Childhood obesity: a role for gut microbiota?

Marina Sanchez, Shirin Panahi, Angelo Tremblay, Marina Sanchez, Shirin Panahi, Angelo Tremblay

Abstract

Obesity is a serious public health issue affecting both children and adults. Prevention and management of obesity is proposed to begin in childhood when environmental factors exert a long-term effect on the risk for obesity in adulthood. Thus, identifying modifiable factors may help to reduce this risk. Recent evidence suggests that gut microbiota is involved in the control of body weight, energy homeostasis and inflammation and thus, plays a role in the pathophysiology of obesity. Prebiotics and probiotics are of interest because they have been shown to alter the composition of gut microbiota and to affect food intake and appetite, body weight and composition and metabolic functions through gastrointestinal pathways and modulation of the gut bacterial community. As shown in this review, prebiotics and probiotics have physiologic functions that contribute to changes in the composition of gut microbiota, maintenance of a healthy body weight and control of factors associated with childhood obesity through their effects on mechanisms controlling food intake, fat storage and alterations in gut microbiota.

Figures

Figure 1
Figure 1
Dysbiosis in the gut microbiota may lead to obesity via different mechanisms. (A) An imbalance in intestinal microbiota leads to an increase in SCFA and gut permeability and decrease in FIAF and AMPK; and (B) A restored microbiota by prebiotics and/or probiotics may inhibit the mechanisms described in (A) and lead to an increase in the hormones PYY and GLP-1 and decrease in ghrelin.

References

    1. Brien S.E., Katzmarzyk P.T. Physical activity and the metabolic syndrome in Canada. Appl. Physiol. Nutr. Metab. 2006;31:40–47. doi: 10.1139/h05-024.
    1. Whitaker R.C., Wright J.A., Pepe M.S., Seidel K.D., Dietz W.H. Predicting obesity in young adulthood from childhood and parental obesity. N. Engl. J. Med. 1997;337:869–873. doi: 10.1056/NEJM199709253371301.
    1. Smith J.D., Montano Z., Dishion T.J., Shaw D.S., Wilson M.N. Preventing weight gain and obesity: Indirect effects of the family check-up in early childhood. Prev. Sci. 2014 doi: 10.1007/s11121-014-0505-z.
    1. Chaput J.P., Despres J.P., Bouchard C., Tremblay A. Longer sleep duration associates with lower adiposity gain in adult short sleepers. Int. J. Obes. 2012;36:752–756. doi: 10.1038/ijo.2011.110.
    1. Zemel M.B., Thompson W., Milstead A., Morris K., Campbell P. Calcium and dairy acceleration of weight and fat loss during energy restriction in obese adults. Obes. Res. 2004;12:582–590. doi: 10.1038/oby.2004.67.
    1. Chaput J.P., Leblanc C., Perusse L., Despres J.P., Bouchard C., Tremblay A. Risk factors for adult overweight and obesity in the quebec family study: Have we been barking up the wrong tree? Obesity. 2009;17:1964–1970. doi: 10.1038/oby.2009.116.
    1. Bervoets L., Van Hoorenbeeck K., Kortleven I., Van Noten C., Hens N., Vael C., Goossens H., Desager K.N., Vankerckhoven V. Differences in gut microbiota composition between obese and lean children: A cross-sectional study. Gut Pathog. 2013;5 doi: 10.1186/1757-4749-5-10.
    1. Bouchard C., Tremblay A., Despres J.P., Nadeau A., Lupien P.J., Theriault G., Dussault J., Moorjani S., Pinault S., Fournier G. The response to long-term overfeeding in identical twins. N. Engl. J. Med. 1990;322:1477–1482. doi: 10.1056/NEJM199005243222101.
    1. Backhed F., Ding H., Wang T., Hooper L.V., Koh G.Y., Nagy A., Semenkovich C.F., Gordon J.I. The gut microbiota as an environmental factor that regulates fat storage. Proc. Nat. Acad. Sci. USA. 2004;101:15718–15723. doi: 10.1073/pnas.0407076101.
