A randomized controlled trial for response of microbiome network to exercise and diet intervention in patients with nonalcoholic fatty liver disease.

Nature communications. 2022;13(1):2555

Plain language summary

Non-alcoholic fatty liver disease (NAFLD) is a common chronic disease that is associated with the development of type 2 diabetes (T2D). A commonality between the two diseases is the body’s inefficiency to uptake sugar from the blood, known as insulin resistance. Dysbiosis of the gut microbiota has been shown to be involved in NAFLD and T2D. Exercise and dietary modifications have been shown to increase gut microbiota diversity altering the composition, however the extent of this change is poorly understood. This randomised control trial of 115 individuals with NAFLD and insulin resistance aimed to determine the effects of aerobic exercise and a diet comprising of 37-40% carbohydrate, 35-37% fat, and 25-27% protein on gut microbiota diversity, liver fat content and sugar metabolism. The results showed that generally diet and exercise increased gut microbiota diversity and ensured maintenance of gut microbiota associated with healthy outcomes. Liver fat content was decreased the most with diet and exercise and by nearly 50% but not all subjects responded the same with responders and non-responders identified. It was concluded that there is a necessity for personalisation of diet and exercise programmes for the treatment of NAFLD. This study could be used by healthcare professionals to understand that gut microbiota diversity may be improved by diet and exercise, however not everyone may be similarly affected. Until more is understood about the gut microbiota, it may be necessary to try different diet and exercise regimes, which are optimal for each individual.

Abstract

Exercise and diet are treatments for nonalcoholic fatty liver disease (NAFLD) and prediabetes, however, how exercise and diet interventions impact gut microbiota in patients is incompletely understood. We previously reported a 8.6-month, four-arm (Aerobic exercise, n = 29; Diet, n = 28; Aerobic exercise + Diet, n = 29; No intervention, n = 29) randomized, singe blinded (for researchers), and controlled intervention in patients with NAFLD and prediabetes to assess the effect of interventions on the primary outcomes of liver fat content and glucose metabolism. Here we report the third primary outcome of the trial-gut microbiota composition-in participants who completed the trial (22 in Aerobic exercise, 22 in Diet, 23 in Aerobic exercise + Diet, 18 in No Intervention). We show that combined aerobic exercise and diet intervention are associated with diversified and stabilized keystone taxa, while exercise and diet interventions alone increase network connectivity and robustness between taxa. No adverse effects were observed with the interventions. In addition, in exploratory ad-hoc analyses we find that not all subjects responded to the intervention in a similar manner, when using differentially altered gut microbe amplicon sequence variants abundance to classify the responders and low/non-responders. A personalized gut microbial network at baseline could predict the individual responses in liver fat to exercise intervention. Our findings suggest an avenue for developing personalized intervention strategies for treatment of NAFLD based on host-gut microbiome ecosystem interactions, however, future studies with large sample size are needed to validate these discoveries. The Trial Registration Number is ISRCTN 42622771.

Lifestyle medicine

Fundamental Clinical Imbalances : Digestive, absorptive and microbiological
Patient Centred Factors : Mediators/Insulin resistance
Environmental Inputs : Diet ; Nutrients ; Physical exercise
Personal Lifestyle Factors : Nutrition ; Exercise and movement
Functional Laboratory Testing : Blood ; Stool

Methodological quality

Jadad score : 2
Allocation concealment : No

Metadata