Abstract
It is now well established that a healthy gut flora is largely responsible for the overall health of the host, while a perturbation in gut microbial communities can contribute to disease susceptibility. Obesity is a complex process involving genetic and environmental factors with an epidemiological burden that makes it a major public health issue. Studies of germ-free or gnotobiotic mice provided evidence that the diversity, as well as the presence and relative proportion of different microbes in the gut play active roles in energy homeostasis. Similarly, human studies showed that both the diversity of the microbiota and the Bacteroidetes/Firmicutes ratio are decreased in obese individuals. The ‘obese microbiota' seems to be able to increase dietary energy harvest and favor weight gain and fat deposition. Although research in this field has just started and many of the available data are still conflicting, the results are providing exciting perspectives, and gut microbiota manipulation has already become a new target for both prevention and treatment of obesity.
References
1.
Sellayah D, Cagampang FR, Cox RD: On the evolutionary origins of obesity: a new hypothesis. Endocrinology 2014;155:1573-1588.
3.
Ranz JM, Casals F, Ruiz A: How malleable is the eukaryotic genome? Extreme rate of chromosomal rearrangement in the genus Drosophila. Genome Res 2001;11:230-239.
4.
McPhee JB, Schertzer JD: Immunometabolism of obesity and diabetes: microbiota link compartmentalized immunity in the gut to metabolic tissue inflammation. Clin Sci (Lond) 2015;129:1083-1096.
5.
Wostmann BS, Larkin C, Moriarty A, Bruckner-Kardoss E: Dietary intake, energy metabolism, and excretory losses of adult male germfree Wistar rats. Lab Anim Sci 1983;33:46-50.
6.
Barlow GM, Yu A, Mathur R: Role of the gut microbiome in obesity and diabetes mellitus. Nutr Clin Pract 2015;30:787-797.
7.
Ussar S, Griffin NW, Bezy O, Fujisaka S, Vienberg S, Softic S, Deng L, Bry L, Gordon JI, Kahn CR: Interactions between gut microbiota, host genetics and diet modulate the predisposition to obesity and metabolic syndrome. Cell Metab 2015;22:516-530.
8.
Rosenbaum M, Knight R, Leibel RL: The gut microbiota in human energy homeostasis and obesity. Trends Endocrinol Metab 2015;26:493-501.
9.
Villanueva-Millán MJ, Pérez-Matute P, Oteo JA: Gut microbiota: a key player in health and disease. A review focused on obesity. J Physiol Biochem 2015;71:509-525.
10.
Hartstra AV, Bouter KE, Bäckhed F, Nieuwdorp M: Insights into the role of the microbiome in obesity and type 2 diabetes. Diabetes Care 2015;38:159-165.
11.
Guarner F, Malagelada JR: Gut flora in health and disease. Lancet 2003;361:512-519.
12.
Frank DN, St Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR: Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A 2007;104:13780-13785.
13.
Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA: Diversity of the human intestinal microbial flora. Science 2005;308:1635-1638.
14.
Shanahan F: The host-microbe interface within the gut. Best Pract Res Clin Gastroenterol 2002;16:915-931.
15.
Xu J, Gordon JI: Honor thy symbionts. Proc Natl Acad Sci U S A 2003;100:10452-10459.
16.
O'Hara AM, Shanahan F: The gut flora as a forgotten organ. EMBO Rep 2006;7:688-693.
17.
Jandhyala SM, Talukdar R, Subramanyam C, Vuyyuru H, Sasikala M, Nageshwar Reddy D: Role of the normal gut microbiota. World J Gastroenterol 2015;21:8787-8803.
18.
Compare D, Nardone G: Contribution of gut microbiota to colonic and extracolonic cancer development. Dig Dis 2011;29:554-561.
19.
Round JL, Mazmanian SK: The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol 2009;9:313-323.
20.
Ley RE, Bäckhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI: Obesity alters gut microbial ecology. Proc Natl Acad Sci U S A 2005;102:11070-11075.
21.
Bäckhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, Semenkovich CF, Gordon JI: The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A 2004;101:15718-15723.
22.
Samuel BS, Gordon JI: A humanized gnotobiotic mouse model of host-archaeal-bacterial mutualism. Proc Natl Acad Sci U S A 2006;103:10011-10016.
