description:VNN1 : a new biomarker of anorexia nervosa
| PRJNA1030915 | ENA
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.
2023-08-23 | GSE229316 | GEO
Project description:The role of gut microbiota in anorexia nervosa
| PRJEB38930 | ENA
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.
2023-10-31 | GSE245978 | GEO
Project description:Identification of adipose tissue metabolic memory of anorexia nervosa
| PRJNA954004 | ENA