Six-Week Exercise Training With Dietary Restriction Improves Central Hemodynamics Associated With Altered Gut Microbiota in Adolescents With Obesity

Junhao Huang, Jingwen Liao, Yang Fang, Hailin Deng, Honggang Yin, Bing Shen, Min Hu, Junhao Huang, Jingwen Liao, Yang Fang, Hailin Deng, Honggang Yin, Bing Shen, Min Hu

Abstract

Purpose: Obesity in children and in adolescents can lead to adult cardiovascular diseases, and the gut microbiota plays a crucial role in obesity pathophysiology. Exercise and diet interventions are typical approaches to improve physical condition and to alter the gut microbiota in individuals with obesity. However, whether central hemodynamic parameters including subendocardial viability ratio, the augmentation index standardized to a heart rate of 75/min (AIx75), resting heart rate, and blood pressure, correlate with gut microbiota changes associated with exercise and diet is unclear.

Methods: Adolescents (n = 24, 12.88 ± 0.41 years) with obesity completed our 6-week program of endurance and strength exercises along with dietary restriction. Blood and fecal samples were collected, and physical parameters were measured before and 24 h after the last session of the intervention program. Pulse wave analysis using applanation tonometry provided the subendocardial viability ratio, a surrogate measure of microvascular myocardial perfusion, and AIx75, a measure of arterial stiffness and peripheral arteriolar resistance. Correlation analysis detected any associations of anthropometric or central hemodynamic parameters with gut microbiome composition.

Results: Exercise and diet interventions significantly reduced body weight, body mass index, body fat, and waist-to-hip ratio, and lowered levels of fasting blood glucose, serum triglycerides, and high-density lipoprotein cholesterol. AIx75 and resting heart rate were also significantly reduced after the intervention without changes to systolic or diastolic blood pressure. The ratio of intestinal microbiota Firmicutes to Bacteroidetes displayed a marked increase after intervention. Interventional changes in gut microbiota members were significantly associated with anthropometric and metabolic parameters. Microbial changes were also significantly correlated with central hemodynamic parameters, including subendocardial viability ratio, AIx75, and resting heart rate.

Conclusion: Exercise and diet interventions significantly improved measures of central hemodynamics, including subendocardial viability ratio, AIx75, and resting heart rate, which were correlated with altered gut microbiota in adolescents with obesity. Our findings shed light on the effects and mechanisms underlying exercise and diet interventions on obesity and suggest this approach for treating patients with both cardiovascular disease and obesity.

Trial registration: ClinicalTrials.gov NCT03762629.

Keywords: dietary restriction; exercise; gut microflora; obese adolescents; subendocardial viability ratio.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2020 Huang, Liao, Fang, Deng, Yin, Shen and Hu.

Figures

Figure 1
Figure 1
Characteristics of two microbiota. (A) Venn diagram. The Venn diagram shows the unique operational taxonomic units (OTUs) pre-intervention (Before; brown) and post-intervention (After; light-red), and the number of shared OTUs (dark-red) pre- and post-intervention. (B) OTU rank abundance curves. The legend indicates the Sample Number. Before presents pre-intervention. After presents post-intervention. (C) Species accumulation boxplot of the 48 samples.
Figure 2
Figure 2
The taxonomic composition distribution in samples at the phylum level. The abscissa represents the Sample Number. Before presents pre-intervention, After presents post-intervention. The 48 samples are divided into two parts. The blue part is from After1 to After24, and the red part is from Before1 to Before24. The legend in the upper right corner represents the name of the species at the phylum level. The content of the bacteria is displayed in the histogram in the corresponding proportion and color.
Figure 3
Figure 3
Linear discriminant analysis effect size before and after diet and exercise intervention. (A) Cladogram of the gastric microbial taxa associated with individuals before and after diet and exercise intervention. Taxa higher in relative abundance before the intervention are in green, and those higher after the intervention are in red. (B) Histogram of the linear discriminant analysis (LDA) scores for differentially abundant taxonomic features before and after the intervention. Significance obtained by LDA effect size at P < 0.05, (Kruskal–Wallis test) and LDA score >2.
Figure 4
Figure 4
Correlation network between changes in gut microbiota members and clinical parameters after a 6-week combined exercise and diet intervention. (A) Correlations between changes in gut microbiota members and metabolic parameters. (B) Correlations between changes in gut microbiota members and central hemodynamics. The blue square represents clinical parameters, the red circle represents gut microbiota; the red line represents the positive correlation coefficient, and the green line represents the negative correlation coefficient.

