Abstract
Objectives
Studies suggest that exercise affects the composition and function of the human gut microbiota, yet this has not been investigated in a randomized controlled trial. The primary aim of this study was to assess if exercise alters the diversity, composition and functional potential of the gut microbiota in free-living humans. A secondary aim was to test whether alpha diversity was associated with phenotypical outcomes.
Methods
Eighty eight participants with overweight or obesity completed a 6-month randomized controlled trial with 4 arms; habitual living (CON), active commuting by bike (BIKE) and leisure-time exercise of moderate (MOD) or vigorous intensity (VIG). Faecal samples for 16 s rRNA gene amplicon sequencing were collected prior to randomization and again after 3 and 6 months, with simultaneous registration of phenotypical outcomes and diet.
Results
Shannon’s diversity index increased by 5% in VIG (CI95 1–9%, P = 0.012) at 3 months compared with CON. No associations were observed between alpha diversity and phenotypical outcomes. Beta diversity changed in all exercise groups compared with CON, particularly the participants in VIG showed decreased heterogeneity. No genera changed significantly. The inferred functional potential of the microbiota in the exercise groups was increased, primarily at 3 months and in MOD.
Conclusion
Structured exercise induced subtle changes to the human gut microbiota. Cardiorespiratory fitness and fat mass were not associated with alpha diversity.
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References
Herrema H, IJzerman RG, Nieuwdorp M. Emerging role of intestinal microbiota and microbial metabolites in metabolic control. Diabetologia. 2017;60:613–7.
Janssen AWF, Kersten S. Potential mediators linking gut bacteria to metabolic health: a critical view. J Physiol. 2017;595:477–87.
Ussar S, Griffin NW, Bezy O, Fujisaka S, Vienberg S, Softic S, et al. Interactions between gut microbiota, host genetics and diet modulate the predisposition to obesity and metabolic syndrome. Cell Metab. 2015;22:516–30.
Le Chatelier E, Nielsen T, Qin J, Prifti E, Hildebrand F, Falony G, et al. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013;500:541–6.
Vrieze A, Van Nood E, Holleman F, Salojärvi J, Kootte RS, Bartelsman JFWM, et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012;143:913–6.e7.
Bäckhed F, Manchester JK, Semenkovich CF, Gordon JI. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci USA. 2007;104:979–84.
Most J, Goossens GH, Reijnders D, Canfora EE, Penders J, Blaak EE. Gut microbiota composition strongly correlates to peripheral insulin sensitivity in obese men but not in women. Benef Microbes. 2017;8:557–62.
Bonder MJ, Kurilshikov A, Tigchelaar EF, Mujagic Z, Imhann F, Vila AV, et al. The effect of host genetics on the gut microbiome. Nat Genet. 2016;48:1407–12.
Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R. Diversity, stability and resilience of the human gut microbiota. Nature. 2012;489:220–30.
David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505:559–63.
Wu H, Esteve E, Tremaroli V, Khan MT, Caesar R, Mannerås-Holm L, et al. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nat Med. 2017;23:850–8.
Maier L, Pruteanu M, Kuhn M, Zeller G, Telzerow A, Anderson EE, et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature. 2018;555:623–8.
Bird SR, Hawley JA. Update on the effects of physical activity on insulin sensitivity in humans. BMJ Open Sport Exerc Med. 2017;2:e000143.
Verheggen RJHM, Maessen MFH, Green DJ, Hermus ARMM, Hopman MTE, Thijssen DHT. A systematic review and meta-analysis on the effects of exercise training versus hypocaloric diet: distinct effects on body weight and visceral adipose tissue. Obes Rev. 2016;17:664–90.
Lin X, Zhang X, Guo J, Roberts CK, McKenzie S, Wu W-C, et al. Effects of exercise training on cardiorespiratory fitness and biomarkers of cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials. J Am Heart Assoc. 2015;1–29.
Durstine JL, Gordon B, Wang Z, Luo X. Chronic disease and the link to physical activity. J Sport Heal Sci. 2013;2:3–11.
Richter EA, Hargreaves M. Exercise, GLUT4, and Skeletal Muscle Glucose Uptake. Physiol Rev. 2013;93:993–1017.
