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

Monika Szulińska, Igor Łoniewski, Saskia van Hemert, Magdalena Sobieska, Paweł Bogdański, Monika Szulińska, Igor Łoniewski, Saskia van Hemert, Magdalena Sobieska, Paweł Bogdański

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&reg; 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 &times; 10⁸ colony forming units (CFU) per day), or a high dose (HD) (1 &times; 1010 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&reg; 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.

Keywords: metabolic profile; obesity; postmenopausal women; probiotics.

Conflict of interest statement

I.Ł. is a foundation shareholder in Sanprobi, a probiotics distributor. However, the content of this study was not constrained by this fact. Moreover, our adherence to Nutrients’ policies on the sharing of data and materials was unaffected. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
A flowchart of the study design.

References

    1. World Health Organization Obesity, and Overweight. [(accessed on 26 January 2016)]; Available online:
    1. Rahman T., Hosen I., Islam M.M.T., Shekhar H.U. Oxidative stress, and human health. Adv. Biosci. Biotechnol. 2012;3:997–1019. doi: 10.4236/abb.2012.327123.
    1. ABriones M., Touyz R.M. Oxidative stress, and hypertension: Current concepts. Curr. Hypertens. Rep. 2010;12:135–142. doi: 10.1007/s11906-010-0100-z.
    1. GBD 2013 Mortality and Causes of Death Collaborators Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: A systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;385:117–171.
    1. Atsma F., Bartelink M.L., Grobbee D.E., van der Schouw Y.T. Postmenopausal status and early menopause as independent risk factors for cardiovascular disease: A meta-analysis. Menopause. 2006;13:265–279. doi: 10.1097/01.gme.0000218683.97338.ea.
    1. Mozaffarian D., Benjamin E.J., Go A.S., Arnett D.K., Blaha M.J., Cushman M., Das S.R., de Ferranti S., Despres J.P., Fullerton H.J., et al. Heart disease and stroke statistics—2016 update: A report from the American Heart Association. Circulation. 2016;133:e38–e360. doi: 10.1161/CIR.0000000000000350.
    1. Collins P., Webb C.M., de Villiers T.J., Stevenson J.C., Panay N., Baber R.J. Cardiovascular risk assessment in women—An update. Climacteric. 2016;19:329–336. doi: 10.1080/13697137.2016.1198574.
    1. He M., Shi B. Gut microbiota as a potential target of metabolic syndrome: The role of probiotics and prebiotics. Cell Biosci. 2017;7:54. doi: 10.1186/s13578-017-0183-1.
    1. Brown J.M., Hazen S.L. The Gut Microbial Endocrine Organ: Bacterially-Derived Signals Driving Cardiometabolic Disease. Annu. Rev. Med. 2015;66:343–359. doi: 10.1146/annurev-med-060513-093205.
    1. Ebel B., Lemetis G., Beney L., Cachon R., Sokol H., Langella P., Gervais P. Impact of probiotics on risk factors for cardiovascular diseases. A review. Crit. Rev. Food Sci. Nutr. 2014;54:175–189. doi: 10.1080/10408398.2011.579361.
    1. Yoo J.Y., Kim S.S. Probiotics, and Prebiotics: Present Status and Future Perspectives on Metabolic Disorders. Nutrients. 2016;8:173. doi: 10.3390/nu8030173.
    1. Whitman W.B., Coleman D.C., Wiebe W.J. Prokaryotes: The unseen majority. Proc. Natl. Acad. Sci. USA. 1998;95:6578–6583. doi: 10.1073/pnas.95.12.6578.
    1. The Human Microbiome Project Consortium Structure, function, and diversity of the healthy human microbiome. Nature. 2012;486:207–214.
    1. Wang Z., Klipfell E., Bennett B.J., Koeth R., Levison B.S., DuGar B., Feldstein A.E., Britt E.B., Fu X., Chung Y.M., et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011;472:57–63. doi: 10.1038/nature09922.
    1. Koeth R.A., Wang Z., Levinson B.S., Buffa J.A., Org E., Sheehy B.T., Britt E.B., Fu X., Wu Y., Li L., et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat. Med. 2013;19:576–585. doi: 10.1038/nm.3145.
    1. Tang W.H., Wang Z., Levison B.S., Levison B.S., Koeth R.A., Britt E.B., Fu X., Wu Y., Hazen S.L. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N. Engl. J. Med. 2013;368:1575–1578. doi: 10.1056/NEJMoa1109400.
    1. Wang Z., Tang W.H., Buffa J.A., Fu X., Britt E.B., Koeth R.A., Levison B.S., Fan Y., Wu Y., Hazen S.L. Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide. Eur. Heart J. 2014;35:904–910. doi: 10.1093/eurheartj/ehu002.
