Physical activity enhances the improvement of body mass index and metabolism by inulin: a multicenter randomized placebo-controlled trial performed in obese individuals.
Rodriguez, Julie; Neyrinck, Audrey M; Van Kerckhoven, Maximeet al.
Gut microbiota; Metabolism; Obesity; Physical activity; Prebiotic; Inulin; Animals; Body Mass Index; Diet, High-Fat; Exercise; Humans; Mice; Inulin/pharmacology; Obesity/drug therapy; Obesity/metabolism; Medicine (all); General Medicine
Abstract :
[en] ("[en] BACKGROUND: Dietary interventions targeting the gut microbiota have been proposed as innovative strategies to improve obesity-associated metabolic disorders. Increasing physical activity (PA) is considered as a key behavioral change for improving health. We have tested the hypothesis that changing the PA status during a nutritional intervention based on prebiotic supplementation can alter or even change the metabolic response to the prebiotic. We confirm in obese subjects and in high-fat diet fed mice that performing PA in parallel to a prebiotic supplementation is necessary to observe metabolic improvements upon inulin.
METHODS: A randomized, single-blinded, multicentric, placebo-controlled trial was conducted in obese participants who received 16 g/day native inulin versus maltodextrin, coupled to dietary advice to consume inulin-rich versus -poor vegetables for 3 months, respectively, in addition to dietary caloric restriction. Primary outcomes concern the changes on the gut microbiota composition, and secondary outcomes are related to the measures of anthropometric and metabolic parameters, as well as the evaluation of PA. Among the 106 patients who completed the study, 61 patients filled a questionnaire for PA before and after intervention (placebo: n = 31, prebiotic: n = 30). Except the dietitian (who provided dietary advices and recipes book), all participants and research staff were blinded to the treatments and no advices related to PA were given to participants in order to change their habits. In parallel, a preclinical study was designed combining both inulin supplementation and voluntary exercise in a model of diet-induced obesity in mice.
RESULTS: Obese subjects who increased PA during a 3 months intervention with inulin-enriched diet exhibited several clinical improvements such as reduced BMI (- 1.6 kg/m2), decreased liver enzymes and plasma cholesterol, and improved glucose tolerance. Interestingly, the regulations of Bifidobacterium, Dialister, and Catenibacterium genera by inulin were only significant when participants exercised more. In obese mice, we highlighted a greater gut fermentation of inulin and improved glucose homeostasis when PA is combined with prebiotics.
CONCLUSION: We conclude that PA level is an important determinant of the success of a dietary intervention targeting the gut microbiota.
TRIAL REGISTRATION: ClinicalTrials.gov, NCT03852069 (February 22, 2019 retrospectively registered).","[en] ","")
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Rodriguez, Julie; Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium
Neyrinck, Audrey M; Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium
Van Kerckhoven, Maxime; Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium
Gianfrancesco, Marco ; Université de Liège - ULiège > Département des sciences fonctionnelles (DSF) > Biochimie et biologie moléculaire
Renguet, Edith; Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium
Bertrand, Luc; Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium
Cani, Patrice D; Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium ; WELBIO- Walloon Excellence in Life Sciences and BIOtechnology, UCLouvain, Université catholique de Louvain, Brussels, Belgium
Lanthier, Nicolas; Laboratory of Hepatogastroenterology, Institut de Recherche Expérimentale et Clinique, UCLouvain, Université catholique de Louvain, Brussels, Belgium
Cnop, Miriam; ULB Center for Diabetes Research, Université Libre de Bruxelles, and Division of Endocrinology, Erasmus Hospital, Brussels, Belgium
Paquot, Nicolas ; Centre Hospitalier Universitaire de Liège - CHU > > Service de diabétologie, nutrition, maladies métaboliques
Thissen, Jean-Paul; Pole of Endocrinology, Diabetes and Nutrition, Institut de Recherche Expérimentale et Clinique, UCLouvain, Université catholique de Louvain, Brussels, Belgium
Bindels, Laure B; Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium
Delzenne, Nathalie M ; Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium. Nathalie.delzenne@uclouvain.be
Physical activity enhances the improvement of body mass index and metabolism by inulin: a multicenter randomized placebo-controlled trial performed in obese individuals.
This study was supported by the Service Public de Wallonie (SPW- EER, convention FOOD4GUT 1318148). NMD is a recipient of grants from the Fonds de la Recherche Scientifique (FRS-FNRS, Belgium, convention PDR T.0068.19 and convention PINT- MULTI R.8013.19 (NEURON, call 2019)) and from the Fédération Wallonie-Bruxelles (Action de Recherche Concertée ARC18-23/092).
Delzenne NM, Cani PD, Everard A, Neyrinck AM, Bindels LB. Gut microorganisms as promising targets for the management of type 2 diabetes. Diabetologia. 2015;58(10):2206–17.
Delzenne NM, Olivares M, Neyrinck AM, Beaumont M, Kjolbaek L, Larsen TM, et al. Nutritional interest of dietary fiber and prebiotics in obesity: lessons from the MyNewGut consortium. Clin Nutr. 2020;39(2):414–24.
