Effects of probiotics and postbiotics on cardiometabolic disease risk factors: a metagenomic approach to elucidate possible mechanisms of action and new obesity biomarkers

Les malalties cardiovasculars (MCVs) són la principal causa de mort al mon, juntament amb les malalties cardiometabòliques (MCM). L’objectiu principal és avaluar els efectes dels probiòtics i postbiòtics, consumits sols o amb altres compostos bioactius, en forma de càpsula/pols o afegits a matrius alimentàries, sobre els factors de risc de MCMs, particularment l’obesitat. A més, dilucidar possibles mecanismes d’acció, revelar nous biomarcadors d’obesitat i determinar possibles associacions de la microbiota intestinal amb la ingesta dietètica i paràmetres clínics. Es van realitzar cinc estudis: una revisió sistemàtica i metaanàlisi i una revisió narrativa per integrar la literatura disponible sobre la relació i l'eficàcia dels probiòtics i productes lactis fermentats (PLF) sobre els factors de risc MCM; dos estudis d’intervenció nutricional en subjectes amb obesitat abdominal que van consumir Bifidobacterium animalis subsp. lactis CECT 8145 (Ba8145) per avaluar els efectes sobre els factors de risc de MCM i la microbiota intestinal; un estudi transversal amb subjectes prims i amb sobrepès/obesitat per diferenciar la microbiota intestinal i determinar associacions amb variables clíniques i la ingesta dietètica. En conclusió, el consum regular de PLF redueix el risc de MCM i la suplementació amb probiòtics millora els factors de risc de MCM. El Ba8145 consumit com a probiòtic o postbiòtic redueix els marcadors antropomètrics d’adipositat. El postbiòtic Ba8145 va millorar paràmetres glucèmics, la pressió arterial diastòlica i pressió del pols. Els efectes beneficiosos del Ba8145 es podrien explicar parcialment per canvis en la microbiota intestinal. A més, l’anàlisi metagenòmic va mostrar possibles biomarcadors d’obesitat i noves associacions entre la microbiota intestinal amb la ingesta dietètica i els paràmetres clínics. L’addició de probiòtics o postbiòtics a les estratègies dietètiques actuals podria conduir a noves perspectives pel que fa al maneig de les MCM en humans amb almenys un factor de risc de MCM.Las enfermedades cardiovasculares (ECV) son la principal causa de muerte en el mundo, junto con las enfermedades cardiometabólicas (ECM). El objetivo principal es evaluar los efectos de los probióticos y postbióticos, consumidos solos o con otros compuestos bioactivos, en forma de cápsulas/polvo o añadidos a matrices alimenticias sobre los factores de riesgo de ECM, particularmente la obesidad. Además, dilucidar posibles mecanismos de acción, revelar nuevos biomarcadores de obesidad y determinar posibles asociaciones de la microbiota intestinal con la ingesta dietética y parámetros clínicos. Se realizaron cinco estudios: una revisión sistemática y metaanálisis y una revisión narrativa para integrar toda la literatura disponible sobre la relación y efectividad de los probióticos y productos lácteos fermentados (PLF) en los factores de riesgo de ECM; dos estudios de intervención nutricional en sujetos con obesidad abdominal que consumieron Bifidobacterium animalis subsp. lactis CECT 8145 (Ba8145) para evaluar los efectos sobre factores de riesgo de ECM y sobre la microbiota intestinal; un estudio transversal con sujetos delgados y con sobrepeso/obesidad para diferenciar la microbiota intestinal y determinar asociaciones con variables clínicas y ingesta dietética. En conclusión, el consumo regular de PLF reduce el riesgo de ECM, y la suplementación con probióticos mejora los factores de riesgo de ECM. El Ba8145 consumido como probiótico o postbiótico reduce los biomarcadores antropométricos de adiposidad. El postbiótico Ba8145 tuvo efectos beneficiosos sobre los parámetros glucémicos, presión arterial diastólica y presión del pulso. Los efectos beneficiosos del Ba8145 podrían explicarse parcialmente por cambios en la microbiota intestinal. Además, el análisis metagenómico mostró posibles biomarcadores de obesidad y nuevas asociaciones entre la microbiota intestinal con la ingesta dietética y parámetros clínicos. La adición de probióticos o postbióticos a las estrategias dietéticas actuales podría conducir a nuevas perspectivas para el manejo de las CMD en humanos con al menos un factor de riesgo de ECM.Cardiovascular diseases (CVDs) are the leading cause of death globally, along with cardiometabolic diseases (CMDs). The main objective is to evaluate the effects of probiotics and postbiotics, consumed alone or with other bioactive compounds, and consumed in capsule/powder form or added into dietary matrices, on CMD risk factors, particularly obesity. Moreover, to elucidate possible mechanisms of action, reveal new obesity biomarkers and determine possible associations of the gut microbiota with dietary intake and clinical parameters. Five studies were carried out: a systematic review and meta-analysis and a narrative review to integrated all the available literature on the relationship and effectiveness of probiotics and fermented dairy products on CMDs risk factors; two randomized controlled trials in subjects with abdominal obesity who consumed Bifidobacterium animalis subsp. lactis CECT 8145 (Ba8145) to assess the effects on CMD risk factors and on the gut microbiota; a cross-sectional study with lean and overweight/obese subjects to differentiate gut microbiota and to determine its association with clinical variables and dietary intake. Therefore, the regular consumption of fermented dairy products is associated with a reduced risk of CMDs, and probiotic supplementation improves CMD risk factors. Ba8145 consumed as a probiotic or postbiotic reduces anthropometric adiposity biomarkers. Postbiotic Ba8145 had beneficial effects on glycemic parameters, diastolic blood pressure and pulse pressure. Beneficial effects of Ba8145 could be partially explained by changes in the gut microbiota. Furthermore, the metagenomic analysis showed possible obesity biomarkers, and new associations between gut microbiota with dietary intake and clinical parameters. The addition of probiotic or postbiotic consumption to the current recommended dietary strategies could lead to new perspectives regarding the management of CMDs in humans with at least one CMD risk factor