References

    1. Gungor NK. Overweight and obesity in children and adolescents. J Clin Res Pediatr Endocrinol (2014) 6:129–43.
    1. Acree LS, Comp PC, Whitsett TL, Montgomery PS, Nickel KJ, Fjeldstad AS, et al. The influence of obesity on calf blood flow and vascular reactivity in older adults. Dynamic Med: DM (2007) 6:4.
    1. Wang Y, Kuang Z, Yu X, Ruhn KA, Kubo M, Hooper LV. The intestinal microbiota regulates body composition through NFIL3 and the circadian clock. Science (2017) 357:912–6.
    1. Gerard P. Gut microbiota and obesity. Cell Mol Life Sci: CMLS (2016) 73:147–62.
    1. Ley RE, Backhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI. Obesity alters gut microbial ecology. Proc Natl Acad Sci USA (2005) 102:11070–5.
    1. Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature (2006) 444:1022–3.
    1. Bruyndonckx L, Hoymans VY, De Guchtenaere A, Van Helvoirt M, Van Craenenbroeck EM, Frederix G, et al. Diet, exercise, and endothelial function in obese adolescents. Pediatrics (2015) 135:e653–61.
    1. Goldberg Y, Boaz M, Matas Z, Goldberg I, Shargorodsky M. Weight loss induced by nutritional and exercise intervention decreases arterial stiffness in obese subjects. Clin Nutr (2009) 28:21–5.
    1. Woo KS, Chook P, Yu CW, Sung RY, Qiao M, Leung SS, et al. Effects of diet and exercise on obesity-related vascular dysfunction in children. Circulation (2004) 109:1981–6.
    1. Kim B, Choi HN, Yim JE. Effect of Diet on the Gut Microbiota Associated with Obesity. J Obes Metab Syndrome (2019) 28:216–24.
    1. Sergeev IN, Aljutaily T, Walton G, Huarte E. Effects of Synbiotic Supplement on Human Gut Microbiota, Body Composition and Weight Loss in Obesity. Nutrients (2020) 12(1):222.
    1. 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 Exercise (2018) 50:747–57.
    1. Kern T, Blond MB, Hansen TH, Rosenkilde M, Quist JS, Gram AS, et al. Structured exercise alters the gut microbiota in humans with overweight and obesity-A randomized controlled trial. Int J Obes (2020) 44:125–35.
    1. Menni C, Lin C, Cecelja M, Mangino M, Matey-Hernandez ML, Keehn L, et al. Gut microbial diversity is associated with lower arterial stiffness in women. Eur Heart J (2018) 39:2390–7.
    1. Group of China Obesity Task F [Body mass index reference norm for screening overweight and obesity in Chinese children and adolescents]. Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi (2004) 25:97–102.
    1. Huang J, Lai Q, Wang D, Yin H, Liao J, Wang S, et al. Effects Of Exercise Training With Dietary Restriction On Arterial Stiffness, Central Hemodynamic Parameters And Cardiac Autonomic Function In Obese Adolescents. Diabetes Metab Syndrome Obes: Targets Ther (2019) 12:2157–63.
    1. Huang J, Wang S, Xu F, Wang D, Yin H, Lai Q, et al. Exercise training with dietary restriction enhances circulating irisin level associated with increasing endothelial progenitor cell number in obese adults: an intervention study. PeerJ (2017) 5:e3669.
    1. Xiang MQ, Liao JW, Huang JH, Deng HL, Wang D, Xu Z, et al. Effect of a Combined Exercise and Dietary Intervention on Self-Control in Obese Adolescents. Front Psychol (2019) 10:1385.
    1. Wang R, Chen P, Chen W. Effect of Diet and Exercise-induced Weight Reduction on Complement Regulatory Proteins CD55 and CD59 Levels in Overweight Chinese Adolescents. J Exercise Sci Fitness (2011) 9:46–51.