23.
Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI: An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006;444:1027-1031.
24.
Ridaura VK, Faith JJ, Rey FE, Cheng J, Duncan AE, Kau AL, Griffin NW, Lombard V, Henrissat B, Bain JR, Muehlbauer MJ, Ilkayeva O, Semenkovich CF, Funai K, Hayashi DK, Lyle BJ, Martini MC, Ursell LK, Clemente JC, Van Treuren W, Walters WA, Knight R, Newgard CB, Heath AC, Gordon JI: Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 2013;341:1241214.
25.
Cox LM, Yamanishi S, Sohn J, Alekseyenko AV, Leung JM, Cho I, Kim SG, Li H, Gao Z, Mahana D, Zárate Rodriguez JG, Rogers AB, Robine N, Loke P, Blaser MJ: Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell 2014;158:705-721.
26.
Hildebrandt MA, Hoffmann C, Sherrill-Mix SA, Keilbaugh SA, Hamady M, Chen YY, Knight R, Ahima RS, Bushman F, Wu GD: High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology 2009;137:1716-1724.
27.
Turnbaugh PJ, Bäckhed F, Fulton L, Gordon JI: Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe 2008;3:213-223.
28.
Schneeberger M, Everard A, Gómez-Valadés AG, Matamoros S, Ramírez S, Delzenne NM, Gomis R, Claret M, Cani PD: Akkermansia muciniphila inversely correlates with the onset of inflammation, altered adipose tissue metabolism and metabolic disorders during obesity in mice. Sci Rep 2015;5:16643.
29.
Ravussin Y, Koren O, Spor A, LeDuc C, Gutman R, Stombaugh J, Knight R, Ley RE, Leibel RL: Responses of gut microbiota to diet composition and weight loss in lean and obese mice. Obesity (Silver Spring) 2012;20:738-747.
30.
Stemmer K, Kotzbeck P, Zani F, Bauer M, Neff C, Müller TD, Pfluger PT, Seeley RJ, Divanovic S: Thermoneutral housing is a critical factor for immune function and diet-induced obesity in C57BL/6 nude mice. Int J Obes (Lond) 2015;39:791-797.
31.
Bailey LC, Forrest CB, Zhang P, Richards TM, Livshits A, DeRusso PA: Association of antibiotics in infancy with early childhood obesity. JAMA Pediatr 2014;168:1063-1069.
32.
Owen CG, Martin RM, Whincup PH, Davey-Smith G, Gillman MW, Cook DG: The effect of breastfeeding on mean body mass index throughout life: a quantitative review of published and unpublished observational evidence. Am J Clin Nutr 2005;82:1298-1307.
33.
Hunt KM, Foster JA, Forney LJ, Schütte UM, Beck DL, Abdo Z, Fox LK, Williams JE, McGuire MK, McGuire MA: Characterization of the diversity and temporal stability of bacterial communities in human milk. PLoS One 2011;6:e21313.
34.
den Besten G, van Eunen K, Groen AK, Venema K, Reijngoud DJ, Bakker BM: The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res 2013;54:2325-2340.
35.
Musso G, Gambino R, Cassader M: Obesity, diabetes, and gut microbiota: the hygiene hypothesis expanded? Diabetes Care 2010;33:2277-2284.
36.
Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, Sogin ML, Jones WJ, Roe BA, Affourtit JP, Egholm M, Henrissat B, Heath AC, Knight R, Gordon JI: A core gut microbiome in obese and lean twins. Nature 2009;457:480-484.
37.
Walters WA, Xu Z, Knight R: Meta-analyses of human gut microbes associated with obesity and IBD. FEBS Lett 2014;588:4223-4233.
38.
De Bandt JP, Waligora-Dupriet AJ, Butel MJ: Intestinal microbiota in inflammation and insulin resistance: relevance to humans. Curr Opin Clin Nutr Metab Care 2011;14:334-340.
39.
Cotillard A, Kennedy SP, Kong LC, Prifti E, Pons N, Le Chatelier E, Almeida M, Quinquis B, Levenez F, Galleron N, Gougis S, Rizkalla S, Batto JM, Renault P; ANR MicroObes Consortium, Doré J, Zucker JD, Clément K, Ehrlich SD: Dietary intervention impact on gut microbial gene richness. Nature 2013;500:585-588.