Red-fleshed apples rich in anthocyanins and white-fleshed apples modulate the aorta and heart proteome in hypercholesterolaemic rats: the AppleCOR study

The impact of a red-fleshed apple (RFA) rich in anthocyanins (ACNs), a white-fleshed apple (WFA) without ACNs, and an extract infusion from Aronia fruit (AI) equivalent in dose of cyanidin-3-O-galactoside (main ACN) as RFA was determined by the proteome profile of aorta and heart as key cardiovascular tissues. Hypercholesterolaemic Wistar rats were separated into six groups (n = 6/group; three males and three females) and the proteomic profiles were analyzed using nanoliquid chromatography coupled to mass spectrometry. No adverse events were reported and all products were well tolerated. RFA downregulated C1QB and CFP in aorta and CRP in heart. WFA downregulated C1QB and CFP in aorta and C9 and C3 in aorta and heart, among other proteins. AI downregulated PRKACA, IQGAP1, and HSP90AB1 related to cellular signaling. Thus, both apples showed an anti-inflammatory effect through the complement system, while RFA reduced CRP. Regardless of the ACN content, an apple matrix effect was observed that involved different bioactive components, and inflammatory proteins were reduced.The work summarized in this manuscript was supported in part by grants (Grant Nos. MEFOPC Project, AGL2012-40144-C03-02, and AppleCOR Project, AGL2016-76943-C2-2-R) from the Ministerio de Economía, Industria y Competitividad, the Agencia Estatal de Investigación (AEI), and the European Regional Development Fund (ERDF). L. Rubió enjoys a Sara Borrell post-doctoral grant (CD14/00275; Spain), A. Pedret enjoys a post-doctoral grant (PTQ-15-08068; Spain), Ú. Catalán enjoys a Pla estratègic de recerca i innovació en salut (PERIS) post-doctoral grant (SLT002/16/00239; Catalunya, Spain), and S.Yuste enjoys a grant from the University of Lleida. M.J. Motilva thanks to Consejo Superior de Investigaciones Científicas-CSIC for partial funding through the “Ayudas incorporación a escalas científicas CSIC, 2018” (Reference 201870I129). We also thank the support of Institut d’Investigació Sanitària Pere Virgili (IISPV) and Fundació EURECAT, Reus, Spain. NFOC- Salut group is a consolidated research group of Generalitat de Catalunya, Spain (2014 SGR 873 and 2017 SGR 522)

Gut microbiota profile and its association with clinical variables and dietary intake in overweight/obese and lean subjects: A cross-sectional study

We aimed to differentiate gut microbiota composition of overweight/obese and lean subjects and to determine its association with clinical variables and dietary intake. A cross-sectional study was performed with 96 overweight/obese subjects and 32 lean subjects. Anthropometric parameters were positively associated with Collinsella aerofaciens, Dorea formicigenerans and Dorea longicatena, which had higher abundance the overweight/obese subjects. Moreover, different genera of Lachnospiraceae were negatively associated with body fat, LDL and total cholesterol. Saturated fatty acids (SFAs) were negatively associated with the genus Intestinimonas, a biomarker of the overweight/obese group, whereas SFAs were positively associated with Roseburia, a biomarker for the lean group. In conclusion, Dorea formicigenerans, Dorea longicatena and Collinsella aerofaciens could be considered obesity biomarkers, Lachnospiraceae is associated with lipid cardiovascular risk factors. SFAs exhibited opposite association profiles with butyrate-producing bacteria depending on the BMI. Thus, the relationship between diet and microbiota opens new tools for the management of obesity.This research was funded by the Centre for the Development of Industrial Technology (CDTI) of the Spanish Ministry of Science and Innovation, grant number CER-20191010

Effects of an Optimized Aged Garlic Extract on Cardiovascular Disease Risk Factors in Moderate Hypercholesterolemic Subjects: A Randomized, Crossover, Double-Blind, Sustainedand Controlled Study

The consumption of aged black garlic (ABG) has been related to improvements in several cardiovascular disease (CVD) risk factors. However, the extent of the beneficial effects depends on the garlic aging process and the amount and type of chemical compounds accumulated. The main objective of this study was to assess the effect of daily intake of a well-characterized ABG extract with a standardized S-allyl-L-cysteine (SAC) yield in combination with dietary recommendations regarding CVD risk factors in individuals with moderate hypercholesterolemia. Sixty-seven hypercholesterolemic individuals with low-density lipoprotein cholesterol levels ≥115 mg/dL were randomized in a crossover, double-blind, sustained, and controlled intervention study. The participants consumed 250 mg (1.25 mg SAC)/tablet/day ABG or a placebo for 6 weeks, with 3 weeks of washout. Blood and pulse pressure and other CVD risk biomarkers were determined at the beginning and end of each intervention. At 6 weeks, ABG extract reduced diastolic blood pressure (DBP) (mean (95% CI) −5.85 (−10.5; −1.3) mm Hg) compared to the placebo, particularly in men with a DBP > 75 mm Hg. The consumption of an improved ABG extract with 1.25 mg of SAC decreased DBP, particularly in men with moderate hypercholesterolemia. The potential beneficial effects of ABG may contribute to obtaining an optimal DBP