    1. Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science (2011) 334:105–8.
    1. Magoc T, Salzberg SL. FLASH: fast length adjustment of short reads to improve genome assemblies. Bioinformatics (2011) 27:2957–63.
    1. Rognes T, Flouri T, Nichols B, Quince C, Mahe F. VSEARCH: a versatile open source tool for metagenomics. PeerJ (2016) 4:e2584.
    1. 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.
    1. Quast C, Pruesse E, Yilmaz P, Gerken J, Schweer T, Yarza P, et al. The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic Acids Res (2013) 41:D590–6.
    1. DeSantis TZ, Hugenholtz P, Larsen N, Rojas M, Brodie EL, Keller K, et al. Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB. Appl Environ Microbiol (2006) 72:5069–72.
    1. Abarenkov K, Henrik Nilsson R, Larsson KH, Alexander IJ, Eberhardt U, Erland S, et al. The UNITE database for molecular identification of fungi–recent updates and future perspectives. New Phytol (2010) 186:281–5.
    1. 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) 7:335–6.
    1. Nirmalkar K, Murugesan S, Pizano-Zarate ML, Villalobos-Flores LE, Garcia-Gonzalez C, Morales-Hernandez RM, et al. Gut Microbiota and Endothelial Dysfunction Markers in Obese Mexican Children and Adolescents. Nutrients (2018) 10(12):2009.
    1. Ekart R, Bevc S, Hojs N, Hojs R. Derived Subendocardial Viability Ratio and Cardiovascular Events in Patients with Chronic Kidney Disease. Cardiorenal Med (2019) 9:41–50.
    1. Sandoo A, Protogerou AD, Hodson J, Smith JP, Zampeli E, Sfikakis PP, et al. The role of inflammation, the autonomic nervous system and classical cardiovascular disease risk factors on subendocardial viability ratio in patients with RA: a cross-sectional and longitudinal study. Arthritis Res Ther (2012) 14:R258.
    1. Kuznetsova TY, Korneva VA, Bryantseva EN, Barkan VS, Orlov AV, Posokhov IN, et al. The 24-hour pulse wave velocity, aortic augmentation index, and central blood pressure in normotensive volunteers. Vasc Health Risk Manage (2014) 10:247–51.
    1. Gielen S, Schuler G, Adams V. Cardiovascular effects of exercise training: molecular mechanisms. Circulation (2010) 122:1221–38.
    1. Van Guilder GP, Hoetzer GL, Dengel DR, Stauffer BL, DeSouza CA. Impaired endothelium-dependent vasodilation in normotensive and normoglycemic obese adult humans. J Cardiovasc Pharmacol (2006) 47:310–3.
    1. Doonan RJ, Scheffler P, Yu A, Egiziano G, Mutter A, Bacon S, et al. Altered arterial stiffness and subendocardial viability ratio in young healthy light smokers after acute exercise. PLoS One (2011) 6:e26151.
    1. Laugesen E, Hoyem P, Fleischer J, Kumarathas I, Knudsen ST, Hansen KW, et al. Reduced Subendocardial Viability Ratio Is Associated With Unfavorable Cardiovascular Risk Profile in Women With Short Duration of Type 2 Diabetes. Am J Hypertension (2016) 29:1165–72.
    1. Di Micco L, Salvi P, Bellasi A, Sirico ML, Di Iorio B. Subendocardial viability ratio predicts cardiovascular mortality in chronic kidney disease patients. Blood Purification (2013) 36:26–8.
    1. Zaniqueli D, Alvim RO, Baldo MP, Luiz SG, Cunha RS, Mill JG. Excess weight in children and adolescents is associated with altered subendocardial blood supply among girls but not boys. Clin Exp Pharmacol Physiol (2018) 45:471–4.