    1. Backhed F., Manchester J.K., Semenkovich C.F., Gordon J.I. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc. Nat. Acad. Sci. USA. 2007;104:979–984. doi: 10.1073/pnas.0605374104.
    1. Turnbaugh P.J., Gordon J.I. The core gut microbiome, energy balance and obesity. J. Physiol. 2009;587:4153–4158. doi: 10.1113/jphysiol.2009.174136.
    1. Turnbaugh P.J., Ley R.E., Mahowald M.A., Magrini V., Mardis E.R., Gordon J.I. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444:1027–1031. doi: 10.1038/nature05414.
    1. Kadooka Y., Sato M., Imaizumi K., Ogawa A., Ikuyama K., Akai Y., Okano M., Kagoshima M., Tsuchida T. Regulation of abdominal adiposity by probiotics (Lactobacillus gasseri SBT2055) in adults with obese tendencies in a randomized controlled trial. Eur. J. Clin. Nutr. 2010;64:636–643. doi: 10.1038/ejcn.2010.19.
    1. Chang B.J., Park S.U., Jang Y.S., Ko S.H., Joo N.M., Kim S.I., Kim C.H., Chang D.K. Effect of functional yogurt NY-YP901 in improving the trait of metabolic syndrome. Eur. J. Clin. Nutr. 2011;65:1250–1255. doi: 10.1038/ejcn.2011.115.
    1. Omar J.M., Chan Y.-M., Jones M.L., Prakash S., Jones P.J.H. Lactobacillus fermentum and Lactobacillus amylovorus as probiotics alter body adiposity and gut microflora in healthy persons. J. Funct. Foods. 2013;5:116–123. doi: 10.1016/j.jff.2012.09.001.
    1. Zarrati M., Salehi E., Nourijelyani K., Mofid V., Zadeh M.J., Najafi F., Ghaflati Z., Bidad K., Chamari M., Karimi M., et al. Effects of probiotic yogurt on fat distribution and gene expression of proinflammatory factors in peripheral blood mononuclear cells in overweight and obese people with or without weight-loss diet. J. Amer. Coll. Nutr. 2014;33:417–425. doi: 10.1080/07315724.2013.874937.
    1. Kang J.H., Yun S.I., Park H.O. Effects of Lactobacillus gasseri BNR17 on body weight and adipose tissue mass in diet-induced overweight rats. J. Microbiol. 2010;48:712–714. doi: 10.1007/s12275-010-0363-8.
    1. Piche T., des Varannes S.B., Sacher-Huvelin S., Holst J.J., Cuber J.C., Galmiche J.P. Colonic fermentation influences lower esophageal sphincter function in gastroesophageal reflux disease. Gastroenterology. 2003;124:894–902. doi: 10.1053/gast.2003.50159.
    1. Cani P.D., Bibiloni R., Knauf C., Waget A., Neyrinck A.M., Delzenne N.M., Burcelin R. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes. 2008;57:1470–1481. doi: 10.2337/db07-1403.
    1. Cani P.D., Delzenne N.M. Interplay between obesity and associated metabolic disorders: New insights into the gut microbiota. Curr. Opin. Pharmacol. 2009;9:737–743. doi: 10.1016/j.coph.2009.06.016.
    1. Cani P.D., Delzenne N.M. The gut microbiome as therapeutic target. Pharmacol. Ther. 2011;130:202–212. doi: 10.1016/j.pharmthera.2011.01.012.
    1. Hill J.O., Peters J.C. Environmental contributions to the obesity epidemic. Science. 1998;280:1371–1374. doi: 10.1126/science.280.5368.1371.
    1. Delzenne N.M., Cani P.D. Interaction between obesity and the gut microbiota: Relevance in nutrition. Annu. Rev. Nutr. 2011;31:15–31. doi: 10.1146/annurev-nutr-072610-145146.