40.
Zhang H, DiBaise JK, Zuccolo A, Kudrna D, Braidotti M, Yu Y, Parameswaran P, Crowell MD, Wing R, Rittmann BE, Krajmalnik-Brown R: Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci U S A 2009;106:2365-2370.
41.
Dao MC, Everard A, Aron-Wisnewsky J, Sokolovska N, Prifti E, Verger EO, Kayser BD, Levenez F, Chilloux J, Hoyles L; MICRO-Obes Consortium, Dumas ME, Rizkalla SW, Doré J, Cani PD, Clément K: Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut 2015;pii:gutjnl-2014-308778.
42.
Verdam FJ, Fuentes S, de Jonge C, Zoetendal EG, Erbil R, Greve JW, Buurman WA, de Vos WM, Rensen SS: Human intestinal microbiota composition is associated with local and systemic inflammation in obesity. Obesity (Silver Spring) 2013;21:E607-E615.
43.
Ferrer M, Ruiz A, Lanza F, Haange SB, Oberbach A, Till H, Bargiela R, Campoy C, Segura MT, Richter M, von Bergen M, Seifert J, Suarez A: Microbiota from the distal guts of lean and obese adolescents exhibit partial functional redundancy besides clear differences in community structure. Environ Microbiol 2013;15:211-226.
44.
Tims S, Derom C, Jonkers DM, Vlietinck R, Saris WH, Kleerebezem M, de Vos WM, Zoetendal EG: Microbiota conservation and BMI signatures in adult monozygotic twins. ISME J 2013;7:707-717.
45.
Walters WA, Xu Z, Knight R: Meta-analyses of human gut microbes associated with obesity and IBD. FEBS Lett 2014;588:4223-4233.
46.
Furet JP, Kong LC, Tap J, Poitou C, Basdevant A, Bouillot JL, Mariat D, Corthier G, Doré J, Henegar C, Rizkalla S, Clément K: Differential adaptation of human gut microbiota to bariatric surgery-induced weight loss: links with metabolic and low-grade inflammation markers. Diabetes 2010;59:3049-3057.
47.
Tremaroli V, Karlsson F, Werling M, Ståhlman M, Kovatcheva-Datchary P, Olbers T, Fändriks L, le Roux CW, Nielsen J, Bäckhed F: Roux-en-Y gastric bypass and vertical banded gastroplasty induce long-term changes on the human gut microbiome contributing to fat mass regulation. Cell Metab 2015;22:228-238.
48.
Mar Rodríguez M, Pérez D, Javier Chaves F, Esteve E, Marin-Garcia P, Xifra G, Vendrell J, Jové M, Pamplona R, Ricart W, Portero-Otin M, Chacón MR, Fernández Real JM: Obesity changes the human gut mycobiome. Sci Rep 2015;5:14600.
49.
Compare D, Coccoli P, Rocco A, Nardone OM, De Maria S, Cartenì M, Nardone G: Gut-liver axis: the impact of gut microbiota on non alcoholic fatty liver disease. Nutr Metab Cardiovasc Dis 2012;22:471-476.
50.
Tilg H, Moschen AR: Microbiota and diabetes: an evolving relationship. Gut 2014;63:1513-1521.
51.
Tilg H, Kaser A: Gut microbiome, obesity, and metabolic dysfunction. J Clin Invest 2011;121:2126-2132.
52.
Moreira AP, Texeira TF, Ferreira AB, Peluzio Mdo C, Alfenas Rde C: Influence of a high-fat diet on gut microbiota, intestinal permeability and metabolic endotoxaemia. Br J Nutr 2012;108:801-809.
53.
de Punder K, Pruimboom L: Stress induces endotoxemia and low-grade inflammation by increasing barrier permeability. Front Immunol 2015;6:223.
54.
Neves AL, Coelho J, Couto L, Leite-Moreira A, Roncon-Albuquerque R Jr: Metabolic endotoxemia: a molecular link between obesity and cardiovascular risk. J Mol Endocrinol 2013;51:R51-R64.
