Calorie restriction improves metabolic state independently of gut microbiome composition: a randomized dietary intervention trial

Solomon A. Sowah, Alessio Milanese, Ruth Schübel, Jakob Wirbel, Ece Kartal, Theron S. Johnson, Frank Hirche, Mirja Grafetstätter, Tobias Nonnenmacher, Romy Kirsten, Marina López-Nogueroles, Agustín Lahoz, Kathrin V. Schwarz, Jürgen G. Okun, Cornelia M. Ulrich, Johanna Nattenmüller, Arnold von Eckardstein, Daniel Müller, Gabriele I. Stangl, Rudolf KaaksTilman Kühn*, Georg Zeller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)
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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.
Original languageEnglish
Article number30
JournalGenome Medicine
Volume14
Early online date14 Mar 2022
DOIs
Publication statusEarly online date - 14 Mar 2022

Keywords

  • Research
  • Obesity
  • Overweight
  • Weight loss
  • Gut microbiome
  • Intermittent calorie restriction

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