Gibson GR, Hutkins R, Sanders ME, Prescott SL, Reimer RA, Salminen SJ, et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. 2017;14(8):491–502.
Cani PD, Possemiers S, Van de Wiele T, Guiot Y, Everard A, Rottier O, 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(8):1091–103.
Cani PD, Neyrinck AM, Fava F, Knauf C, Burcelin RG, Tuohy KM, et al. Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia. 2007;50(11):2374–83.
Everard A, Lazarevic V, Derrien M, Girard M, Muccioli GG, Neyrinck AM, et al. Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice. Diabetes. 2011;60(11):2775–86.
Weitkunat K, Stuhlmann C, Postel A, Rumberger S, Fankhanel M, Woting A, et al. Short-chain fatty acids and inulin, but not guar gum, prevent diet-induced obesity and insulin resistance through differential mechanisms in mice. Sci Rep. 2017;7(1):6109.
Dewulf EM, Cani PD, Neyrinck AM, Possemiers S, Van Holle A, Muccioli GG, et al. Inulin-type fructans with prebiotic properties counteract GPR43 overexpression and PPARgamma-related adipogenesis in the white adipose tissue of high-fat diet-fed mice. J Nutr Biochem. 2011;22(8):712–22.
Cani PD, Knauf C, Iglesias MA, Drucker DJ, Delzenne NM, Burcelin R. Improvement of glucose tolerance and hepatic insulin sensitivity by oligofructose requires a functional glucagon-like peptide 1 receptor. Diabetes. 2006;55(5):1484–90.
Hiel S, Neyrinck AM, Rodriguez J, Pachikian BD, Bouzin C, Thissen JP, et al. Inulin improves postprandial hypertriglyceridemia by modulating gene expression in the small intestine. Nutrients. 2018;10(5):532.
Weitkunat K, Schumann S, Petzke KJ, Blaut M, Loh G, Klaus S. Effects of dietary inulin on bacterial growth, short-chain fatty acid production and hepatic lipid metabolism in gnotobiotic mice. J Nutr Biochem. 2015;26(9):929–37.
Rodriguez J, Hiel S, Neyrinck AM, Le Roy T, Potgens SA, Leyrolle Q, et al. Discovery of the gut microbial signature driving the efficacy of prebiotic intervention in obese patients. Gut. 2020;69(11):1975–87.
Catry E, Bindels LB, Tailleux A, Lestavel S, Neyrinck AM, Goossens JF, et al. Targeting the gut microbiota with inulin-type fructans: preclinical demonstration of a novel approach in the management of endothelial dysfunction. Gut. 2018;67(2):271–83.
Cerdo T, Garcia-Santos JA, Bermúdez MG, Campoy C. The role of probiotics and prebiotics in the prevention and treatment of obesity. Nutrients. 2019;11(3):635.
Hiel S, Gianfrancesco MA, Rodriguez J, Portheault D, Leyrolle Q, Bindels LB, et al. Link between gut microbiota and health outcomes in inulin -treated obese patients: lessons from the Food4Gut multicenter randomized placebo-controlled trial. Clin Nutr. 2020;39(12):3618–28.
Dao MC, Everard A, Aron-Wisnewsky J, Sokolovska N, Prifti E, Verger EO, et al. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut. 2016;65(3):426–36.
Booth FW, Roberts CK, Laye MJ. Lack of exercise is a major cause of chronic diseases. Compr Physiol. 2012;2(2):1143–211.
Gabriel BM, Zierath JR. The limits of exercise physiology: from performance to health. Cell Metab. 2017;25(5):1000–11.
Barton W, Penney NC, Cronin O, Garcia-Perez I, Molloy MG, Holmes E, et al. The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level. Gut. 2018;67(4):625–33.
Clarke SF, Murphy EF, O'Sullivan O, Lucey AJ, Humphreys M, Hogan A, et al. Exercise and associated dietary extremes impact on gut microbial diversity. Gut. 2014;63(12):1913–20.
Allen JM, Mailing LJ, Niemiro GM, Moore R, Cook MD, White BA, et al. Exercise alters gut microbiota composition and function in lean and obese humans. Med Sci Sports Exerc. 2018;50(4):747–57.
Lambert JE, Myslicki JP, Bomhof MR, Belke DD, Shearer J, Reimer RA. Exercise training modifies gut microbiota in normal and diabetic mice. Appl Physiol Nutr Metab. 2015;40(7):749–52.
Evans CC, LePard KJ, Kwak JW, Stancukas MC, Laskowski S, Dougherty J, et al. Exercise prevents weight gain and alters the gut microbiota in a mouse model of high fat diet-induced obesity. PLoS One. 2014;9(3):e92193.
Campbell SC, Wisniewski PJ, Noji M, McGuinness LR, Haggblom MM, Lightfoot SA, et al. The effect of diet and exercise on intestinal integrity and microbial diversity in mice. PLoS One. 2016;11(3):e0150502.
Liu Y, Wang Y, Ni Y, Cheung CKY, Lam KSL, Wang Y, et al. Gut microbiome fermentation determines the efficacy of exercise for diabetes prevention. Cell Metab. 2020;31(1):77–91.e5.
