Anatole Ghazalpour1, Ivana Cespedes, Brian J Bennett, Hooman Allayee. 1. aDepartment of Human Genetics, David Geffen School of Medicine of UCLA bDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California cInstitute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California dDepartments of Genetics eNutrition fNutrition Research Institute, University of North Carolina, Chapel Hill, North Carolina, USA.
Abstract
PURPOSE OF REVIEW: This article highlights recent advances in the emerging role that gut microbiota play in modulating metabolic phenotypes, with a particular focus on lipid metabolism. RECENT FINDINGS: Accumulating data from both human and animal studies demonstrate that intestinal microbes can affect host lipid metabolism through multiple direct and indirect biological mechanisms. These include a variety of signaling molecules produced by gut bacteria that have potent effects on hepatic lipid and bile metabolism and on reverse cholesterol transport, energy expenditure, and insulin sensitivity in peripheral tissues. Additionally, host genetic factors can modulate the abundance of bacterial taxa, which can subsequently affect various metabolic phenotypes. Proof of causality for identified microbial associations with host lipid-related phenotypes has been demonstrated in several animal studies, but remains a challenge in humans. Ultimately, selective manipulation of the gut microbial ecosystem for intervention will first require a better understanding of which specific bacteria, or alternatively, which bacterial metabolites, are appropriate targets. SUMMARY: Recent discoveries have broad implications for elucidating bacterially mediated pathophysiological mechanisms that alter lipid metabolism and other related metabolic traits. From a clinical perspective, this newly recognized endocrine organ system can be targeted for therapeutic benefit of dyslipidemia and cardiometabolic diseases.
PURPOSE OF REVIEW: This article highlights recent advances in the emerging role that gut microbiota play in modulating metabolic phenotypes, with a particular focus on lipid metabolism. RECENT FINDINGS: Accumulating data from both human and animal studies demonstrate that intestinal microbes can affect host lipid metabolism through multiple direct and indirect biological mechanisms. These include a variety of signaling molecules produced by gut bacteria that have potent effects on hepatic lipid and bile metabolism and on reverse cholesterol transport, energy expenditure, and insulin sensitivity in peripheral tissues. Additionally, host genetic factors can modulate the abundance of bacterial taxa, which can subsequently affect various metabolic phenotypes. Proof of causality for identified microbial associations with host lipid-related phenotypes has been demonstrated in several animal studies, but remains a challenge in humans. Ultimately, selective manipulation of the gut microbial ecosystem for intervention will first require a better understanding of which specific bacteria, or alternatively, which bacterial metabolites, are appropriate targets. SUMMARY: Recent discoveries have broad implications for elucidating bacterially mediated pathophysiological mechanisms that alter lipid metabolism and other related metabolic traits. From a clinical perspective, this newly recognized endocrine organ system can be targeted for therapeutic benefit of dyslipidemia and cardiometabolic diseases.
Authors: Marc-Emmanuel Dumas; Richard H Barton; Ayo Toye; Olivier Cloarec; Christine Blancher; Alice Rothwell; Jane Fearnside; Roger Tatoud; Véronique Blanc; John C Lindon; Steve C Mitchell; Elaine Holmes; Mark I McCarthy; James Scott; Dominique Gauguier; Jeremy K Nicholson Journal: Proc Natl Acad Sci U S A Date: 2006-08-08 Impact factor: 11.205
Authors: Jaana Hartiala; Brian J Bennett; W H Wilson Tang; Zeneng Wang; Alexandre F R Stewart; Robert Roberts; Ruth McPherson; Aldons J Lusis; Stanley L Hazen; Hooman Allayee Journal: Arterioscler Thromb Vasc Biol Date: 2014-03-27 Impact factor: 8.311
Authors: Jill C Gregory; Jennifer A Buffa; Elin Org; Zeneng Wang; Bruce S Levison; Weifei Zhu; Matthew A Wagner; Brian J Bennett; Lin Li; Joseph A DiDonato; Aldons J Lusis; Stanley L Hazen Journal: J Biol Chem Date: 2014-12-30 Impact factor: 5.157
Authors: Diana M Shih; Zeneng Wang; Richard Lee; Yonghong Meng; Nam Che; Sarada Charugundla; Hannah Qi; Judy Wu; Calvin Pan; J Mark Brown; Thomas Vallim; Brian J Bennett; Mark Graham; Stanley L Hazen; Aldons J Lusis Journal: J Lipid Res Date: 2014-11-06 Impact factor: 5.922
Authors: Fredrik Bäckhed; Hao Ding; Ting Wang; Lora V Hooper; Gou Young Koh; Andras Nagy; Clay F Semenkovich; Jeffrey I Gordon Journal: Proc Natl Acad Sci U S A Date: 2004-10-25 Impact factor: 11.205
Authors: Julia K Goodrich; Jillian L Waters; Angela C Poole; Jessica L Sutter; Omry Koren; Ran Blekhman; Michelle Beaumont; William Van Treuren; Rob Knight; Jordana T Bell; Timothy D Spector; Andrew G Clark; Ruth E Ley Journal: Cell Date: 2014-11-06 Impact factor: 41.582
Authors: Gary D Wu; Jun Chen; Christian Hoffmann; Kyle Bittinger; Ying-Yu Chen; Sue A Keilbaugh; Meenakshi Bewtra; Dan Knights; William A Walters; Rob Knight; Rohini Sinha; Erin Gilroy; Kernika Gupta; Robert Baldassano; Lisa Nessel; Hongzhe Li; Frederic D Bushman; James D Lewis Journal: Science Date: 2011-09-01 Impact factor: 47.728
Authors: Jorge Henao-Mejia; Eran Elinav; Chengcheng Jin; Liming Hao; Wajahat Z Mehal; Till Strowig; Christoph A Thaiss; Andrew L Kau; Stephanie C Eisenbarth; Michael J Jurczak; Joao-Paulo Camporez; Gerald I Shulman; Jeffrey I Gordon; Hal M Hoffman; Richard A Flavell Journal: Nature Date: 2012-02-01 Impact factor: 49.962
Authors: Paolo Marzullo; Laura Di Renzo; Gabriella Pugliese; Martina De Siena; Luigi Barrea; Giovanna Muscogiuri; Annamaria Colao; Silvia Savastano Journal: Int J Obes Suppl Date: 2020-07-20
Authors: Aaro Salosensaari; Ville Laitinen; Leo Lahti; Teemu Niiranen; Aki S Havulinna; Guillaume Meric; Susan Cheng; Markus Perola; Liisa Valsta; Georg Alfthan; Michael Inouye; Jeramie D Watrous; Tao Long; Rodolfo A Salido; Karenina Sanders; Caitriona Brennan; Gregory C Humphrey; Jon G Sanders; Mohit Jain; Pekka Jousilahti; Veikko Salomaa; Rob Knight Journal: Nat Commun Date: 2021-05-11 Impact factor: 14.919
Authors: Maria Luisa Matey-Hernandez; Frances M K Williams; Tilly Potter; Ana M Valdes; Tim D Spector; Cristina Menni Journal: Physiol Genomics Date: 2017-12-20 Impact factor: 3.107