Beaulieu K, Hopkins M, Blundell J, Finlayson G. Homeostatic and non-homeostatic appetite control along the spectrum of physical activity levels: an updated perspective. Physiol Behav. 2018;192:23–9.
Campbell SC, Wisniewski PJ, Noji M, McGuinness LR, Häggblom MM, Lightfoot SA, et al. The effect of diet and exercise on intestinal integrity and microbial diversity in mice. PLoS ONE. 2016;11:1–17.
Cook MD, Allen JM, Pence BD, Wallig MA, Gaskins HR, White BA, et al. Exercise and gut immune function: evidence of alterations in colon immune cell homeostasis and microbiome characteristics with exercise training. Immunol Cell Biol. 2016;94:158–63.
Cerdá B, Pérez M, Pérez-Santiago JD, Tornero-Aguilera JF, González-Soltero R, Larrosa M. Gut microbiota modification: another piece in the puzzle of the benefits of physical exercise in health? Front Physiol. 2016;7:51.
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.
Queipo-Ortuño 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:e65465.
Kang SS, Jeraldo PR, Kurti A, Miller MEB, Cook MD, Whitlock K, et al. Diet and exercise orthogonally alter the gut microbiome and reveal independent associations with anxiety and cognition. Mol Neurodegener. 2014;9:1–12.
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. 2015;118:1059–66.
Welly RJ, Liu TW, Zidon TM, Rowles JL, Park YM, Smith TN, et al. Comparison of diet versus exercise on metabolic function and gut microbiota in obese rats. Med Sci Sports Exerc. 2016;48:1688–98.
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;67:625–33.
Estaki M, Pither J, Baumeister P, Little JP, Gill SK, Ghosh S, et al. Cardiorespiratory fitness as a predictor of intestinal microbial diversity and distinct metagenomic functions. Microbiome. 2016;4:1–13.
Bressa C, Bailén-Andrino M, Pérez-Santiago J, González-Soltero R, Pérez M, Montalvo-Lominchar MG, et al. Differences in gut microbiota profile between women with active lifestyle and sedentary women. PLoS ONE. 2017;12:e0171352.
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;63:1913–20.
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;50:747–57.
Munukka E, Ahtiainen JP, Puigbó P, Jalkanen S, Pahkala K, Keskitalo A, et al. Six-week endurance exercise alters gut metagenome that is not reflected in systemic metabolism in over-weight women. Front Microbiol. 2018;9:2323.
Cronin O, Barton W, Skuse P, Penney NC, Garcia-Perez I, Murphy EF, et al. A prospective metagenomic and metabolomic analysis of the impact of exercise and/or whey protein supplementation on the gut microbiome of sedentary adults. mSystems. 2018;3:1–17.
Cronin O, O’Sullivan O, Barton W, Cotter PD, Molloy MG, Shanahan F. Gut microbiota: implications for sports and exercise medicine. Br J Sports Med. 2017;51:700–1.
Ross R, Hudson R, Stotz PJ, Lam M. Effects of exercise amount and intensity on abdominal obesity and glucose tolerance in obese adults. Ann Intern Med. 2015;162:325.
Slentz CA, Aiken LB, Houmard JA, Bales CW, Johnson JL, Tanner CJ, et al. Role of exercise in reducing the risk of diabetes and obesity inactivity, exercise, and visceral fat. STRRIDE: a randomized, controlled study of exercise intensity and amount. J Appl Physiol. 2005;99:1613–8.
Houmard JA, Tanner CJ, Slentz CA, Duscha BD, McCartney JS, Kraus WE. Effect of the volume and intensity of exercise training on insulin sensitivity. J Appl Physiol. 2004;96:101–6.
Rosenkilde M, Petersen MB, Gram AS, Quist JS, Winther J, Kamronn SD, et al. The GO-ACTIWE randomized controlled trial - an interdisciplinary study designed to investigate the health effects of active commuting and leisure time physical activity. Contemp Clin Trials. 2017;53:122–9.
Quist JS, Rosenkilde M, Petersen MB, Gram AS, Sjödin A, Stallknecht B. Effects of active commuting and leisure-time exercise on fat loss in women and men with overweight and obesity: a randomized controlled trial. Int J Obes. 2018;42:469–78.
