title: Persistent microbiome alterations modulate the rate of post-dieting weight regain.
abstract: 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.
authors.affiliation: Immunology Department, Weizmann Institute of Science, 76100 Rehovot, Israel.
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Thaiss
authors.affiliation: Immunology Department, Weizmann Institute of Science, 76100 Rehovot, Israel.
authors.forename: Shlomik
authors.initials: S
authors.lastname: Itav
authors.affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, 76100 Rehovot, Israel.|Department of Molecular Cell Biology, Weizmann Institute of Science, 76100 Rehovot, Israel.
authors.forename: Daphna
authors.initials: D
authors.lastname: Rothschild
authors.affiliation: Immunology Department, Weizmann Institute of Science, 76100 Rehovot, Israel.
authors.forename: Mariska T
authors.initials: MT
authors.lastname: Meijer
authors.affiliation: Immunology Department, Weizmann Institute of Science, 76100 Rehovot, Israel.
authors.forename: Maayan
authors.initials: M
authors.lastname: Levy
authors.affiliation: Immunology Department, Weizmann Institute of Science, 76100 Rehovot, Israel.
authors.forename: Claudia
authors.initials: C
authors.lastname: Moresi
authors.affiliation: Immunology Department, Weizmann Institute of Science, 76100 Rehovot, Israel.
authors.forename: Lenka
authors.initials: L
authors.lastname: Dohnalová
authors.affiliation: Immunology Department, Weizmann Institute of Science, 76100 Rehovot, Israel.
authors.forename: Sofia
authors.initials: S
authors.lastname: Braverman
authors.affiliation: Immunology Department, Weizmann Institute of Science, 76100 Rehovot, Israel.
authors.forename: Shachar
authors.initials: S
authors.lastname: Rozin
authors.affiliation: Department of Plant and Environmental Sciences, Weizmann Institute of Science, 76100 Rehovot, Israel.
authors.forename: Sergey
authors.initials: S
authors.lastname: Malitsky
authors.affiliation: Immunology Department, Weizmann Institute of Science, 76100 Rehovot, Israel.
authors.forename: Mally
authors.initials: M
authors.lastname: Dori-Bachash
authors.affiliation: Department of Veterinary Resources, Weizmann Institute of Science, 76100 Rehovot, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Kuperman
authors.affiliation: Department of Veterinary Resources, Weizmann Institute of Science, 76100 Rehovot, Israel.
authors.forename: Inbal
authors.initials: I
authors.lastname: Biton
authors.affiliation: The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University, Rehovot 76100, Israel.
authors.forename: Arieh
authors.initials: A
authors.lastname: Gertler
authors.affiliation: Department of Veterinary Resources, Weizmann Institute of Science, 76100 Rehovot, Israel.
authors.forename: Alon
authors.initials: A
authors.lastname: Harmelin
authors.affiliation: Immunology Department, Weizmann Institute of Science, 76100 Rehovot, Israel.
authors.forename: Hagit
authors.initials: H
authors.lastname: Shapiro
authors.affiliation: Research Center for Digestive Tract and Liver Diseases, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, 69978 Tel Aviv, Israel.|Digestive Center, Tel Aviv Sourasky Medical Center, 64239 Tel Aviv, Israel.
authors.forename: Zamir
authors.initials: Z
authors.lastname: Halpern
authors.affiliation: Department of Plant and Environmental Sciences, Weizmann Institute of Science, 76100 Rehovot, Israel.
authors.forename: Asaph
authors.initials: A
authors.lastname: Aharoni
authors.affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, 76100 Rehovot, Israel.|Department of Molecular Cell Biology, Weizmann Institute of Science, 76100 Rehovot, Israel.
authors.forename: Eran
authors.initials: E
authors.lastname: Segal
authors.affiliation: Immunology Department, Weizmann Institute of Science, 76100 Rehovot, Israel.
authors.forename: Eran
authors.initials: E
authors.lastname: Elinav