    1. Bennett B.J., de Aguiar Vallim T.Q., Wang Z., Shih D.M., Meng Y., Gregory J., Allayee H., Lee R., Graham M., Crooke R., et al. Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. Cell Metab. 2013;17:49–60. doi: 10.1016/j.cmet.2012.12.011.
    1. Creely S.J., McTernan P.G., Kusminski C.M., Fisher M., Da Silva N.F., Khanolkar M., Evans M., Harte A.L., Kumar S. Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes. Am. J. Physiol. Endocrinol. Metab. 2007;292:E740–E747. doi: 10.1152/ajpendo.00302.2006.
    1. Claesson M.J., Jeffery I.B., Conde S., Power S.E., O’Connor E.M., Cusack S., Harris H.M.B., Coakley M., Lakshminarayanan B., O’Sullivan O., et al. Gut microbiota composition correlates with diet and health in the elderly. Nature. 2012;488:178–184. doi: 10.1038/nature11319.
    1. Yatsunenko T., Rey F.E., Manary M.J., Trehan I., Dominguez-Bello M.G., Contreras M., Magris M., Hidalgo G., Baldassano R.N., Anokhin A.P., et al. Human gut microbiome viewed across age and geography. Nature. 2012;486:222–227. doi: 10.1038/nature11053.
    1. Muegge B.D., Kuczynski J., Knights D., Clemente J.C., González A., Fontana L., Henrissat B., Knight R., Gordon J.I. Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans. Science. 2011;332:970–974. doi: 10.1126/science.1198719.
    1. Ohland C.L., Macnaughton W.K. Probiotic Bacteria and Intestinal Epithelial Barrier Function. Am. J. Physiol. Gastrointest. Liver Physiol. 2010;298:G807–G819. doi: 10.1152/ajpgi.00243.2009.
    1. Miyauchi E., Hurley G., Melgar S., Tanabe S., Shanahan F., Nally K., O’Toole P.W. Mechanism of Protection of Transepithelial Barrier Function by Lactobacillus Salivarius: Strain-Dependence and Attenuation by Bacteriocin Production. Am. J. Physiol. Gastrointest. Liver Physiol. 2012;303:G1029–G1104. doi: 10.1152/ajpgi.00003.2012.
    1. Van Hemert S., Verwer J., Schütz B. Clinical Studies Evaluation Effects of Probiotics on Parameters of Intestinal Barrier Function. Adv. Microbiol. 2013;3:212–221. doi: 10.4236/aim.2013.32032.
    1. Van Hemert S., Ormel G. Influence of the Multispecies Probiotic Ecologic® BARRIER on Parameters of Intestinal Barrier Function. Food Nutr. Sci. 2014;5:1739–1745.
    1. Sabico S., Al-Mashharawi A., Al-Daghri N., Yakout S., Alnaami M., Alokail M., McTernan F. Effects of a multi-strain probiotic supplement for 12 weeks in circulating endotoxin levels and cardiometabolic profiles of medication naïve T2DM patients: A randomized clinical trial. J. Transl. Med. 2017;15:249. doi: 10.1186/s12967-017-1354-x.
    1. Cani P.D. Gut microbiota and obesity: Lessons from the microbiome. Brief Funct. Genom. 2013;12:381–387. doi: 10.1093/bfgp/elt014.
    1. Bindels L.B., Dewulf E.M., Delzenne N.M. GPR43/FFA2: Physiopathological relevance and therapeutic prospects. Trends Pharmacol. Sci. 2013;34:226–232. doi: 10.1016/j.tips.2013.02.002.
    1. Takemura N., Okubo T., Sonoyama K. Lactobacillus plantarum strain No. 14 reduces adipocyte size in mice fed high-fat diet. Exp. Biol. Med. 2010;235:849–856. doi: 10.1258/ebm.2010.009377.
    1. Kang J.H., Yun S.I., Park H.O. Effects of Lactobacillus gasseri BNR17 on body weight and adipose tissue mass in diet-induced overweight rats. J. Microbiol. 2010;48:712–714. doi: 10.1007/s12275-010-0363-8.
    1. Lee H.Y., Park J.H., Seok S.H., Baek M.W., Kim D.J., Lee K.E., Paek K.S., Lee Y., Park J.H. Human originated bacteria, Lactobacillus rhamnosus PL60, produce conjugated linoleic acid and show anti-obesity effects in diet-induced obese mice. Biochim. Biophys. Acta. 2006;1761:736–744. doi: 10.1016/j.bbalip.2006.05.007.
    1. Hamad E.M., Sato M., Uzu K., Yoshida T., Higashi S., Kawakami H., Kadooka Y., Matsuyama H., Abd El-Gawad I.A., Imaizumi K. Milk fermented by Lactobacillus gasseri SBT2055 influences adipocyte size via inhibition of dietary fat absorption in Zucker rats. Br. J. Nutr. 2009;101:716–724. doi: 10.1017/S0007114508043808.
    1. Miyoshi M., Ogawa A., Higurashi S., Kadooka Y. Anti-obesity effect of Lactobacillus gasseri SBT2055 accompanied by inhibition of pro-inflammatory gene expression in the visceral adipose tissue in diet-induced obese mice. Eur. J. Nutr. 2014;53:599–606. doi: 10.1007/s00394-013-0568-9.
