Changes in Gut Microbiota-Related Metabolites and Long-term Successful Weight Loss in Response to Weight-Loss Diets: The POUNDS Lost Trial.

Yoriko Heianza, Dianjianyi Sun, Steven R Smith, George A Bray, Frank M Sacks, Lu Qi

Journal: Diabetes care 2018;41(3):413-419

PMID: 29305401

Plain Language Summary

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Evidence has demonstrated that weight loss contributes to lowering the risk of developing type 2 diabetes among obese patients. The aim of this study was to examine whether diet-induced metabolites were associated with improvements in adiposity and metabolism during a weight-loss diet intervention in 510 overweight and obese individuals. Participants were randomly assigned to one of four diets with varying macronutrient composition to adhere to for six months. Blood samples and anthropometric data were taken at baseline and 6 months to monitor changes. This study found that overweight and obese individuals with reduced choline or L-carnitine levels achieved greater improvements of adiposity and energy metabolism. Based on these results, the authors conclude that metabolites are predictive of patient responsiveness to dietary interventions, and suggest further studies evaluate these effects in the pre-diabetic obese population.

Abstract

OBJECTIVE

Adiposity and the gut microbiota are both related to the risk of type 2 diabetes. We aimed to comprehensively examine how changes induced by a weight-loss diet intervention in gut microbiota-related metabolites, such as trimethylamine -oxide (TMAO) and its precursors (choline and l-carnitine), were associated with improvements in adiposity and regional fat deposition.

RESEARCH DESIGN AND METHODS

This study included 510 overweight and obese individuals who were randomly assigned one of four diets varying in macronutrient intake. We examined associations of 6-month changes in blood metabolites (TMAO, choline, and l-carnitine) with improvements in body weight (BW), waist circumference (WC), body fat composition, fat distribution, and resting energy expenditure (REE).

RESULTS

Individuals with a greater reduction of choline ( < 0.0001) and l-carnitine ( < 0.01) rather than TMAO showed significant losses of BW and WC at 6 months. The reduction of choline was significantly predictive of decreases in body fat composition, fat distribution, and REE. Results of sensitivity analysis showed that the baseline diabetes risk status, such as the presence of hyperglycemia (31% of the total participants) and fasting glucose levels, did not modify the associations. Early changes in choline and l-carnitine were significantly predictive of weight loss over 2 years ( < 0.05 for all). Individuals with increases in choline or l-carnitine were 2.35-times (95% CI 1.38, 4.00) or 1.77-times (1.06, 2.95) more likely to fail to lose weight (-5% or more loss) at 2 years.

CONCLUSIONS

Overweight and obese individuals who showed decreases in circulating choline or l-carnitine levels achieved greater improvements of adiposity and energy metabolism by eating a low-calorie weight-loss diet, suggesting that such metabolites are predictive of individuals' response to the treatment. Further investigations are necessary to confirm our findings, particularly in a population with prediabetes that is more representative of the U.S. population with obesity.

© 2018 by the American Diabetes Association.

Address: Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA.; Translational Research Institute, Florida Hospital, Orlando, FL.; Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA.; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.; Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA [email protected].; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.

Patient Centred Factor

Laboratory Testing

Modifiable Lifestyle Factors

Jadad Score

Allocation Concealment

Bioactive Substances

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