Effects of a combined energy restriction and vigorous intensity exercise intervention on the human gut microbiome – a randomised controlled trial. The effect of an energy deficit on the gut microbiome

Metabolic health improvements in response to exercise and energy restriction may be mediated by the gut microbiome, yet causal evidence in humans remains limited. We used a 3-week exercise and energy restriction intervention to examine changes to the gut microbiome in otherwise healthy sedentary men and postmenopausal women with overweight/obesity. Intervention participants (n=18) were instructed to reduce habitual energy intake by 5000 kcal/week and expend 2000 kcal/week in addition to habitual physical activity through treadmill walking at 70% V̇O2Peak. Control participants (n=12) were instructed to maintain their usual lifestyle. Participants underwent dual X-ray absorptiometry (DEXA) and samples of faeces and fasted blood were collected. Faecal DNA was sequenced and profiled using shotgun metagenomics, Kraken2/Bracken and HUMAnN2. The intervention (relative to control) significantly reduced body mass (mean change ± SD Δ -2.6 ± 1.5 kg vs. +0.6 ± 0.8 kg, p<0.01), fat mass (Δ -1.5 ± 1.3 kg vs. +0.2 ± 1.0 kg, p<0.01), insulin (Δ -23.5 ± 38.1 pmol/L vs. +4.21 ± 24.1 pmol/L, p=0.03), leptin (Δ -10.6 ± 7.3 ng/mL vs. -1.9 ± 6.4 ng/mL, p<0.01), and total cholesterol (Δ -0.7 ± 0.4 mmol/L vs. -0.1 ± 0.4 mmol/L, p<0.01), with improved insulin sensitivity (iHOMA2%S; Δ +43.0 ± 49.0 vs. +9.7 ± 37.0, p=0.02). Despite significant metabolic changes, the gut microbiome was unchanged in terms of alpha and beta diversity and relative abundance. In conclusion, despite clinically meaningful changes in body composition and metabolic health, we found no evidence that changes to the gut microbiome were required.