The gut microbiome as therapeutic target

被引:273
作者
Cani, Patrice D. [1 ]
Delzenne, Nathalie M. [1 ]
机构
[1] Catholic Univ Louvain, LDRI, Metab & Nutr Res Grp, B-1200 Brussels, Belgium
关键词
Gut microbiota; LPS; Obesity/type; 2; diabetes; Gut permeability; Inflammation; Endocannabinoid system; GLUCAGON-LIKE PEPTIDE-1; DIET-INDUCED OBESITY; HIGH-FAT-DIET; OLIGOFRUCTOSE PROMOTES SATIETY; ADIPOSE-TISSUE INFLAMMATION; RECEPTOR 2-DEFICIENT MICE; TOLL-LIKE RECEPTOR-4; INSULIN-RESISTANCE; WEIGHT-LOSS; ENDOCANNABINOID SYSTEM;
D O I
10.1016/j.pharmthera.2011.01.012
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Obesity, type-2 diabetes and low-grade inflammation are becoming worldwide epidemics. In this regard, the literature provides a novel concept that we call "MicrObesity" (Microbes and Obesity), which is devoted to deciphering the specific role of dysbiosis and its impact on host metabolism and energy storage. In the present review, we discuss novel findings that may partly explain how the microbial community participates in the development of the fat mass development, insulin resistance and low-grade inflammation that characterise obesity. In recent years, numerous mechanisms have been proposed and several proteins identified. Amongst the key players involved in the control of fat mass development. Fasting induced adipose factor, AMP-activated protein kinase, G-protein coupled receptor 41 and G-protein coupled receptor 43 have been linked to gut microbiota. In addition, the discovery that low-grade inflammation might be directly linked to the gut microbiota through metabolic endotoxaemia (elevated plasma lipopolysaccharide levels) has led to the identification of novel mechanisms involved in the control of the gut barrier. Amongst these, the impacts of glucagon-like peptide-2, the endocannabinoid system and specific bacteria (e.g., Bifidobacterium spp.) have been investigated. Moreover, the advent of probiotic and prebiotic treatments appears to be a promising "pharmaco-nutritional" approach to reversing the host metabolic alterations linked to the dysbiosis observed in obesity. Although novel powerful molecular system biology approaches have offered great insight into this "small world within", more studies are needed to unravel how specific changes in the gut microbial community might affect or counteract the development of obesity and related disorders. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:202 / 212
页数:11
相关论文
共 144 条
  • [1] ANTIBIOTICS PREVENT LIVER-INJURY IN RATS FOLLOWING LONG-TERM EXPOSURE TO ETHANOL
    ADACHI, Y
    MOORE, LE
    BRADFORD, BU
    GAO, WS
    THURMAN, RG
    [J]. GASTROENTEROLOGY, 1995, 108 (01) : 218 - 224
  • [2] Changes in endotoxin levels in T2DM subjects on anti-diabetic therapies
    Al-Attas, Omar S.
    Al-Daghri, Nasser M.
    Al-Rubeaan, Khalid
    da Silva, Nancy F.
    Sabico, Shaun L.
    Kumar, Sudhesh
    McTernan, Philip G.
    Harte, Alison L.
    [J]. CARDIOVASCULAR DIABETOLOGY, 2009, 8
  • [3] The metabolic syndrome - a new worldwide definition
    Alberti, KGMM
    Zimmet, P
    Shaw, J
    [J]. LANCET, 2005, 366 (9491) : 1059 - 1062
  • [4] Pharmacological Effects of Cannabinoids on the Caco-2 Cell Culture Model of Intestinal Permeability
    Alhamoruni, A.
    Lee, A. C.
    Wright, K. L.
    Larvin, M.
    O'Sullivan, S. E.
    [J]. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2010, 335 (01) : 92 - 102
  • [5] Energy intake is associated with endotoxemia in apparently healthy men
    Amar, Jacques
    Burcelin, Remy
    Ruidavets, Jean Bernard
    Cani, Patrice D.
    Fauvel, Josette
    Alessi, Marie Christine
    Chamontin, Bernard
    Ferrieres, Jean
    [J]. AMERICAN JOURNAL OF CLINICAL NUTRITION, 2008, 87 (05) : 1219 - 1223
  • [6] Innate immunity modulates adipokines in humans
    Anderson, Paul D.
    Mehta, Nehal N.
    Wolfe, Megan L.
    Hinkle, Christine C.
    Pruscino, Leticia
    Comiskey, Lynne L.
    Tabita-Martinez, Jennifer
    Sellers, Kimberly F.
    Rickels, Michael R.
    Ahima, Rexford S.
    Reilly, Muredach P.
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2007, 92 (06) : 2272 - 2279
  • [7] ANDREASEN AS, 2010, BR J NUTR, P1
  • [8] Effect of fat replacement by inulin or lupin-kernel fibre on sausage patty acceptability, post-meal perceptions of satiety and food intake in ment
    Archer, BJ
    Johnson, SK
    Devereux, HM
    Baxter, AL
    [J]. BRITISH JOURNAL OF NUTRITION, 2004, 91 (04) : 591 - 599
  • [9] Monitoring Bacterial Community of Human Gut Microbiota Reveals an Increase in Lactobacillus in Obese Patients and Methanogens in Anorexic Patients
    Armougom, Fabrice
    Henry, Mireille
    Vialettes, Bernard
    Raccah, Denis
    Raoult, Didier
    [J]. PLOS ONE, 2009, 4 (09):
  • [10] Decreased Fat Storage by Lactobacillus Paracasei Is Associated with Increased Levels of Angiopoietin-Like 4 Protein (ANGPTL4)
    Aronsson, Linda
    Huang, Ying
    Parini, Paolo
    Korach-Andre, Marion
    Hakansson, Janet
    Gustafsson, Jan-Ake
    Pettersson, Sven
    Arulampalam, Velmurugesan
    Rafter, Joseph
    [J]. PLOS ONE, 2010, 5 (09): : 1 - 7