    1. Ley R.E., Turnbaugh P.J., Klein S., Gordon J.I. Microbial ecology: Human gut microbes associated with obesity. Nature. 2006;444:1022–1023. doi: 10.1038/4441022a.
    1. Turnbaugh P.J., Hamady M., Yatsunenko T., Cantarel B.L., Duncan A., Ley R.E., Sogin M.L., Jones W.J., Roe B.A., Affourtit J.P., et al. A core gut microbiome in obese and lean twins. Nature. 2009;457:480–484. doi: 10.1038/nature07540.
    1. Jumpertz R., Le D., Turnbaugh P., Trinidad C., Bogardus C., Gordon J., Krakoff J. Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans. Amer. J. Clin. Nutr. 2011;94:58–65. doi: 10.3945/ajcn.110.010132.
    1. Vael C., Verhulst S.L., Nelen V., Goossens H., Desager K.N. Intestinal microflora and body mass index during the first three years of life: An observational study. Gut Pathog. 2011;3 doi: 10.1186/1757-4749-3-8.
    1. Luoto R., Kalliomaki M., Laitinen K., Delzenne N.M., Cani P.D., Salminen S., Isolauri E. Initial dietary and microbiological environments deviate in normal-weight compared to overweight children at 10 years of age. J. Pediatr. Gastroenterol. Nutr. 2011;52:90–95. doi: 10.1097/MPG.0b013e3181f3457f.
    1. Hildebrandt M.A., Hoffmann C., Sherrill-Mix S.A., Keilbaugh S.A., Hamady M., Chen Y.Y., Knight R., Ahima R.S., Bushman F., Wu G.D. High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology. 2009;137:1716–1724. doi: 10.1053/j.gastro.2009.08.042.
    1. Mackie R.I., Sghir A., Gaskins H.R. Developmental microbial ecology of the neonatal gastrointestinal tract. Amer. J. Clin. Nutr. 1999;69:S1035–S1045.
    1. Palmer C., Bik E.M., DiGiulio D.B., Relman D.A., Brown P.O. Development of the human infant intestinal microbiota. PLoS Biol. 2007;5 doi: 10.1371/journal.pbio.0050177.
    1. Koenig J.E., Spor A., Scalfone N., Fricker A.D., Stombaugh J., Knight R., Angenent L.T., Ley R.E. Succession of microbial consortia in the developing infant gut microbiome. Proc. Nat. Acad. Sci. USA. 2011;108:S4578–S4585. doi: 10.1073/pnas.1000081107.
    1. Turnbaugh P.J., Backhed F., Fulton L., Gordon J.I. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell. Host Microbe. 2008;3:213–223. doi: 10.1016/j.chom.2008.02.015.
    1. Gibson G.R., Roberfroid M.B. Dietary modulation of the human colonic microbiota: Introducing the concept of prebiotics. J. Nutr. 1995;125:1401–1412.
    1. Roberfroid M. Prebiotics: The concept revisited. J. Nutr. 2007;137:S830–S837.
    1. Geier M., Butler R., Howarth G. Inflammatory bowel disease: Current insights into pathogenesis and new therapeutic options: Probiotics, prebiotics and synbiotics. Int. J. Food Microbiol. 2007;115:1–11. doi: 10.1016/j.ijfoodmicro.2006.10.006.
    1. Hedin C., Whelan K., Lindsay J. Evidence for the use of probiotics and prebiotics in inflammatory bowel disease: A review of clinical trials. Proc. Nutr. Soc. 2007;66:307–315. doi: 10.1017/S0029665107005563.
    1. Lomax A.R., Calder P.C. Prebiotics, immune function, infection and inflammation: A review of the evidence. Brit. J. Nutr. 2009;101:633–658. doi: 10.1017/S0007114508055608.