Caporaso JG, Lauber CL, Walters WA, Berg-Lyons D, Huntley J, Fierer N, et al. Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms. ISME J. 2012;6:1621–4.
Kozich JJ, Westcott SL, Baxter NT, Highlander SK, Schloss PD. Development of a dual-index sequencing strategy and curation pipeline for analyzing amplicon sequence data on the MiSeq Illumina sequencing platform. Appl Environ Microbiol. 2013;79:5112–20.
Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJA, Holmes SP. DADA2: high-resolution sample inference from Illumina amplicon data. Nat Methods. 2016;13:581–3.
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;73:5261–7.
Schliep KP. Phangorn: phylogenetic analysis in R. Bioinformatics. 2011;27:592–3.
McMurdie PJ, Holmes S, Kindt R, Legendre P, O’Hara R. Phyloseq: an R Package for reproducible interactive analysis and graphics of microbiome census data. PLoS ONE. 2013;8:e61217.
Iwai S, Weinmaier T, Schmidt BL, Albertson DG, Poloso NJ, Dabbagh K, et al. Piphillin: improved prediction of metagenomic content by direct inference from human microbiomes. PLoS ONE. 2016;11:e0166104.
Vieira-Silva S, Falony G, Darzi Y, Lima-Mendez G, Garcia Yunta R, Okuda S, et al. Species-function relationships shape ecological properties of the human gut microbiome. Nat Microbiol. 2016;1:1–8.
Benjamini Y, Hochberg Y, Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc B. 1995;57:289–300.
McArdle BH, Anderson MJ. Fitting multivariate models to community data: a comment on distance‐based redundancy analysis. Ecology. 2001;82:290–7.
Anderson MJ, Ellingsen KE, McArdle BH. Multivariate dispersion as a measure of beta diversity. Ecol Lett. 2006;9:683–93.
Warton DI, Wright ST, Wang Y. Distance-based multivariate analyses confound location and dispersion effects. Methods Ecol Evol. 2012;3:89–101.
Menni C, Jackson MA, Pallister T, Steves CJ, Spector TD, Valdes AM. Gut microbiome diversity and high-fibre intake are related to lower long-term weight gain. Int J Obes. 2017;41:1099–105.
Cotillard A, Kennedy SP, Kong LC, Prifti E, Pons N, Le Chatelier E, et al. Dietary intervention impact on gut microbial gene richness. Nature. 2013;500:585–8.
Acknowledgements
We would like to thank all participants, as well as the technical staff and the students in our lab; in particular we would like to thank Desirée Milling for her invaluable work. Furthermore, we thank Asker Daniel Brejnrod, Christian Theil Have, and Manimozhiyan Arumugam for their assistance and important advice in relation to the microbiome analysis.
Author contributions
TK and MBB contributed equally to this paper. MBB, MR, JSQ, ASG, TH and BS: conception and design of the study. TK, MBB, MR, JSQ, ASG and BS: acquisition of data. TK, MBB, THH and CTE: analysis and interpretation of data. TK and MBB: drafting the manuscript. TK, MBB, THH, MR, JSQ, ASG, CTE, BS and TH: revision of the manuscript. All authors read and approved the final version of the manuscript.
Funding
The work is carried out as a part of the research programme ‘Governing Obesity’ funded by the University of Copenhagen's Excellence Programme for Interdisciplinary Research (http://go.ku.dk/). Additional funding was provided by the Faculty of Health and Medical Sciences, University of Copenhagen, TrygFonden and Gerda og Aage Haenschs Fond.
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The study was approved by the ethical committee of The Capital Region of Denmark (H-4-2013-108), and is registered at clinicaltrials.gov (NCT01962259) and at the Danish Data Protection Agency. The study was performed in accordance with the Helsinki declaration.
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Kern, T., Blond, M.B., Hansen, T.H. et al. Structured exercise alters the gut microbiota in humans with overweight and obesity—A randomized controlled trial. Int J Obes 44, 125–135 (2020). https://doi.org/10.1038/s41366-019-0440-y
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DOI: https://doi.org/10.1038/s41366-019-0440-y
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