Journal
NATURE
Volume 540, Issue 7634, Pages 544-+Publisher
NATURE RESEARCH
DOI: 10.1038/nature20796
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Funding
- Boehringer Ingelheim Fonds PhD Fellowship
- Levi Eshkol PhD Scholarship for Personalized Medicine by the Israeli Ministry of Science
- Crown Human Genome Center
- Else Kroener Fresenius Foundation
- European Research Council
- National Institute of Health
- Israel Science Foundation
- Frenkel Foundation for the Promotion of Life Sciences
- Gurwin Family Fund for Scientific Research
- Leona M. and Harry B. Helmsley Charitable Trust
- Crown Endowment Fund for Immunological Research
- Benoziyo Endowment Fund for the Advancement of Science
- Adelis Foundation
- French National Center for Scientific Research (CNRS)
- Marie Curie Integration grant
- German-Israeli Foundation for Scientific Research and Development
- Minerva Foundation
- Rising Tide Foundation
- Helmholtz Foundation
- European Foundation for the Study of Diabetes
- European Foundation for the Study of Diabetes [Lilly 2015_7] Funding Source: researchfish
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In tackling the obesity pandemic, considerable efforts are devoted to the development of effective weight reduction strategies, yet many dieting individuals fail to maintain a long-term weight reduction, and instead undergo excessive weight regain cycles. The mechanisms driving recurrent post-dieting obesity remain largely elusive. Here we identify an intestinal microbiome signature that persists after successful dieting of obese mice and contributes to faster weight regain and metabolic aberrations upon re-exposure to obesity-promoting conditions. Faecal transfer experiments show that the accelerated weight regain phenotype can be transmitted to germ-free mice. We develop a machine-learning algorithm that enables personalized microbiome-based prediction of the extent of post-dieting weight regain. Additionally, we find that the microbiome contributes to diminished post-dieting flavonoid levels and reduced energy expenditure, and demonstrate that flavonoid-based 'post-biotic' intervention ameliorates excessive secondary weight gain. Together, our data highlight a possible microbiome contribution to accelerated post-dieting weight regain, and suggest that microbiome-targeting approaches may help to diagnose and treat this common disorder.
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