    1. Yeo S.K., Ooi L.G., Lim T.J., Liong M.T. Antihypertensive properties of plant-based prebiotics. Int. J. Mol. Sci. 2009;10:3517–3530. doi: 10.3390/ijms10083517.
    1. Flamm G., Glinsmann W., Kirtchevsky D., Prosky L., Roberfroid M. Inulin and oligofructose as dietary fiber: A review of the evidence. Crit. Rev. Food Sci. Nutr. 2001;41:353–362. doi: 10.1080/20014091091841.
    1. FAO/WHO Working Group . Guidelines for the Evaluation of Probiotics in Food. FAO; London, ON, Canada: 2002.
    1. Saraf K., Shashikanth M., Priy T., Sultana N., Chaitanya N. Probiotics—Do they have a role in medicine and dentistry? J. Assoc. Physic. India. 2010;58:488–490, 495–496.
    1. Vanderpool C., Yan F., Polk D.B. Mechanisms of probiotic action: Implications for therapeutic applications in inflammatory bowel diseases. Inflamm. Bowel Dis. 2008;14:1585–1596. doi: 10.1002/ibd.20525.
    1. De Vrese M., Marteau P.R. Probiotics and prebiotics: Effects on diarrhea. J. Nutr. 2007;137:S803–S811.
    1. Minocha A. Probiotics for preventive health. Nutr. Clin. Pract. 2009;24:227–241. doi: 10.1177/0884533608331177.
    1. Azcarate-Peril M.A., Sikes M., Bruno-Barcena J.M. The intestinal microbiota, gastrointestinal environment and colorectal cancer: A putative role for probiotics in prevention of colorectal cancer? Amer. J. Physiol. Gastrointest. Liver Physiol. 2011;301:401–424. doi: 10.1152/ajpgi.00110.2011.
    1. Singh M., Ranjan Das R. Probiotics for allergic respiratory diseases—Putting it into perspective. Pediatr. Allergy Immunol. 2010;21:1399–3038. doi: 10.1111/j.1399-3038.2009.00921.x.
    1. Tang M.L., Lahtinen S.J., Boyle R.J. Probiotics and prebiotics: Clinical effects in allergic disease. Curr. Opin. Pediatr. 2010;22:626–634.
    1. Borchers A.T., Selmi C., Meyers F.J., Keen C.L., Gershwin M.E. Probiotics and immunity. J. Gastroenterol. 2009;44:26–46. doi: 10.1007/s00535-008-2296-0.
    1. Desbonnet L., Garrett L., Clarke G., Kiely B., Cryan J.F., Dinan T.G. Effects of the probiotic bifidobacterium infantis in the maternal separation model of depression. Neuroscience. 2010;170:1179–1188. doi: 10.1016/j.neuroscience.2010.08.005.
    1. Bravo J.A., Forsythe P., Chew M.V., Escaravage E., Savignac H.M., Dinan T.G., Bienenstock J., Cryan J.F. Ingestion of Lactobacillus strain regulates emotional behavior and central gaba receptor expression in a mouse via the vagus nerve. Proc. Nat. Acad. Sci. USA. 2011;108:16050–16055. doi: 10.1073/pnas.1102999108.
    1. Lye H.S., Rusul G., Liong M.T. Removal of cholesterol by Lactobacilli via incorporation and conversion to coprostanol. J. Dairy Sci. 2010;93:1383–1392. doi: 10.3168/jds.2009-2574.
    1. Saxelin M., Lassig A., Karjalainen H., Tynkkynen S., Surakka A., Vapaatalo H., Järvenpää S., Korpela R., Mutanen M., Hatakka K. Persistence of probiotic strains in the gastrointestinal tract when administered as capsules, yoghurt, or cheese. Int. J. Food Microbiol. 2010;144:293–300. doi: 10.1016/j.ijfoodmicro.2010.10.009.
