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      Dose-Dependent Effects of Multispecies Probiotic Supplementation on the Lipopolysaccharide (LPS) Level and Cardiometabolic Profile in Obese Postmenopausal Women: A 12-Week Randomized Clinical Trial

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          Abstract

          During the postmenopausal period, the risk of cardiovascular diseases is increased in many obese women and is associated with a worse cardiometabolic profile and a sub-chronic low-grade systemic inflammation caused by a gut barrier permeability dysfunction. Here, we tested whether administration of two different dosages of the multispecies probiotic Ecologic ® Barrier influenced the cardiometabolic biochemical parameters and lipopolysaccharide levels, the latter used as a marker of increased gut permeability in obese postmenopausal women. A total of 81 obese Caucasian postmenopausal women participated in the trial. The subjects were randomly assigned to three groups that received a placebo, a low dose (LD) (2.5 × 10 9 colony forming units (CFU) per day), or a high dose (HD) (1 × 10 10 CFU per day) of lyophilisate powder containing live multispecies probiotic bacteria. The probiotic supplement was administered each day in two equal portions for 12 weeks. We found significant ( p < 0.05) favorable changes (mostly large or medium effects) in the evaluated parameters in both the HD and LD groups but not in the placebo group. In the HD group, lipopolysaccharide, waist, fat mass, subcutaneous fat, uric acid, total cholesterol, triglycerides, low-density lipoprotein cholesterol, glucose, insulin, and insulin-resistant index (HOMA-IR) were improved. Similar changes were observed in the LD group, except for lipopolysaccharide, uric acid, triglycerides, and glucose levels. Additionally, significant differences were observed in both groups in terms of fat percentage and visceral fat. When the mean changes were compared between the three groups, statistically significant differences in lipopolysaccharide levels, uric acid, glucose, insulin, and HOMA-IR were found. Post hoc tests revealed significant differences in the mean changes (mostly medium effects) between the HD and LD groups for uric acid, glucose, insulin, and HOMA-IR. In the 12-week randomized, placebo-controlled, double-blind intervention, we observed that supplementation with the multispecies probiotic Ecologic ® Barrier favorably affected the risk factors in a dose-dependent manner, showing beneficial effects on the cardiometabolic parameters and gut permeability of the patients. Our results suggest that this product can be effective in the prevention and treatment of cardiovascular diseases in obese postmenopausal women.

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          Most cited references 23

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          Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide.

          Recent metabolomics and animal model studies show trimethylamine-N-oxide (TMAO), an intestinal microbiota-dependent metabolite formed from dietary trimethylamine-containing nutrients such as phosphatidylcholine (PC), choline, and carnitine, is linked to coronary artery disease pathogenesis. Our aim was to examine the prognostic value of systemic choline and betaine levels in stable cardiac patients. We examined the relationship between fasting plasma choline and betaine levels and risk of major adverse cardiac events (MACE = death, myocardial infraction, stroke) in relation to TMAO over 3 years of follow-up in 3903 sequential stable subjects undergoing elective diagnostic coronary angiography. In our study cohort, median (IQR) TMAO, choline, and betaine levels were 3.7 (2.4-6.2)μM, 9.8 (7.9-12.2)μM, and 41.1 (32.5-52.1)μM, respectively. Modest but statistically significant correlations were noted between TMAO and choline (r = 0.33, P < 0.001) and less between TMAO and betaine (r = 0.09, P < 0.001). Higher plasma choline and betaine levels were associated with a 1.9-fold and 1.4-fold increased risk of MACE, respectively (Quartiles 4 vs. 1; P < 0.01, each). Following adjustments for traditional cardiovascular risk factors and high-sensitivity C-reactive protein, elevated choline [1.34 (1.03-1.74), P < 0.05], and betaine levels [1.33 (1.03-1.73), P < 0.05] each predicted increased MACE risk. Neither choline nor betaine predicted MACE risk when TMAO was added to the adjustment model, and choline and betaine predicted future risk for MACE only when TMAO was elevated. Elevated plasma levels of choline and betaine are each associated with incident MACE risk independent of traditional risk factors. However, high choline and betaine levels are only associated with higher risk of future MACE with concomitant increase in TMAO.
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            Antidiabetic effect of probiotic dahi containing Lactobacillus acidophilus and Lactobacillus casei in high fructose fed rats.

            We investigated the effect of low-fat (2.5%) dahi containing probiotic Lactobacillus acidophilus and Lactobacillus casei on progression of high fructose-induced type 2 diabetes in rats. Diabetes was induced in male albino Wistar rats by feeding 21% fructose in water. The body weight, food and water intakes, fasting blood glucose, glycosylated hemoglobin, oral glucose tolerance test, plasma insulin, liver glycogen content, and blood lipid profile were recorded. The oxidative status in terms of thiobarbituric acid-reactive substances and reduced glutathione contents in liver and pancreatic tissues were also measured. Values for blood glucose, glycosylated hemoglobin, glucose intolerance, plasma insulin, liver glycogen, plasma total cholesterol, triacylglycerol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and blood free fatty acids were increased significantly after 8 wk of high fructose feeding; however, the dahi-supplemented diet restricted the elevation of these parameters in comparison with the high fructose-fed control group. In contrast, high-density lipoprotein cholesterol decreased slightly and was retained in the dahi-fed group. The dahi-fed group also exhibited lower values of thiobarbituric acid-reactive substances and higher values of reduced glutathione in liver and pancreatic tissues compared with the high fructose-fed control group. The probiotic dahi-supplemented diet significantly delayed the onset of glucose intolerance, hyperglycemia, hyperinsulinemia, dyslipidemia, and oxidative stress in high fructose-induced diabetic rats, indicating a lower risk of diabetes and its complications.
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              Postmenopausal status and early menopause as independent risk factors for cardiovascular disease: a meta-analysis.

              Loss of ovarian function and subsequent deficiency of endogenous estrogens is suggested to enhance cardiovascular disease risk and related death after menopause. The aim was to obtain valid estimates of the cardiovascular disease risk associated with postmenopausal status and early menopause. A literature search of observational studies was performed using PubMed and EMBASE (1966 to May 1, 2004). Eighteen studies on postmenopausal status and age at menopause in relation to cardiovascular disease were selected. Six studies investigated menopausal status, nine studies investigated menopausal age, and three studied both. General variance-based methods were used to pool relative risk estimates and corresponding 95% confidence intervals. Stratification was performed for study design, type of menopause, outcome, and adjustment for age and smoking. The pooled relative risk estimate for postmenopausal versus premenopausal status and cardiovascular disease was 1.36 (95% CI, 1.15-1.60). In the stratified analysis, the pooled effect was 0.96 (95% CI, 0.77-1.21) after controlling for age and smoking. The pooled effect of bilateral oophorectomy on cardiovascular disease was 2.62 (95% CI, 2.05-3.35). For early menopause and cardiovascular disease, with the menopausal age category containing 50 years as a reference, the pooled relative risk estimate was 1.25 (95% CI, 1.15-1.35). In the stratified analysis, the pooled effect was 1.38 (95% CI, 1.21-1.58) after controlling for age and smoking. The pooled effect of bilateral oophorectomy on cardiovascular disease was 4.55 (95% CI, 2.56-8.01). Overall, there was no convincing relationship between postmenopausal status and cardiovascular disease. However, there was a modest effect of early menopause on cardiovascular disease. The effect was more pronounced for women with an artificial menopause than for women with a natural menopause.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                15 June 2018
                June 2018
                : 10
                : 6
                Affiliations
                [1 ]Department of Education and Treatment of Obesity and Metabolic Disorders, University of Medical Sciences in Poznań, Szamarzewskiego Str. 84, 60-569 Poznań, Poland; mszulinska1@ 123456wp.pl (M.S.); pawelbogdanski73@ 123456gmail.com (P.B.)
                [2 ]Department of Biochemistry and Human Nutrition, Pomeranian Medical University in Szczecin, Broniewskiego Str. 24, 71-460 Szczecin, Poland
                [3 ]Winclove Probiotics, Hulstweg 11, 1032 LB Amsterdam, The Netherlands; s.vanhemert@ 123456winclove.nl
                [4 ]Department of Rheumatology and Rehabilitation, University of Medical Sciences in Poznań, 28 Czerwca 1956r Str. 135/147, 61-55 Poznań, Poland; msobieska@ 123456ump.edu.pl
                Author notes
                [* ]Correspondence: sanprobi@ 123456sanprobi.pl ; Tel.: +48-501-653-277
                Article
                nutrients-10-00773
                10.3390/nu10060773
                6024794
                29914095
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                Categories
                Article

                Nutrition & Dietetics

                probiotics, obesity, metabolic profile, postmenopausal women

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