Effects of probiotic intervention on obesity-related miRNAs

  • Nina Okuka University of Banja Luka, Faculty of Medicine, Department of Bromatology
  • Berit Hippe University of Vienna, Department of Nutritional Science
  • Brižita Djordjević University of Belgrade – Faculty of Pharmacy, Department of Bromatology
  • Nevena Ivanović University of Belgrade – Faculty of Pharmacy, Department of Bromatology
Keywords: obesity, microRNA, probiotics

Abstract


Obesity is considered to be a chronic complex disease that increases the risk of diabetes, heart diseases and certain cancers. According to the literature, in obese people the gastrointestinal microbiota is disturbed, which could be the cause of the onset of obesity and related diseases. Moreover, there are small non-coding RNAs (microRNAs) that are disturbed in obesity, which are also considered to be a possible mechanism of probiotics’ action. Certain microRNAs are involved in the development and metabolism of adipose tissue cells, as well as the secretion and action of insulin, showing that changed expression of certain miRNAs could have a significant impact on the onset and development of obesity and obesity-related diseases. Thus, miRNAs are considered to be possible markers for the diagnosis and prognosis of various metabolic diseases, and possible therapeutic targets for the treatment of obesity and related diseases. Considering the growing need of the healthcare system for nutraceuticals and dietary supplements that present effective and safe medical nutritive therapy in obese individuals, this work aimed to assess the beneficial effects of probiotics on obesity-related microRNAs. In this review, we described the role of microRNAs and probiotics in obesity and the association between probiotics and obesity-related microRNAs. Circulating miRNAs’ profile in obese individuals significantly differs from that of normal-weight individuals. miRNAs such as miR-155, miR-221, miR-24-3p, and miR-181a are over-expressed, while miR-26b and 125a are under-expressed in obese patients compared to non-obese individuals. It has been found that supplementation with Bifidobacterium bifidum and Lactobacillus acidophilus could downregulate the expression of miR-155 and miR-221, and upregulate the expression of miR-26b. Supplementation with a probiotic formulation containing S. boulardii, L. plantarum 299v, and octacosanol led to the downregulation of miR-155 and miR-24-3p expression. miR-125a and miR-181a were upregulated and downregulated, respectively, after the intervention with L. delbrueckii and L. rhamnosus. After reviewing the available literature, we can conclude that probiotics have beneficial effects on microRNAs altered in obesity, which could provide an effective strategy for the management of obesity.

References

WHO European regional obesity report 2022: World Health Organization. Regional Office for Europe; 2022.

Haththotuwa RN, Wijeyaratne CN, Senarath U. Worldwide epidemic of obesity. In: Mahmood TA, Arulkumaran S, Chervenak FA, editors. Obesity and obstetrics. Elsevier; 2020; p. 3-8.

Michaličkova D. Uticaj suplementacije sojem Lactobacillus helveticus L10 na markere imunskog i oksidativnog statusa vrhunskih sportista [dissertation]. [Beograd]: Univerzitet u Beogradu; 2017.

DeGruttola AK, Low D, Mizoguchi A, Mizoguchi E. Current understanding of dysbiosis in disease in human and animal models. Inflamm Bowel Dis. 2016;22(5):1137-50.

Geng J, Ni Q, Sun W, Li L, Feng X. The links between gut microbiota and obesity and obesity related diseases. Biomed Pharmacother. 2022;147:112678.

Graham C, Mullen A, Whelan K. Obesity and the gastrointestinal microbiota: a review of associations and mechanisms. Nutr Rev. 2015;73(6):376-85.

Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444(7122):1027-31.

Blaut M. Gut microbiota and energy balance: role in obesity. Proc Nutr Soc. 2015;74(3):227-34.

Amabebe E, Robert FO, Agbalalah T, Orubu ES. Microbial dysbiosis-induced obesity: role of gut microbiota in homoeostasis of energy metabolism. Br J Nutr. 2020;123(10):1127-37.

Cerdó T, García-Santos JA, G. Bermúdez M, Campoy C. The role of probiotics and prebiotics in the prevention and treatment of obesity. Nutrients. 2019;11(3):635.

Vähämiko S, Laiho A, Lund R, Isolauri E, Salminen S, Laitinen K. The impact of probiotic supplementation during pregnancy on DNA methylation of obesity-related genes in mothers and their children. Eur J Nutr. 2019;58:367-77.

Liu T, Song X, An Y, Wu X, Zhang W, Li J, et al. Lactobacillus rhamnosus GG colonization in early life ameliorates inflammaging of offspring by activating SIRT1/AMPK/PGC-1α pathway. Oxid Med Cell Longev. 2021;2021:3328505.

Cani PD, Van Hul M. Novel opportunities for next-generation probiotics targeting metabolic syndrome. Curr Op Biotechnol. 2015;32:21-7.

Livingstone KM, Ramos-Lopez O, Perusse L, Kato H, Ordovas JM, Martínez JA. Precision nutrition: A review of current approaches and future endeavors. Trends Food Sci Technol. 2022;128:253-264.