    1. Samuel B.S., Shaito A., Motoike T., Rey F.E., Backhed F., Manchester J.K., Hammer R.E., Williams S.C., Crowley J., Yanagisawa M., et al. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, GPR41. Proc. Nat. Acad. Sci. USA. 2008;105:16767–16772. doi: 10.1073/pnas.0808567105.
    1. Bjursell M., Admyre T., Göransson M., Marley A.E., Smith D.M., 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. Amer. J. Physiol. Endocrinol. Metab. 2011;300:211–220. doi: 10.1152/ajpendo.00229.2010.
    1. Parnell J.A., Reimer R.A. Weight loss during oligofructose supplementation is associated with decreased ghrelin and increased peptide YY in overweight and obese adults. Amer. J. Clin. Nutr. 2009;89:1751–1759. doi: 10.3945/ajcn.2009.27465.
    1. Cani P.D., Lecourt E., Dewulf E.M., Sohet F.M., Pachikian B.D., Naslain D., De Backer F., Neyrinck A.M., Delzenne N.M. Gut microbiota fermentation of prebiotics increases satietogenic and incretin gut peptide production with consequences for appetite sensation and glucose response after a meal. Amer. J. Clin. Nutr. 2009;90:1236–1243. doi: 10.3945/ajcn.2009.28095.
    1. Cani P.D., Dewever C., Delzenne N.M. Inulin-type fructans modulate gastrointestinal peptides involved in appetite regulation (glucagon-like peptide-1 and ghrelin) in rats. Brit. J. Nutr. 2004;92:521–526. doi: 10.1079/BJN20041225.
    1. Wettergren A., Schjoldager B., Mortensen P.E., Myhre J., Christiansen J., Holst J.J. Truncated GLP-1 (proglucagon 78–107-amide) inhibits gastric and pancreatic functions in man. Dig. Dis. Sci. 1993;38:665–673. doi: 10.1007/BF01316798.
    1. Delzenne N.M., Cani P.D. Gut microflora is a key player in host energy homeostasis. Med. Sci. 2008;24:505–510.
    1. Brun P., Castagliuolo I., Di Leo V., Buda A., Pinzani M., Palu G., Martines D. Increased intestinal permeability in obese mice: New evidence in the pathogenesis of nonalcoholic steatohepatitis. Amer. J. Physiol.-Gastrointest. L. 2007;292:518–525. doi: 10.1152/ajpgi.00024.2006.
    1. De La Serre C.B., Ellis C.L., Lee J., Hartman A.L., Rutledge J.C., Raybould H.E. Propensity to high-fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammation. Amer. J. Physiol. Gastrointest.-L. 2010;299:440–448. doi: 10.1152/ajpgi.00098.2010.
    1. Muccioli G.G., Naslain D., Backhed F., Reigstad C.S., Lambert D.M., Delzenne N.M., Cani P.D. The endocannabinoid system links gut microbiota to adipogenesis. Mol. Syst. Biol. 2010;6 doi: 10.1038/msb.2010.46.
    1. Amar J., Burcelin R., Ruidavets J.B., Cani P.D., Fauvel J., Alessi M.C., Chamontin B., Ferrieres J. Energy intake is associated with endotoxemia in apparently healthy men. Amer. J. Clin. Nutr. 2008;87:1219–1223.
    1. Fried S.K., Bunkin D.A., Greenberg A.S. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: Depot difference and regulation by glucocorticoid. J. Clin. Endocrinol. Metab. 1998;83:847–850.
    1. Caesar R., Reigstad C.S., Backhed H.K., Reinhardt C., Ketonen M., Lunden G.O., Cani P.D., Backhed F. Gut-derived lipopolysaccharide augments adipose macrophage accumulation but is not essential for impaired glucose or insulin tolerance in mice. Gut. 2012;61:1701–1707. doi: 10.1136/gutjnl-2011-301689.
    1. Hotamisligil G.S. Inflammation and metabolic disorders. Nature. 2006;444:860–867. doi: 10.1038/nature05485.
    1. Shoelson S.E., Lee J., Goldfine A.B. Inflammation and insulin resistance. J. Clin. Invest. 2006;116:1793–1801. doi: 10.1172/JCI29069.
