Hypertension is an independent and preventable risk factor for the development of cardiovascular diseases, however, little is known about the impact of gut microbiota composition in its development. We carried out comprehensive gut microbiota analysis and targeted metabolomics in a cross-sectional study of 29 non-treated hypertensive (HT) and 32 normotensive (NT) subjects. We determined fecal microbiota composition by 16S rRNA gene sequencing and bacterial functions by metagenomic analysis. The microbial metabolites analysed were short chain fatty acids (SCFA) both in plasma and feces, and trimethylamine N-oxide (TMAO) in plasma. The overall bacterial composition and diversity of bacterial community in the two groups were not significantly different. However, Ruminococcaceae NK4A214, Ruminococcaceae_UCG-010, Christensenellaceae_R-7, Faecalibacterium prausnitzii and Roseburia hominis were found to be significantly enriched in NT group, whereas, Bacteroides coprocola, Bacteroides plebeius and genera of Lachnospiraceae were increased in HT patients. We found a positive correlation between the HT-associated species and systolic and diastolic blood pressure after adjusted for measured confounders. SCFA showed antagonistic results in plasma and feces, detecting in HT subjects significant higher levels in feces and lower levels in plasma, which could indicate a less efficient SCFA absorption. Overall, our results present a disease classifier based on microbiota and bacterial metabolites to discriminate HT individuals from NT controls in a first disease grade prior to drug treatment.Hypertension is one of the leading risk factors for the development of cardiovascular diseases (CVD) globally, and lifestyle measures are effective as a preventive strategies 1 . In 2015, hypertension based on office blood pressure (BP) reported the highest rates with a global prevalence of 1.13 billion cases, and 150 million in central and eastern Europe regardless of the income countries status 2-4 .The identification of the determinants of hypertension is still challenging although it is well recognized its multifactorial etiology 5 . It has been elucidated the interplay of genetic and environmental factors related with risk-conferring behaviors, such as, smoking, lack of physical activity, alcohol consumption and unhealthy diet 6,7 .Recently, it has been evidenced the role of gut microbiota dysbiosis on the modulation of high BP, both in animal and human hypertension 8 . Mell et al. (2015) were the first to demonstrate the differential fecal microbial composition of Dahl salt-sensitive and Dahl salt-resistant rats 9 . In the same period, Yang et al. (2015) also found a clear gut dysbiosis in spontaneously hypertensive rats (SHR) mediated by a decrease in microbial richness and open Scientific RepoRtS | (2020) 10:6436 | https://doi.org/10.1038/s41598-020-63475-w www.nature.com/scientificreports www.nature.com/scientificreports/ Scientific RepoRtS | (2020) 10:6436 | https://doi.org/10.1038/s41598-020-63475-w www.nature.com/scientificreports...

BackgroundThe effects of probiotic Bifidobacterium animalis subsp. lactis CECT 8145 (Ba8145) and those of its heat-killed form (h-k Ba8145) on human anthropometric adiposity biomarkers are unknown.ObjectiveTo assess the effect of Ba8145 and h-k Ba8145 ingestion on anthropometric adiposity biomarkers.DesignRandomized, parallel, double-blind, placebo-controlled trial with abdominally obese individuals. Participants (n = 135) consumed 1 capsule/day containing 1010 colony forming unit (CFU) of Ba8145, 1010 CFU of h-k Ba8145, or placebo (maltodextrin) for 3 months.ResultsBa8145 ingestion decreased waist circumference, waist circumference/height ratio, and Conicity index (P < 0.05) versus its baseline. Changes versus the placebo group reached significance (P < 0.05) after the h-k Ba8145 treatment. Ba8145 decreased the body mass index compared with baseline and placebo group (P < 0.05). The decrease in visceral fat area after Ba8145 treatments reached significance (P < 0.05) only after h-k Ba8145. When analyses by gender were performed, significance remained only for women. Diastolic blood pressure and HOMA index decreased (P < 0.05) after h-k Ba8145. Gut microbiome analyses showed an increase in Akkermansia spp. after Ba8145 treatment, particularly in the live form, which was inversely related to weight (P = 0.003).ConclusionsIn abdominally obese individuals, consumption of Ba8145, both as viable and mainly as heat-killed cells, improves anthropometric adiposity biomarkers, particularly in women. An increase in the gut Akkermansia genus appears as a possible mechanism involved. Our results support Ba8145 probiotic as a complementary strategy in obesity management.

Fermented dairy foods (FDFs) and probiotics are promising tools for the prevention and management of cardiometabolic diseases (CMDs), respectively. The relation between the regular consumption of FDFs and CMD risk factors was assessed by prospective cohort studies (PCSs), and the effect of probiotic supplementation added into a dairy matrix on CMD parameters was evaluated by randomized controlled trials (RCTs). Moreover, the effects of probiotic supplementation added into a dairy matrix were compared with those administered in capsule/powder form. Twenty PCSs and 52 RCTs met the inclusion criteria for the systematic review and meta-analysis. In PCSs, fermented milk was associated with a 4% reduction in risk of stroke, ischemic heart disease, and cardiovascular mortality [RR (95% CI); 0.96 (0.94, 0.98)]; yogurt intake was associated with a risk reduction of 27% [RR (95% CI); 0.73 (0.70, 0.76)] for type 2 diabetes (T2D) and 20% [RR (95% CI); 0.80 (0.74, 0.87)] for metabolic syndrome development. In RCTs, probiotic supplementation added into dairy matrices produced a greater reduction in lipid biomarkers than when added into capsules/powder in hypercholesterolemic subjects, and probiotic supplementation by capsules/powder produced a greater reduction in T2D biomarkers than when added into dairy matrices in diabetic subjects. Both treatments (dairy matrix and capsules/powder) resulted in a significant reduction in anthropometric parameters in obese subjects. In summary, fermented milk consumption is associated with reduced cardiovascular risk, while yogurt intake is associated with a reduced risk of T2D and metabolic syndrome development in the general population. Furthermore, probiotic supplementation added into dairy matrices could be considered beneficial for lowering lipid concentrations and reducing anthropometric parameters. Additionally, probiotic capsule/powder supplementation could contribute to T2D management and reduce anthropometric parameters. However, these results should be interpreted with caution due to the heterogeneity of the studies and the different probiotic strains used in the studies. This trial is registered with PROSPERO (CRD42018091791) and the protocol can be accessed at http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42018091791.