Effects of short-term exercise training on intestinal metabolism and gut microbiota

Transcription

1 Effects of short-term exercise training on intestinal metabolism and gut microbiota Kumail K. Motiani M. Carmen Collado, Joonas J. Eskelinen, Kirsi A. Virtanen, Eliisa Löyttyniemi, Seppo Salminen, Pirjo Nuutila, Kari K. Kalliokoski, Jarna C. Hannukainen XVI National Diabetes Day

2 Presenter Disclosure Information Kumail K. Motiani Disclosed no conflict of interest

3 BACKGROUND Intestine Small intestine Large intestine Main functions Major site for absorption of carbohydrates, fat and proteins Main functions Absorption of water and vitamins

4 INTESTINE IS INSULIN SENSITIVE ORGAN Healthy Obese Before surgery Obese After bariatric surgery * % % Honka et al. Diabetologia 2013 Mäkinen et al. Diabetologia 2015

5 BACKGROUND Importance of gut microbiota Altered gut microbiota Brain Satiety Liver Short chain fatty acids Inflammation Adipose tissue Triglyceride incorporation Inflammation Muscle Fatty acid oxidation Grenham Sue et al Front. Physio. 2:940 Epithelium Permeability of the epithelium Valentina Tremaroli & Fredrik Bäckhed Nature489,

6 BACKGROUND Diabetes Mellitus Body fat percentage Aerobic fitness Coronary artery disease Insulin sensitivity Hypertension Circulation Weight Inflammation Oxidative stress Muscle metabolism

7 BACKGROUND Diabetes Mellitus Body fat percentage Aerobic fitness Coronary artery disease Insulin sensitivity Effects Hypertension of exercise on intestine? - Intestinal substrate uptake - On gut microboita Weight Circulation Inflammation Oxidative stress Muscle metabolism

8 BACKGROUND SIT improves exercise capacity Sprint interval training (SIT) n = 14 CON SIT Burgomaster et al. J Appl Physiol 2005 Moderate intensity continuous training (MICT) n = 14 SIT improves muscle insulin sensitivity Marja A. Heiskanen et al. Am J Physiol Heart Circ Physiol 2016 SIT (sprint interval training) MICT (moderate intensity continuous training) SIT MICT Eskelinen et al. J Appl Physiol 2015

9 AIMS Our aims were to study the effects of two weeks of exercise training 1. on the intestinal metabolism in both healthy and insulin resistant subjects, 2. to measure the effects on the intestinal gut microbiota and 3. whether these potential improvements are dependent of training mode and intensity.

10 DESIGN NCT Insulin resistant study subjects T2D IFG/IGT N Male/Female 11/5 5/5 Age (y) 47[46,49] 52[50,53] Glucose lowering medication Metformin 11 DPP-4 inhibitors (sitagliptin) Sulfonylurea (glimepiride) 5 1