    1. Puigserver P., Spiegelman B.M. Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): Transcriptional coactivator and metabolic regulator. Endocr. Rev. 2003;24:78–90. doi: 10.1210/er.2002-0012.
    1. Ranganath L.R., Beety J.M., Morgan L.M., Wright J.W., Howland R., Marks V. Attenuated GLP-1 secretion in obesity: Cause or consequence? Gut. 1996;38:916–919. doi: 10.1136/gut.38.6.916.
    1. Neary M.T., Batterham R.L. Gut hormones: Implications for the treatment of obesity. Pharmacol. Ther. 2009;124:44–56. doi: 10.1016/j.pharmthera.2009.06.005.
    1. Musso G., Gambino R., Cassader M. Gut microbiota as a regulator of energy homeostasis and ectopic fat deposition: Mechanisms and implications for metabolic disorders. Curr. Opin. Lipidol. 2010;21:76–83. doi: 10.1097/MOL.0b013e3283347ebb.
    1. Cani P.D., Possemiers S., Van de Wiele T., Guiot Y., Everard A., Rottier O., Geurts L., Naslain D., Neyrinck A., Lambert D.M., et al. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut. 2009;58:1091–1103. doi: 10.1136/gut.2008.165886.
    1. Delzenne N.M., Cani P.D., Daubioul C., Neyrinck A.M. Impact of inulin and oligofructose on gastrointestinal peptides. Brit. J. Nutr. 2005;93:S157–S161. doi: 10.1079/BJN20041342.
    1. Forssten S.D., Korczynska M.Z., Zwijsen R.M., Noordman W.H., Madetoja M., Ouwehand A.C. Changes in satiety hormone concentrations and feed intake in rats in response to lactic acid bacteria. Appetite. 2013;71:16–21. doi: 10.1016/j.appet.2013.06.093.
    1. Ruijschop R., Boelrijk A., te Giffel M. Satiety effects of a dairy beverage fermented with propionic acid bacteria. Int. Dairy J. 2008;8:945–950. doi: 10.1016/j.idairyj.2008.01.004.
    1. Alisi A., Bedogni G., Baviera G., Giorgio V., Porro E., Paris C., Giammaria P., Reali L., Anania F., Nobili V. Randomised clinical trial: The beneficial effects of VSL#3 in obese children with non-alcoholic steatohepatitis. Aliment. Pharmacol. Ther. 2014;39:1276–1285. doi: 10.1111/apt.12758.
    1. Sanchez M., Darimont C., Drapeau V., Emady-Azar S., Lepage M., Rezzonico E., Ngom-Bru C., Berger B., Philippe L., Ammon-Zuffrey C., et al. Effect of Lactobacillus rhamnosus CGMCC1.3724 supplementation on weight loss and maintenance in obese men and women. Brit. J. Nutr. 2014;111:1507–1519. doi: 10.1017/S0007114513003875.
    1. Safavi M., Farajian S., Kelishadi R., Mirlohi M., Hashemipour M. The effects of synbiotic supplementation on some cardio-metabolic risk factors in overweight and obese children: A randomized triple-masked controlled trial. Int. J. Food Sci. Nutr. 2013;64:687–693. doi: 10.3109/09637486.2013.775224.
    1. Kalliomaki M., Collado M.C., Salminen S., Isolauri E. Early differences in fecal microbiota composition in children may predict overweight. Amer. J. Clin. Nutr. 2008;87:534–538.
    1. Payne A.N., Chassard C., Zimmermann M., Muller P., Stinca S., Lacroix C. The metabolic activity of gut microbiota in obese children is increased compared with normal-weight children and exhibits more exhaustive substrate utilization. Nutr. Diabetes. 2011;1 doi: 10.1038/nutd.2011.8.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe