Gut microbiota dynamics and association with chronic kidney disease: A longitudinal study within the PREDIMED-Plus trial.

AIMS: Chronic kidney disease (CKD) represents a global health concern, disproportionately affecting the elderly with heightened cardiovascular risk. The emerging focus on the gut microbiota's role in CKD pathophysiology represents a pivotal area in nephrology; however, the evidence on this topic is limited. This observational prospective study, in the framework of the PREDIMED-Plus trial, investigates associations between gut microbiota composition and the 1-year trajectory of CKD in 343 participants aged 55-75 years with high cardiovascular risk. MATERIALS AND METHODS: Kidney function was assessed at baseline and at 1-year of follow-up through the estimated glomerular filtration rate based on cystatin C (eGFR-CysC) and CKD defined by eGFR-CysC <60 mL/min/1.73 m2. Participants were grouped based on their 1-year CKD trajectory: Group 1 maintained normal status or improved from CKD to normal, while Group 2 maintained CKD or worsened from normal to CKD. Fecal microbiota composition was assessed through 16S sequencing. KEY FINDINGS: We observed differences in gut microbiota composition between CKD trajectory groups. Notably, the baseline relative abundance of Lachnoclostridium and Lachnospira, both butyrate-producing genera, was lower in participants maintaining or progressing to CKD. Longitudinally, a decrease in Lachnospira abundance was associated with CKD progression. The improved Chao1 index after 1-year follow-up suggests a link between enhanced microbial richness and stable/better kidney function. SIGNIFICANCE: The findings underscore the potential of gut microbiota analysis in non-invasively monitoring CKD, especially in older populations, and hint at future interventions targeting gut microbiota to manage CKD progression. Further research is needed for causal relationships and generalizability.

Effect of 1-year lifestyle intervention with energy-reduced Mediterranean diet and physical activity promotion on the gut metabolome and microbiota: a randomized clinical trial.

BACKGROUND: The health benefits of the Mediterranean diet (MedDiet) have been linked to the presence of beneficial gut microbes and related metabolites. However, its impact on the fecal metabolome remains poorly understood. OBJECTIVES: Our goal was to investigate the weight-loss effects of a 1-y lifestyle intervention based on an energy-reduced MedDiet coupled with physical activity (intervention group), compared with an ad libitum MedDiet (control group), on fecal metabolites, fecal microbiota, and their potential association with cardiovascular disease risk factors. METHODS: A total of 400 participants (200 from each study group), aged 55-75 y, and at high cardiovascular disease risk, were included. Dietary and lifestyle information, anthropometric measurements, blood biochemical parameters, and stool samples were collected at baseline and after 1 y of follow-up. Liquid chromatography-tandem mass spectrometry was used to profile endogenous fecal metabolites, and 16S amplicon sequencing was employed to profile the fecal microbiota. RESULTS: Compared with the control group, the intervention group exhibited greater weight loss and improvement in various cardiovascular disease risk factors. We identified intervention effects on 4 stool metabolites and subnetworks primarily composed of bile acids, ceramides, and sphingosines, fatty acids, carnitines, nucleotides, and metabolites of purine and the Krebs cycle. Some of these were associated with changes in several cardiovascular disease risk factors. In addition, we observed a reduction in the abundance of the genera Eubacterium hallii group and Dorea, and an increase in alpha diversity in the intervention group after 1 y of follow-up. Changes in the intervention-related microbiota profiles were also associated with alterations in different fecal metabolite subnetworks and some cardiovascular disease risk factors. CONCLUSIONS: An intervention based on an energy-reduced MedDiet and physical activity promotion, compared with an ad libitum MedDiet, was associated with improvements in cardiometabolic risk factors, potentially through modulation of the fecal microbiota and metabolome. This trial was registered at https://www.isrctn.com/ as ISRCTN89898870 (https://doi.org/10.1186/ISRCTN89898870).

Plasma metabolite profile of legume consumption and future risk of type 2 diabetes and cardiovascular disease.

BACKGROUND: Legume consumption has been linked to a reduced risk of type 2 diabetes (T2D) and cardiovascular disease (CVD), while the potential association between plasma metabolites associated with legume consumption and the risk of cardiometabolic diseases has never been explored. Therefore, we aimed to identify a metabolite signature of legume consumption, and subsequently investigate its potential association with the incidence of T2D and CVD. METHODS: The current cross-sectional and longitudinal analysis was conducted in 1833 PREDIMED study participants (mean age 67 years, 57.6% women) with available baseline metabolomic data. A subset of these participants with 1-year follow-up metabolomics data (n = 1522) was used for internal validation. Plasma metabolites were assessed through liquid chromatography-tandem mass spectrometry. Cross-sectional associations between 382 different known metabolites and legume consumption were performed using elastic net regression. Associations between the identified metabolite profile and incident T2D and CVD were estimated using multivariable Cox regression models. RESULTS: Specific metabolic signatures of legume consumption were identified, these included amino acids, cortisol, and various classes of lipid metabolites including diacylglycerols, triacylglycerols, plasmalogens, sphingomyelins and other metabolites. Among these identified metabolites, 22 were negatively and 18 were positively associated with legume consumption. After adjustment for recognized risk factors and legume consumption, the identified legume metabolite profile was inversely associated with T2D incidence (hazard ratio (HR) per 1 SD: 0.75, 95% CI 0.61-0.94; p = 0.017), but not with CVD incidence risk (1.01, 95% CI 0.86-1.19; p = 0.817) over the follow-up period. CONCLUSIONS: This study identified a set of 40 metabolites associated with legume consumption and with a reduced risk of T2D development in a Mediterranean population at high risk of cardiovascular disease. TRIAL REGISTRATION: ISRCTN35739639.