Genetically determined gut microbial abundance and 2-year changes in central adiposity and body composition: The POUNDS lost trial

Clin Nutr. 2022 Dec;41(12):2817-2824. doi: 10.1016/j.clnu.2022.11.002. Epub 2022 Nov 5.


Background and aim: Growing evidence has linked gut microbiota with regulation of adiposity. We aimed to examine whether the genetically determined relative abundance of gut microbial taxa was associated with long-term changes in adiposity and body composition among individuals who were overweight or obese in weight-loss diet interventions.

Methods: The study included 692 participants with overweight or obese from the POUNDS Lost trial. We created a genetic risk score (GRS) for the relevant abundance of gut microbial taxa using 20 single nucleotide polymorphisms identified from a recent genome-wide association study. Body composition was assessed using dual-energy X-ray absorptiometry.

Results: Higher GRS for the relative abundance of gut microbial taxa was significantly associated with greater reductions in waist circumference, total fat mass (FM), whole-body total percentage of fat mass (FM%), and percentage of trunk fat (TF%) at 2 years (p = 0.022, 0.034, 0.023, 0.023, respectively). In addition, dietary protein significantly modified the association between GRS for gut microbial abundance and changes in total FM, FM%, and TF% (p-interactions = 0.04, 0.013, and 0.006, respectively) at 6-month, when the maximum weight loss was achieved, even though such interactions were attenuated at 2 years. In the average-protein diet group, a higher microbial abundance GRS was associated with greater reductions in total FM (p = 0.007), FM% (p = 0.002), and TF% (p < 0.001) at 6 months, while no associations were found in the high-protein diet group (p > 0.05).

Conclusion: Our results suggest that the higher genetically determined relative abundance of gut microbial taxa may be related to long-term improvement of whole-body and central fatness and body composition in response to low-calorie diet interventions.

Keywords: Body composition; Central adiposity; Diet intervention; Gut microbiome.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity / genetics
  • Body Composition
  • CD36 Antigens
  • Gastrointestinal Microbiome* / genetics
  • Genome-Wide Association Study
  • Humans
  • Obesity / genetics
  • Obesity, Abdominal
  • Overweight* / genetics


  • CD36 Antigens