Sex, Food, and the Gut Microbiota: Disparate Response to Caloric Restriction Diet with Fiber Supplementation in Women and Men

Mol Nutr Food Res. 2021 Apr;65(8):e2000996. doi: 10.1002/mnfr.202000996. Epub 2021 Mar 9.


Scope: Dietary-based strategies are regularly explored in controlled clinical trials to provide cost-effective therapies to tackle obesity and its comorbidities. The article presents a complementary analysis based on a multivariate multi-omics approach of a caloric restriction intervention (CRD) with fiber supplementation to unveil synergic effects on body weight control, lipid metabolism, and gut microbiota.

Methods and results: The study explores fecal bile acids (BAs) and short-chain fatty acids (SCFAs), plasma BAs, and fecal shotgun metagenomics on 80 overweight participants of a 12-week caloric restriction clinical trial (-500 kcal day-1 ) randomly allocated into fiber (10 g day-1 inulin + 10 g day-1 resistant maltodextrin) or placebo (maltodextrin) supplementation groups. The multi-omic data integration analysis uncovered the benefits of the fiber supplementation and/or the CRD (e.g., increase of Parabacteroides distasonis and fecal propionate), showing sex-specific effects on either adiposity and fasting insulin; effects thought to be linked to changes of specific gut microbiota species, functional genes, and bacterially produced metabolites like SCFAs and secondary BAs.

Conclusions: This study identifies diet-microbe-host interactions helping to design personalised interventions. It also suggests that sex perspective should be considered routinely in future studies on dietary interventions efficacy. All in all, the study uncovers that the dietary intervention is more beneficial for women than men.

Keywords: dietary fiber; gut microbiome; inulin; metabolomics; multi-omics; obesity; resistant maltodextrin; weight loss.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteroidetes
  • Bile Acids and Salts / metabolism
  • Biomarkers
  • Caloric Restriction*
  • Dietary Fiber / pharmacology*
  • Dietary Supplements
  • Fatty Acids, Volatile / blood
  • Fatty Acids, Volatile / metabolism
  • Feces / chemistry
  • Feces / microbiology
  • Female
  • Gastrointestinal Microbiome / physiology*
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Sex Factors
  • Weight Loss


  • Bile Acids and Salts
  • Biomarkers
  • Dietary Fiber
  • Fatty Acids, Volatile

Supplementary concepts

  • Parabacteroides distasonis