    1. Chen Z., Guo L., Zhang Y., Walzem R.L., Pendergast J.S., Printz R.L., Morris L.C., Matafonova E., Stien X., Kang L., et al. Incorporation of therapeutically modified bacteria into gut microbiota inhibits obesity. J. Clin. Investig. 2014;124:3391–3406. doi: 10.1172/JCI72517.
    1. Borgeraas H., Johnson L.K., Skattebu J., Hertel J.K., Hjelmesaeth J. Effects of probiotics on body weight, body mass index, fat mass and fat percentage in subjects with overweight or obesity: A systematic review and meta-analysis of randomized controlled trials. Obes. Rev. 2018;19:219–232. doi: 10.1111/obr.12626.
    1. Kumar R., Grover S., Batish V.K. Hypocholesterolemic effect of dietary inclusion of two putative probiotic bile salt hydrolase-producing Lactobacillus plantarum strains in Sprague-Dawley rats. Br. J. Nutr. 2011;105:561–573. doi: 10.1017/S0007114510003740.
    1. Ejtahed H.S., Mohtadi-Nia J., Homayouni-Rad A., Niafar M. Effect of probiotic yogurt containing Lactobacillus acidophilus and Bifidobacterium lactis on lipid profile in individuals with type 2 diabetes mellitus. J. Dairy Sci. 2011;94:3288–3294. doi: 10.3168/jds.2010-4128.
    1. Asemi Z., Zare Z., Shakeri H., Sabihi S., Esmaillzadeh A. Effect of multispecies probiotic supplements on metabolic profile, hs-CRP, and oxidative stress in patients with type 2 diabetes. Ann. Nutr. Metab. 2013;63:631–639. doi: 10.1159/000349922.
    1. Fukushima M., Yamada A., Endo T., Nakano M. Effects of a mixture of organisms, Lactobacillus acidophilus or Streptococcus faecalis on delta6-desaturase activity in the livers of rats fed a fat- and cholesterol-enriched diet. Nutrition. 1999;15:373–378. doi: 10.1016/S0899-9007(99)00030-1.
    1. Shimizu M., Hashiguchi M., Shiga T., Tamura H.O., Mochizuki M. Meta-Analysis: Effects of Probiotic Supplementation on Lipid Profiles in Normal to Mildly Hypercholesterolemic Individuals. PLoS ONE. 2015;10:e0139795. doi: 10.1371/journal.pone.0139795.
    1. Honda K., Saneyasu T., Hasegawa S., Tominaga Y., Yokota S., Kamisoyama H. Effect of licorice flavonoid oil on cholesterol metabolism in high-fat diet rats. Biosci. Biotechnol. Biochem. 2013;77:1326–1328. doi: 10.1271/bbb.130104.
    1. Yadav H., Jain S., Sinha P.R. Antidiabetic effect of probiotic dahi containing Lactobacillus acidophilus and Lactobacillus casei in high fructose-fed rats. Nutrition. 2007;23:62–68. doi: 10.1016/j.nut.2006.09.002.
    1. Cani P.D., Neyrinck A.M., Fava F., Knaus C., Burcelin R.G., Tuohy K.M. Selective increases of bifidobacteria in gut microflora improve high-fat diet-induced diabetes in mice through the mechanism associated with endotoxemia. Diabetologia. 2007;50:2374–2383. doi: 10.1007/s00125-007-0791-0.
    1. Everard A., Belzer C., Geurts L., Ouwerkerk J.P., Druart C., Bindels L.B., Guiot Y., Derrien M., Muccioli G.G., Delzenne N.M., et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc. Natl. Acad. Sci. USA. 2013;110:9066–9071. doi: 10.1073/pnas.1219451110.
    1. Li M., Yang D., Mei L., Yuan L., Xie A., Yuan J. Screening and Characterization of Purine Nucleoside Degrading Lactic Acid Bacteria Isolated from Chinese Sauerkraut and Evaluation of the Serum Uric Acid Lowering Effect in Hyperuricemic Rats. PLoS ONE. 2014;9:e105577. doi: 10.1371/journal.pone.0105577.
    1. Dehghani H., Heidari F., Mozaffari-Khosravi H., Nouri-Majelan N., Dehghani A. Synbiotic Supplementations for Azotemia in Patients with Chronic Kidney Disease: A Randomized Controlled Trial. Iran. J. Kidney Dis. 2016;10:351–357.
    1. Hashem M.A., Mohamed M.H. Haemato-biochemical and pathological studies on aflatoxicosis and treatment of broiler chicks in Egypt. Vet. Ital. 2009;45:323–337.
    1. Brun P., Castigaliuolo I., Leo V.D., Buda A., Pinzani M., Palu G., Martines D. Increased intestinal permeability in obese mice: New evidence in the pathogenesis of nonalcoholic steatohepatitis. Am. J. Physiol. Gastrointest. Liver Physiol. 2007;292:G518–G525. doi: 10.1152/ajpgi.00024.2006.
    1. Le Barz M., Anhe F.F., Varin T.C., Desjardins Y., Levy E., Roy D., Urdaci M.C., Marette A. Probiotics as complementary treatment for metabolic disorders. Diabetes Metab. J. 2015;39:291–303. doi: 10.4093/dmj.2015.39.4.291.

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