Malkova D, Polyviou T, Rizou E, Gerasimidis K, Chambers ES, Preston T, et al. Moderate intensity exercise training combined with inulin-propionate ester supplementation increases whole body resting fat oxidation in overweight women. Metabolism. 2020;104:154043.
Food4Gut study - evaluation of the impact of prebiotics and prebiotic-enriched vegetables in obese patients. https://www.ncbi.nlm.nih.gov/bioproject/PRJNA595949/. Accessed 16 Dec 2019.
Schloss PD, Westcott SL, Ryabin T, Hall JR, Hartmann M, Hollister EB, et al. Introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities. Appl Environ Microbiol. 2009;75(23):7537–41.
Edgar RC. Accuracy of taxonomy prediction for 16S rRNA and fungal ITS sequences. PeerJ. 2018;6:e4652.
Wang Q, Garrity GM, Tiedje JM, Cole JR. Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy. Appl Environ Microbiol. 2007;73(16):5261–7.
Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods. 2010;7(5):335–6.
Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc. 1995;57:289–300.
Rios JL, Bomhof MR, Reimer RA, Hart DA, Collins KH, Herzog W. Protective effect of prebiotic and exercise intervention on knee health in a rat model of diet-induced obesity. Sci Rep. 2019;9(1):3893.
Rios JL, Hart DA, Reimer RA, Herzog W. Prebiotic and exercise do not alter knee osteoarthritis in a rat model of established obesity. Cartilage. 2020. https://doi.org/10.1177/1947603520959399.
Lanthier N, Rodriguez J, Nachit M, Hiel S, Trefois P, Neyrinck AM, et al. Microbiota analysis and transient elastography reveal new extra-hepatic components of liver steatosis and fibrosis in obese patients. Sci Rep. 2021;11(1):659.
Oh S, Tsujimoto T, Kim B, Uchida F, Suzuki H, Iizumi S, et al. Weight loss-independent benefits of exercise on liver steatosis and stiffness in Japanese men with NAFLD. JHEP reports; 2021. 10.1016/j.jhepr.2021.100253. DOI: 10.1016/j.jhepr.2021.100253
Matsumoto M, Inoue R, Tsukahara T, Ushida K, Chiji H, Matsubara N, et al. Voluntary running exercise alters microbiota composition and increases n-butyrate concentration in the rat cecum. Biosci Biotechnol Biochem. 2008;72(2):572–6.
Mika A, Van Treuren W, Gonzalez A, Herrera JJ, Knight R, Fleshner M. Exercise is more effective at altering gut microbial composition and producing stable changes in lean mass in juvenile versus adult male F344 rats. PLoS One. 2015;10(5):e0125889.
Petriz BA, Castro AP, Almeida JA, Gomes CP, Fernandes GR, Kruger RH, et al. Exercise induction of gut microbiota modifications in obese, non-obese and hypertensive rats. BMC Genomics. 2014;15:511.
Allen JM, Berg Miller ME, Pence BD, Whitlock K, Nehra V, Gaskins HR, et al. Voluntary and forced exercise differentially alters the gut microbiome in C57BL/6J mice. J Appl Physiol (1985). 2015;118(8):1059–66.
Lamoureux EV, Grandy SA, Langille MGI. Moderate exercise has limited but distinguishable effects on the mouse microbiome. mSystems. 2017;2(4):e00006–17.
Queipo-Ortuno MI, Seoane LM, Murri M, Pardo M, Gomez-Zumaquero JM, Cardona F, et al. Gut microbiota composition in male rat models under different nutritional status and physical activity and its association with serum leptin and ghrelin levels. PLoS One. 2013;8(5):e65465.
Zhang C, Li S, Yang L, Huang P, Li W, Wang S, et al. Structural modulation of gut microbiota in life-long calorie-restricted mice. Nat Commun. 2013;4:2163.
Peters HP, De Vries WR, Vanberge-Henegouwen GP, Akkermans LM. Potential benefits and hazards of physical activity and exercise on the gastrointestinal tract. Gut. 2001;48(3):435–9.
Salazar N, Dewulf EM, Neyrinck AM, Bindels LB, Cani PD, Mahillon J, et al. Inulin-type fructans modulate intestinal Bifidobacterium species populations and decrease fecal short-chain fatty acids in obese women. Clin Nutr. 2015;34(3):501–7.
Olivares M, Rodriguez J, Potgens SA, Neyrinck AM, Cani PD, Bindels LB, et al. The Janus face of cereals: wheat-derived prebiotics counteract the detrimental effect of gluten on metabolic homeostasis in mice fed a high-fat/high-sucrose diet. Mol Nutr Food Res. 2019;63(24):e1900632.
Li X, Guo J, Ji K, Zhang P. Bamboo shoot fiber prevents obesity in mice by modulating the gut microbiota. Sci Rep. 2016;6:32953.
Kovatcheva-Datchary P, Nilsson A, Akrami R, Lee YS, De Vadder F, Arora T, et al. Dietary fiber-induced improvement in glucose metabolism is associated with increased abundance of Prevotella. Cell Metab. 2015;22(6):971–82.
