What Effect Does the Gut Microbiome Have in Cardiometabolic Health in Prediabetes?

The personalized postprandial-targeting (PPT) diet is associated with greater changes in gut microbiota composition and overall greater dietary modifications, compared with the Mediterranean-style diet (MED) in patients with prediabetes, according to a study in Gut.

Researchers reported ad hoc analysis outcomes of a 6-month dietary intervention (ClincialTrials.gov Identifier: NCT03222791), including high-resolution assessment of the dietary changes and microbiome compositional changes, in the MED and PPT diets.

Eligible participants for the randomized clinical trial had fasting plasma glucose levels between 100 and 125 mg/dL (5.6 and 6.9 mmol/L), hemoglobin A1c (HbA1c) level between 5.7% and 6.5% (39 and 48 mmol/mol), and were aged 18 to 65 years.

Phase 1 included a 6-month intervention that targeted glycemic control, and phase 2 included a 6-month follow-up. After completing the run-in period, 200 individuals were randomly assigned 1:1 to the MED or PPT diet.

The participants were asked to record their full dietary intake in real time each day using a smartphone app. Data were obtained for blood, continuous glucose monitoring (CGM) and anthropometric measurements, and stool samples were collected for microbiome analysis.

The overall dietary shift in the MED group was smaller vs the PPT group; and, the 2 groups had significant differences in most of the nutrients assessed. The PPT group had a significantly reduced carbohydrate intake from baseline (95% CI, -17.9% to -15.6% kcal), and MED group had a slightly increased carbohydrate intake (95% CI, 1.0% to 2.5% kcal). Total dietary fat intake and for the different fat subtypes was significantly increased within the PPT group.

Study authors used shotgun metagenomic sequencing data from fecal samples of the participants at baseline and at 6 months to analyze the effects of the dietary intervention on gut microbiome composition. The overall gut microbiome diversity and richness increased more in the PPT group (1-sided t-test, P =.007 and P =.00017, respectively) vs the MED arm (1-sided t-test, P =.18 and P =.04, respectively). This change in difference between the 2 diet groups was not statistically significant (MW test, P =.55 and .17, respectively).

The researchers identified 30 significant mediation effects (indirect effect; P <.05) in 9 bacterial species that partially mediate the effect of different dietary changes on clinical outcomes. Three bacterial species (from Bacteroidales, Lachnospiraceae, and Oscillospirales orders) had a significant partial mediation effect on the association of PPT adherence with clinical outcomes of HbA1c, high-density lipoprotein cholesterol, and triglycerides.

Investigators also found 5 significant correlations (P <.05, false discovery rate corrected) of 4 bacterial species (from the Lachnospiraceae, Ruminococcaceae, and Coriobacteriaceae families) with the ranked difference between measured and predicted change in the predictors of basal metabolic rate, including daily time of glucose levels above 140 mg/dL, mean CGM glucose, and low-density lipoprotein cholesterol.

Study limitations include the relatively small sample size and focusing only on microbiome compositional aspects.

“Our findings suggest concrete microbiota species targets, which may form the basis for future mechanistic experiments on their role in human diet and health, as well as potential therapeutic directions to be evaluated in preclinical and intervention studies to improve cardiometabolic health in prediabetes,” the study authors wrote.

Disclosure: The funding for the original RCT study was provided jointly by Janssen Pharmaceuticals and DayTwo Company. One of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

This article originally appeared on Gastroenterology Advisor