    1. Franssen WMA, Beyens M, Hatawe TA, Frederix I, Verboven K, Dendale P, et al. Cardiac function in adolescents with obesity: cardiometabolic risk factors and impact on physical fitness. Int J Obes (2019) 43:1400–10.
    1. Hoffman RP, Copenhaver MM, Zhou D, Yu CY. Increased body fat and reduced insulin sensitivity are associated with impaired endothelial function and subendocardial viability in healthy, non-Hispanic white adolescents. Pediatr Diabetes (2019) 20:842–8.
    1. Tremaroli V, Backhed F. Functional interactions between the gut microbiota and host metabolism. Nature (2012) 489:242–9.
    1. Jia Q, Li H, Zhou H, Zhang X, Zhang A, Xie Y, et al. Role and Effective Therapeutic Target of Gut Microbiota in Heart Failure. Cardiovasc Ther (2019) 2019:5164298.
    1. Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, et al. A core gut microbiome in obese and lean twins. Nature (2009) 457:480–4.
    1. Fernandes J, Su W, Rahat-Rozenbloom S, Wolever TM, Comelli EM. Adiposity, gut microbiota and faecal short chain fatty acids are linked in adult humans. Nutr Diabetes (2014) 4:e121.
    1. Salah M, Azab M, Ramadan A, Hanora A. New Insights on Obesity and Diabetes from Gut Microbiome Alterations in Egyptian Adults. Omics: J Integr Biol (2019) 23:477–85.
    1. Magne F, Gotteland M, Gauthier L, Zazueta A, Pesoa S, Navarrete P, et al. The Firmicutes/Bacteroidetes Ratio: A Relevant Marker of Gut Dysbiosis in Obese Patients? Nutrients (2020) 12(5):1474.
    1. Li X, Li C. Analysis of changes in intestinal flora and intravascular inflammation and coronary heart disease in obese patients. Exp Ther Med (2018) 15:4538–42.
    1. Yang T, Santisteban MM, Rodriguez V, Li E, Ahmari N, Carvajal JM, et al. Gut dysbiosis is linked to hypertension. Hypertension (2015) 65:1331–40.
    1. Munukka E, Ahtiainen JP, Puigbo 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.
    1. Goodrich JK, Waters JL, Poole AC, Sutter JL, Koren O, Blekhman R, et al. Human genetics shape the gut microbiome. Cell (2014) 159:789–99.
    1. Waters JL, Ley RE. The human gut bacteria Christensenellaceae are widespread, heritable, and associated with health. BMC Biol (2019) 17:83.
    1. Peters BA, Shapiro JA, Church TR, Miller G, Trinh-Shevrin C, Yuen E, et al. A taxonomic signature of obesity in a large study of American adults. Sci Rep (2018) 8:9749.
    1. Battson ML, Lee DM, Li Puma LC, Ecton KE, Thomas KN, Febvre HP, et al. Gut microbiota regulates cardiac ischemic tolerance and aortic stiffness in obesity. Am J Physiol Heart Circulatory Physiol (2019) 317:H1210–H20.
    1. Gu Y, Liu C, Zheng N, Jia W, Zhang W, Li H. Metabolic and Gut Microbial Characterization of Obesity-Prone Mice under a High-Fat Diet. J Proteome Res (2019) 18:1703–14.
    1. Hu M, Wang S, Wang D, Lai Q, Chen X, Duan S, et al. Combined moderate and high intensity exercise with dietary restriction improves cardiac autonomic function associated with a reduction in central and systemic arterial stiffness in obese adults: a clinical trial. PeerJ (2017) 5:e3900.
    1. Gately PJ, Cooke CB, Butterly RJ, Mackreth P, Carroll S. The effects of a children’s summer camp programme on weight loss, with a 10 month follow-up. Int J Obes Rel Metab Disorders: J Int Assoc Study Obes (2000) 24:1445–52.

Source: PubMed

3
Tilaa