55.
de La Serre CB, Ellis CL, Lee J, Hartman AL, Rutledge JC, Raybould HE: Propensity to high-fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammation. Am J Physiol Gastrointest Liver Physiol 2010;299:G440-G448.
56.
Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C, Waget A, Delmée E, Cousin B, Sulpice T, Chamontin B, Ferrières J, Tanti JF, Gibson GR, Casteilla L, Delzenne NM, Alessi MC, Burcelin R: Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 2007;56:1761-1772.
57.
Bäckhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI: Host-bacterial mutualism in the human intestine. Science 2005;307:1915-1920.
58.
Blaut M: Gut microbiota and energy balance: role in obesity. Proc Nutr Soc 2015;74:227-234.
59.
Chambers ES, Morrison DJ, Frost G: Control of appetite and energy intake by SCFA: what are the potential underlying mechanisms? Proc Nutr Soc 2015;74:328-336.
60.
Brown AJ, Goldsworthy SM, Barnes AA, Eilert MM, Tcheang L, Daniels D, Muir AI, Wigglesworth MJ, Kinghorn I, Fraser NJ, Pike NB, Strum JC, Steplewski KM, Murdock PR, Holder JC, Marshall FH, Szekeres PG, Wilson S, Ignar DM, Foord SM, Wise A, Dowell SJ: The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem 2003;278:11312-11319.
61.
Bjursell M, Admyre T, Göransson M, Marley AE, Smith DM, Oscarsson J, Bohlooly-Y M: Improved glucose control and reduced body fat mass in free fatty acid receptor 2-deficient mice fed a high-fat diet. Am J Physiol Endocrinol Metab 2011;300:E211-E220.
62.
Samuel BS, Shaito A, Motoike T, Rey FE, Backhed F, Manchester JK, Hammer RE, Williams SC, Crowley J, Yanagisawa M, Gordon JI: Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc Natl Acad Sci U S A 2008;105:16767-16772.
63.
Kim HK, Youn BS, Shin MS, Namkoong C, Park KH, Baik JH, Kim JB, Park JY, Lee KU, Kim YB, Kim MS: Hypothalamic Angptl4/Fiaf is a novel regulator of food intake and body weight. Diabetes 2010;59:2772-2780.
64.
Fu X, Zhu M, Zhang S, Foretz M, Viollet B, Du M: Obesity impairs skeletal muscle regeneration via inhibition of AMP-activated protein kinase. Diabetes 2015;pii:db150647.
65.
Bäckhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, Semenkovich CF, Gordon JI: The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A 2004;101:15718-15723.
66.
Lopategi A, López-Vicario C, Alcaraz-Quiles J, García-Alonso V, Rius B, Titos E, Clària J: Role of bioactive lipid mediators in obese adipose tissue inflammation and endocrine dysfunction. Mol Cell Endocrinol 2016;419:44-59.
67.
Bauer PV, Hamr SC, Duca FA: Regulation of energy balance by a gut-brain axis and involvement of the gut microbiota. Cell Mol Life Sci 2015, Epub ahead of print.
68.
Schéle E, Grahnemo L, Anesten F, Hallén A, Bäckhed F, Jansson JO: The gut microbiota reduces leptin sensitivity and the expression of the obesity-suppressing neuropeptides proglucagon (Gcg) and brain-derived neurotrophic factor (Bdnf) in the central nervous system. Endocrinology 2013;154:3643-3651.
69.
Vijay-Kumar M, Aitken JD, Carvalho FA, Cullender TC, Mwangi S, Srinivasan S, Sitaraman SV, Knight R, Ley RE, Gewirtz AT: Metabolic syndrome and altered gut microbiota in mice lacking toll-like receptor 5. Science 2010;328:228-231.
70.
Shen J, Obin MS, Zhao L: The gut microbiota, obesity and insulin resistance. Mol Aspects Med 2013;34:39-58.
71.
Moreno-Indias I, Cardona F, Tinahones FJ, Queipo-Ortuño MI: Impact of the gut microbiota on the development of obesity and type 2 diabetes mellitus. Front Microbiol 2014;5:190.
72.
Chen J, He X, Huang J: Diet effects in gut microbiome and obesity. J Food Sci 2014;79:R442-R451.
73.
