Plain language summary
Obesity is an important risk factor for chronic diseases. Aside from well-established mechanisms such as obesity-induced inflammation, alterations in sugar and lipid metabolism, and steroid hormone signalling, imbalances in the composition of the gut microbiome have also been linked to the progression of obesity and its cardio-metabolic sequelae. The aim of this study was to investigate whether intermittent calorie restriction (ICR) (operationalised as the 5:2 diet) or continuous calorie restriction (CCR) induced alterations in the gut microbiome, and to which extent these were associated with overall weight loss irrespective of the dietary intervention in overweight or obese adults. This study was conducted using data and samples of the HELENA trial which was a parallel-arm randomised controlled trial. Participants were randomly assigned to one of three groups, i.e., an ICR (n = 49), a CCR (n = 49), or a control group (n = 52) over a 50-week period in a 1:1:1 ratio. Results showed that the type of calorie restriction or the amount of weight lost were not accompanied by substantial and consistent shifts in gut microbiome composition or the abundance of individual bacterial taxa. Authors conclude that moderate ICR or CCR interventions as well as an overall moderate weight loss induced by calorie restriction (irrespective of which form) may not be associated with significant changes in the gut microbiome of overweight and obese adults, notwithstanding observed metabolic improvements.
Abstract
BACKGROUND The gut microbiota has been suggested to play a significant role in the development of overweight and obesity. However, the effects of calorie restriction on gut microbiota of overweight and obese adults, especially over longer durations, are largely unexplored. METHODS Here, we longitudinally analyzed the effects of intermittent calorie restriction (ICR) operationalized as the 5:2 diet versus continuous calorie restriction (CCR) on fecal microbiota of 147 overweight or obese adults in a 50-week parallel-arm randomized controlled trial, the HELENA Trial. The primary outcome of the trial was the differential effects of ICR versus CCR on gene expression in subcutaneous adipose tissue. Changes in the gut microbiome, which are the focus of this publication, were defined as exploratory endpoint of the trial. The trial comprised a 12-week intervention period, a 12-week maintenance period, and a final follow-up period of 26 weeks. RESULTS Both diets resulted in ~5% weight loss. However, except for Lactobacillales being enriched after ICR, post-intervention microbiome composition did not significantly differ between groups. Overall weight loss was associated with significant metabolic improvements, but not with changes in the gut microbiome. Nonetheless, the abundance of the Dorea genus at baseline was moderately predictive of subsequent weight loss (AUROC of 0.74 for distinguishing the highest versus lowest weight loss quartiles). Despite the lack of consistent intervention effects on microbiome composition, significant study group-independent co-variation between gut bacterial families and metabolic biomarkers, anthropometric measures, and dietary composition was detectable. Our analysis in particular revealed associations between insulin sensitivity (HOMA-IR) and Akkermansiaceae, Christensenellaceae, and Tanerellaceae. It also suggests the possibility of a beneficial modulation of the latter two intestinal taxa by a diet high in vegetables and fiber, and low in processed meat. CONCLUSIONS Overall, our results suggest that the gut microbiome remains stable and highly individual-specific under dietary calorie restriction. TRIAL REGISTRATION The trial, including the present microbiome component, was prospectively registered at ClinicalTrials.gov NCT02449148 on May 20, 2015.
Methodological quality
Jadad score
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3
Allocation concealment
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Yes
