In a recent study published in The American Journal of Clinical Nutrition, researchers investigate the health advantages of the Mediterranean weight loss program (MedDiet) and physical activity interventions on chubby and obese participants by measuring changes in fecal metabolomic- and gut microbiota.

Study: Effect of 1-year lifestyle intervention with energy-reduced Mediterranean weight loss program and physical activity promotion on the gut metabolome and microbiota: A randomized clinical trial. Image Credit: Valentyn Volkov / Shutterstock.com

Health advantages of the MedDiet

Characterised by a high intake of healthy vegetables, legumes, fruits, whole cereals, and nuts, moderate intake of seafood, low intake of dairy products and processed meats, in addition to olive oil comprising the first fat source, the standard MedDiet has been growing in global popularity.

Previous studies have investigated the health advantages of the MedDiet, which include significant heart problems (CVD), obesity, neurological, and all-cause mortality risk reductions as in comparison with suboptimal dietary patterns just like the Western weight loss program.

The high concentrations of dietary fiber and anti inflammatory nutraceuticals within the MedDiet have also been related to promoting and persisting useful gut microbiota. So far, the metabolomic consequences of those associations remain unknown.

Exploring the blood metabolome provides vital insights into how gut microbiota-derived metabolites correlate with cardiometabolic diseases. Through the usage of plasma metabolomics and 16S sequencing, researchers can elucidate how weight loss program, circulating metabolites, and gut microbiota impact cardiovascular health.

Understanding the influence of dietary interventions on each gut microbial composition and metabolomic profiles can support clinical recommendations to follow the MedDiet and other healthy diets, particularly in high-risk patients. Moreover, these data can provide foundational insights for future studies investigating the indirect effects of weight loss program on other non-cardiovascular somatic systems.

Concerning the study

In the current study, researchers used data from the PREvención con DIeta MEDiterránea (PREDIMED)-Plus randomized trial to analyze the consequences of 1 12 months of intensive lifestyle intervention on fecal metabolites, gut microbiota, and cardiovascular risk aspects, particularly in chubby and obese patients. The study comprised 400 individuals between the ages of 55 and 75 years from Alicante, Barcelona, Reus, and Valencia who were randomly divided between the intervention group (IG) and control group (CG).

Data collection included dietary and lifestyle information obtained through the er-MedDiet questionnaire, a 17-item derivation of the 14-item Mediterranean Weight loss program Adherence Screener (MEDAS) questionnaire. Blood and stool samples were also collected during baseline assessments and routine follow-up. Anthropometric measurements and demographic data were further obtained from medical and government records.

The researchers encouraged all study participants to extend their usual physical activity levels to incorporate no less than 45 minutes each day of brisk walking or an equivalent activity. All study participants were also encouraged to perform specific exercises that increase their balance, strength, and adaptability to ultimately complete 150 minutes or more of moderate-to-vigorous physical activity each week.

Changes in physical activity levels were quantified using questionnaires that assigned the metabolic equivalent of tasks (MET) min/week metrics to physical activity status and MET h/day for sedentary behaviors. The study intervention included lifestyle recommendations for physical activity and weight loss program and in-person behavioral support from a licensed dietitian for the IG group. In contrast, CG was treated ad libitum with a daily MedDiet, which was the one intervention.

Outcomes of interest were measured using liquid chromatography-tandem mass spectrometry (LC-MS) for metabolomics identification, characterization, and quantification and 16S amplicon sequencing for gut microbiome evaluations. Linear regression models and weighted gene co-expression network evaluation (WGCNA) were used to discover between-group differences and metabolomic sub-networks, respectively.

Study findings

The current study highlights the combined health advantages of a dietitian-guided MedDiet alongside physical activity in comparison with an ad libitum MedDiet.

Obese and obese participants within the IG cohort exhibited a mean weight reduction of 4.2 kg and 4.4 cm lower waist circumference than their CG counterparts. The body mass index (BMI) and total energy intake estimates of the IG group were 1.5 kg/m² and 113.9 kcal lower than controls, thus explaining the 0.1% observed reductions in glycated hemoglobin values as in comparison with controls.

Fecal metabolomic evaluation revealed a complete of 532 fecal metabolites, 4 of which were significantly different between IG and CG following one 12 months. These 4 metabolites included 4,7,10,13,16-docosapentaenoic acid (DPA) and adrenic acid, each of which decreased following the intervention, in addition to oleic acid and 3-methyl-adipic acid (3-MAA), each of which increased following intervention. While preliminary analyses suggested a further 56 metabolites of interest, these were non-significant following false discovery rate (FDR) corrections.

Network analyses grouped the 532 identified metabolites into 16 subnetworks ranging in size from Grey60 to brown. The Black, Midnight Blue, Pink, and Salmon subnetworks significantly differed between IG and CG cohorts following one 12 months of the study.

The Black subnetwork comprised ceramides and spingosines, whereas the Midnight blue subnetwork consists of purines. The Pink subnetwork metabolites included fatty acids and carnitines, whereas the Salmon network comprised bile acids.

In comparison with the CG, the IG exhibited reduced levels of the Black, Midnight Blue, and Pink subnetworks. Comparatively, the IG exhibited increased levels of the Salmon subnetwork in comparison with the CG.  

Gut microbial evaluation determined that IG Shannon and Chao1 alpha diversity indices were significantly higher than CG indices by the top of the study, with the highest two axes of the principal coordinate evaluation (PCoA) explaining 36% of the observed differences. 

The Eubacterium hallii group exhibited a big reduction in population size within the IG in comparison with the CG. A reduced abundance of Dorea was also observed but to a lesser extent than within the Eubacterium hallii group.

Conclusions

The current lifestyle intervention-based clinical trial highlights the advantages of stringent dietary supervision and physical activity engagement for at-risk chubby and obese individuals, even in comparison to equal-risk subjects consuming a similarly healthy weight loss program. The energy-reduced MedDiet and physical activity intervention within the IG, in comparison with an ad libitum MedDiet for the CG, significantly reduced weight metrics, including waist circumference and BMI.

Even with similar healthy dietary patterns, the high intensity of the dietary intervention and weight-loss intervention components, corresponding to caloric restriction and physical activity, could have significant advantages on CVD risk aspects, potentially through modulation of the fecal microbiota and metabolome. Public health policies and interventions will be tailored to individual microbiome profiles, allowing for more precise and effective strategies for stopping and managing cardiometabolic diseases.”