Pai MP, Bearden DT: Antimicrobial dosing considerations in obese adult patients. Pharmacotherapy 2007;27:1081-1091.
74.
Falagas ME, Karageorgopoulos DE: Adjustment of dosing of antimicrobial agents for bodyweight in adults. Lancet 2010;375:248-251.
75.
Capurso L, Morelli L: Probiotics and European food safety authority health claims. J Clin Gastroenterol 2010;44(suppl 1):S1.
76.
Zarrati M, Shidfar F, Nourijelyani K, Mofid V, Hossein zadeh-Attar MJ, Bidad K, Najafi F, Gheflati Z, Chamari M, Salehi E: Lactobacillus acidophilus La5, Bifidobacterium BB12, and Lactobacillus casei DN001 modulate gene expression of subset specific transcription factors and cytokines in peripheral blood mononuclear cells of obese and overweight people. Biofactors 2013;39:633-643.
77.
Gøbel RJ, Larsen N, Jakobsen M, Mølgaard C, Michaelsen KF: Probiotics to adolescents with obesity: effects on inflammation and metabolic syndrome. J Pediatr Gastroenterol Nutr 2012;55:673-678.
78.
Sharafedtinov KK, Plotnikova OA, Alexeeva RI, Sentsova TB, Songisepp E, Stsepetova J, Smidt I, Mikelsaar M: Hypocaloric diet supplemented with probiotic cheese improves body mass index and blood pressure indices of obese hypertensive patients - a randomized double-blind placebo-controlled pilot study. Nutr J 2013;12:138.
79.
Lee SJ, Bose S, Seo JG, Chung WS, Lim CY, Kim H: The effects of co-administration of probiotics with herbal medicine on obesity, metabolic endotoxemia and dysbiosis: a randomized double-blind controlled clinical trial. Clin Nutr 2014;33:973-981.
80.
Park S, Bae JH: Probiotics for weight loss: a systematic review and meta-analysis. Nutr Res 2015;35:566-575.
81.
Pineiro M, Asp NG, Reid G, Macfarlane S, Morelli L, Brunser O, Tuohy K: FAO technical meeting on prebiotics. J Clin Gastroenterol 2008;42(suppl 3):S156-S159.
82.
Seidel C, Boehm V, Vogelsang H, Wagner A, Persin C, Glei M, Pool-Zobel BL, Jahreis G: Influence of prebiotics and antioxidants in bread on the immune system, antioxidative status and antioxidative capacity in male smokers and non-smokers. Br J Nutr 2007;97:349-356.
83.
Parnell JA, Reimer RA: Weight loss during oligofructose supplementation is associated with decreased ghrelin and increased peptide YY in overweight and obese adults. Am J Clin Nutr 2009;89:1751-1759.
84.
Genta S, Cabrera W, Habib N, Pons J, Carillo IM, Grau A, Sánchez S: Yacon syrup: beneficial effects on obesity and insulin resistance in humans. Clin Nutr 2009;28:182-187.
85.
de Luis DA, de la Fuente B, Izaola O, Conde R, Gutiérrez S, Morillo M, Teba Torres C: Double blind randomized clinical trial controlled by placebo with an alpha linoleic acid and prebiotic enriched cookie on risk cardiovascular factor in obese patients. Nutr Hosp 2011;26:827-833.
86.
Dehghan P, Gargari BP, Jafar-Abadi MA, Aliasgharzadeh A: Inulin controls inflammation and metabolic endotoxemia in women with type 2 diabetes mellitus: a randomized-controlled clinical trial. Int J Food Sci Nutr 2014;65:117-123.
87.
Kellow NJ, Coughlan MT, Reid CM: Metabolic benefits of dietary prebiotics in human subjects: a systematic review of randomised controlled trials. Br J Nutr 2014;111:1147-1161.
88.
Vrieze A, Van Nood E, Holleman F, Salojärvi J, Kootte RS, Bartelsman JF, Dallinga-Thie GM, Ackermans MT, Serlie MJ, Oozeer R, Derrien M, Druesne A, Van Hylckama Vlieg JE, Bloks VW, Groen AK, Heilig HG, Zoetendal EG, Stroes ES, de Vos WM, Hoekstra JB, Nieuwdorp M: Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology 2012;143:913-916.
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