Gut microbiota as a regulator of energy homeostasis and ectopic fat deposition: mechanisms and implications for metabolic disorders

被引:149
作者
Musso, Giovanni [1 ]
Gambino, Roberto [2 ]
Cassader, Maurizio [2 ]
机构
[1] Gradenigo Hosp, I-10132 Turin, Italy
[2] Univ Turin, Dept Internal Med, I-10124 Turin, Italy
关键词
endotoxin; energy homeostasis; microbiota; NAFLD; obesity; DIET-INDUCED OBESITY; NONALCOHOLIC STEATOHEPATITIS; LIVER-DISEASE; HEPATIC STEATOSIS; GLUCOSE-TOLERANCE; LINOLEIC-ACID; MICE; ENDOTOXEMIA; PATHOGENESIS; BIFIDOBACTERIA;
D O I
10.1097/MOL.0b013e3283347ebb
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Purpose of review To examine the role of gut microbiota in the regulation of host energy homeostasis and its role in the pathogenesis of obesity, diabetes and nonalcoholic fatty liver disease (NAFLD) Recent findings Experimental models highlight several mechanisms connecting gut microbiota to host energy metabolism: increased energy harvesting from the diet, regulation of appetite through gut peptide, secretion, regulation of tissue-free fatty acid composition and uptake, storage and oxidation, modulation of intestinal barrier by glucagon-like peptide-2 secretion, activation of innate immunity and hepatic fibrogenesis through the lipopolysaccharide (LPS) toll-like receptor-4 axis. Gut microbiota manipulation through antibiotics, prebiotics and probiotics yields encouraging results for the treatment of obesity, diabetes and NAFLD in animal models, but data in humans are currently scarce. Summary Gut microbiota manipulation yielded encouraging results for the treatment of different metabolic disorders in experimental models. However, changing intestinal microbiota may be more difficult in free-living individuals compared to standardized laboratory models, and its long-term consequences are unknown. To safely and effectively change human gut microflora, future research should highlight the complex hormonal, immunomodulatory and metabolic mechanisms underlying microbiota host interactions in different tissues and candidate treatments should be evaluated in well designed trials with patient-oriented end-points.
引用
收藏
页码:76 / 83
页数:8
相关论文
共 46 条
[1]   Energy intake is associated with endotoxemia in apparently healthy men [J].
Amar, Jacques ;
Burcelin, Remy ;
Ruidavets, Jean Bernard ;
Cani, Patrice D. ;
Fauvel, Josette ;
Alessi, Marie Christine ;
Chamontin, Bernard ;
Ferrieres, Jean .
AMERICAN JOURNAL OF CLINICAL NUTRITION, 2008, 87 (05) :1219-1223
[2]   Innate immunity modulates adipokines in humans [J].
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. .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2007, 92 (06) :2272-2279
[3]   Soft drink consumption linked with fatty liver in the absence of traditional risk factors [J].
Assy, Nimer ;
Nasser, Gattas ;
Kamayse, Iad ;
Nseir, William ;
Beniashvili, Zaza ;
Djibre, Agness ;
Grosovski, Maria .
CANADIAN JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 2008, 22 (10) :811-816
[4]   The gut microbiota as an environmental factor that regulates fat storage [J].
Bäckhed, F ;
Ding, H ;
Wang, T ;
Hooper, LV ;
Koh, GY ;
Nagy, A ;
Semenkovich, CF ;
Gordon, JI .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (44) :15718-15723
[5]   Mechanisms underlying the resistance to diet-induced obesity in germ-free mice [J].
Backhed, Fredrik ;
Manchester, Jill K. ;
Semenkovich, Clay F. ;
Gordon, Jeffrey I. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (03) :979-984
[6]   Antibiotics protect against fructose-induced hepatic lipid accumulation in mice:: Role of endotoxin [J].
Bergheim, Ina ;
Weber, Synia ;
Vos, Miriam ;
Kraemer, Sigrid ;
Volynets, Valentina ;
Kaserouni, Seline ;
McClain, Craig J. ;
Bischoff, Stephan C. .
JOURNAL OF HEPATOLOGY, 2008, 48 (06) :983-992
[7]   Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia [J].
Cani, P. D. ;
Neyrinck, A. M. ;
Fava, F. ;
Knauf, C. ;
Burcelin, R. G. ;
Tuohy, K. M. ;
Gibson, G. R. ;
Delzenne, N. M. .
DIABETOLOGIA, 2007, 50 (11) :2374-2383
[8]   Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability [J].
Cani, P. D. ;
Possemiers, S. ;
Van de Wiele, T. ;
Guiot, Y. ;
Everard, A. ;
Rottier, O. ;
Geurts, L. ;
Naslain, D. ;
Neyrinck, A. ;
Lambert, D. M. ;
Muccioli, G. G. ;
Delzenne, N. M. .
GUT, 2009, 58 (08) :1091-1103
[9]   Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice [J].
Cani, Patrice D. ;
Bibiloni, Rodrigo ;
Knauf, Claude ;
Neyrinck, Audrey M. ;
Neyrinck, Audrey M. ;
Delzenne, Nathalle M. ;
Burcelin, Remy .
DIABETES, 2008, 57 (06) :1470-1481
[10]   Metabolic endotoxemia initiates obesity and insulin resistance [J].
Cani, Patrice D. ;
Amar, Jacques ;
Iglesias, Miguel Angel ;
Poggi, Marjorie ;
Knauf, Claude ;
Bastelica, Delphine ;
Neyrinck, Audrey M. ;
Fava, Francesca ;
Tuohy, Kieran M. ;
Chabo, Chantal ;
Waget, Aurelie ;
Delmee, Evelyne ;
Cousin, Beatrice ;
Sulpice, Thierry ;
Chamontin, Bernard ;
Ferrieres, Jean ;
Tanti, Jean-Francois ;
Gibson, Glenn R. ;
Casteilla, Louis ;
Delzenne, Nathalie M. ;
Alessi, Marie Christine ;
Burcelin, Remy .
DIABETES, 2007, 56 (07) :1761-1772