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12 EXERCISE-INDUCED CHANGES BY GROUPS Anthropometrics Healthy P values IFG/IGT/T2D P values SIT Pre SIT Δ % Data shown is model based mean and 95% confidence intervals (CI) Log transformation was done to achieve normal distribution MICT Pre MICT Δ % Time Training* Time N SIT Pre SIT Δ % MICT Pre MICT Δ % Time Training* Time BMI (kg/m 2 ) 25.9 [24.5; 27.3] 26.4 [25.0; 27.7] [28;32] 31.0 [29;33] Whole body fat (%) Subcutaneous Fat (kg) 22.2 [19.8; 24.6] [20.5; 25.3] -3 < [28;38] [26;36] [3.3; 4.8] [3.7; 5.2] [5.7;8.8] [5.7;8.7] Visceral Fat (kg) 2.9 [2.1;3.8] [1.8; 3.5] [2.3;4.1] [2.7;4.7] Glucose Profile Glucose fasting (mmol/l) Insulin fasting (mu/l) HBA1c (mmol/mol) 5.5 [5.3; 7.4] 5.7 [5.5; 5.9] [6.4;7.4] 6.5 [6.0;6.9] [3.8; 7.2] 5.8 [4.1; 8.1] [8.4;18.8] 9.5 [6.6;13.7] [34.3; 38.6] [35.3; 39.5] -9 < [37;42] [37;42] Lipid Profile FFA fasting (mmol/l) 0.61 [0.50;0.71] 0.78 [0.7; 0.9] [0.6;0.9] 0.84[0.7;1.0] Cholesterol (mmol/l) 5.3 [4.8;5.7] [4.3;5.2] -8 < [4.2;5.2] [4.4;5.6] HDL (mmol/l) 1.4 [1.2;1.6] [1.2;1.5] -5 < [1.1;1.5] [1.1;1.6] LDL (mmol/l) 3.4 [3.0; 3.8] [2.5;3.5] -6 < [2.2;3.0] [2.5;3.5] Triglycerides (mmol/l) 1.0 [0.8; 1.1] 1.0 [0.8;1.1] [1.1;2.0] 1.53 [1.1;2.1]

13 EXERCISE TRAINING IMPROVED AEROBIC CAPACITY AND WHOLE BODY INSULIN SENSITIVITY Healthy IFG/IGT/T2D SIT (sprint interval training) MICT (moderate intensity continuous training) * p value for training effect over time, but no difference between the training modes. p value for time*training effect, differences between the training modes

14 Fasting free fatty acid uptake Fasting free fatty acid uptake Insulin stimulated glucose uptake Insulin stimulated glucose uptake INTESTINAL METABOLISM Healthy IFG/IGT/T2D * * * # Figures presented are model based mean and 95% confidence intervals (CI). *p<0.05, Time effect; #p=0.08; Time*training effect Motiani KK et al J Appl Physiol 2017 *P = 0.046; Time* Training

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16 Relative abundance (%) EXERCISE IMPROVED FIRMICUTES/BACTEROIDETES RATIO Weight loss improves F/B ratio Obese Before After Clinical importance F/B ratio has a significant relevance in the gut microbiota composition F/B ratio in obese subjects F/B ratio in lean subjects and after weight loss Mariat D et al BMC Microbiology 2009

17 Relative abundance (%) EXERCISE INCREASED BACTEROIDES Before exercise Before After Clinical importance Perform metabolic conversions essential to the host in obesity, irritable bowel syndrome Rajilic-Stojanovic M and M. de Voc W. FEMS Microbiol 2014

18 Relative abundance (%) EXERCISE DECREASED BLAUTIA Before exercise Before After Clinical importance Suggested to activate the release of pro inflammatory markers (TNFα, Cytokines) Blautia in Type 1 and Type 2 diabetics. Touvinen et al 2013, Egshatyan et al 2016 Endocr connect and Kostic et al 2015 CellHost and Microbe

19 Relative abundance (%) EXERCISE DECREASED DOREA Before exercise Before After Clinical importance Major gas producers in patients with irritable bowel syndrome Rajilic-Stojanovic M and M. de Voc W. FEMS Microbiol 2014

20 CONCLUSIONS Our study suggests that Already two weeks of moderate intensity exercise training increases the insulin stimulated glucose uptake in healthy and decreases the fasting free fatty acid uptake both in healthy and diabetic subjects Gut microbiota composition associates with insulin-stimulated intestinal glucose uptake Exercise training (both SIT and MICT) improves gut microbiota profile

21 Thank you!!!! University of Turku Turku PET Centre Hannukainen Jarna Kalliokoski Kari Nuutila Pirjo Virtanen Kirsi Eskelinen Joonas Koivumäki Mikko Löyttyniemi Eliisa EMIL AALTONEN FOUNDATION Functional Food Forum Salminen Seppo IATA-CSIC Spain M.Carmen Collado Correspondance