Morelli L, Capurso L. FAO/WHO guidelines on probiotics: 10 years later. J Clin Gastroenterol. 2012;46:S1-S2.

Stojanov S, Berlec A, Štrukelj B. The influence of probiotics on the firmicutes/bacteroidetes ratio in the treatment of obesity and inflammatory bowel disease. Microorganisms. 2020;8(11):1715.

Portincasa P, Bonfrate L, Khalil M, Angelis MD, Calabrese FM, D’amato M, et al. Intestinal barrier and permeability in health, obesity and NAFLD. Biomedicines. 2021;10(1):83.

Wiciński M, Gębalski J, Gołębiewski J, Malinowski B. Probiotics for the treatment of overweight and obesity in humans—a review of clinical trials. Microorganisms. 2020;8(8):1148.

Arora T, Singh S, Sharma RK. Probiotics: interaction with gut microbiome and antiobesity potential. Nutrition. 2013;29(4):591-6.

Garcia-Gonzalez N, Battista N, Prete R, Corsetti A. Health-promoting role of Lactiplantibacillus plantarum isolated from fermented foods. Microorganisms. 2021;9(2):349.

Mazloom Z, Yousefinejad A, Dabbaghmanesh MH. Effect of probiotics on lipid profile, glycemic control, insulin action, oxidative stress, and inflammatory markers in patients with type 2 diabetes: a clinical trial. Iran J Med Sci. 2013;38(1):38.

Rouxinol-Dias AL, Pinto AR, Janeiro C, Rodrigues D, Moreira M, Dias J, et al. Probiotics for the control of obesity–Its effect on weight change. Porto Biomed J. 2016;1(1):12-24.

Wang Q, Sun Q, Wang J, Qiu X, Qi R, Huang J. Lactobacillus plantarum 299v changes miRNA expression in the intestines of piglets and leads to downregulation of LITAF by regulating ssc-miR-450a. Probiotics Antimicrob Proteins. 2021;13(4):1093-105.

Zhao Y, Zeng Y, Zeng D, Wang H, Zhou M, Sun N, et al. Probiotics and MicroRNA: their roles in the host–microbe interactions. Front Microbiol. 2021;11:604462.

Ibarra PE, García-Solís P, Solís-Sáinz JC, Cruz-Hernández A. Expression of miRNA in obesity and insulin resistance: a review. Endokrynol Pol. 2021;72(1):73-80.

Iacomino G, Siani A. Role of microRNAs in obesity and obesity-related diseases. Genes Nutr. 2017;12:1-16.

O'Brien J, Hayder H, Zayed Y, Peng C. Overview of microRNA biogenesis, mechanisms of actions, and circulation. Front Endocrinol. 2018;9:388354.

Sacco LD, Masotti A. Recent insights and novel bioinformatics tools to understand the role of microRNAs binding to 5'untranslated region. Int J Mol Sci. 2013;14(1):480-95.

Dumortier O, Hinault C, Van Obberghen E. MicroRNAs and metabolism crosstalk in energy homeostasis. Cell Metab. 2013;18(3):312-24.

Ji C, Guo X. The clinical potential of circulating microRNAs in obesity. Nat Rev Endocrinol. 2019;15(12):731-43.

Landrier J-F, Derghal A, Mounien L. MicroRNAs in obesity and related metabolic disorders. Cells. 2019;8(8):859.

Heneghan H, Miller N, McAnena O, O'brien T, Kerin M. Differential miRNA expression in omental adipose tissue and in the circulation of obese patients identifies novel metabolic biomarkers. J Clin Endocrinol Metab. 2011;96(5):E846-E50.

Pointner A, Krammer UD, Tomeva E, Magnet U, Hippe B, Jacob U, et al. Lifestyle-Driven Variations in Nutrimiromic MicroRNA Expression Patterns across and beyond Genders. Life. 2024;14(3):390.

Díez-Sainz E, Lorente-Cebrián S, Aranaz P, Riezu-Boj JI, Martínez JA, Milagro FI. Potential mechanisms linking food-derived microRNAs, gut microbiota and intestinal barrier functions in the context of nutrition and human health. Front Nutr. 2021;8:586564.

Jia M, He J, Bai W, Lin Q, Deng J, Li W, et al. Cross-kingdom regulation by dietary plant miRNAs: an evidence-based review with recent updates. Food Funct. 2021;12(20):9549-62.

del Pozo‐Acebo L, López de las Hazas MC, Margollés A, Dávalos A, García‐Ruiz A. Eating microRNAs: pharmacological opportunities for cross‐kingdom regulation and implications in host gene and gut microbiota modulation. Br J Pharmacol. 2021;178(11):2218-45.

Liu S, Rezende RM, Moreira TG, Tankou SK, Cox LM, Wu M, et al. Oral administration of miR-30d from feces of MS patients suppresses MS-like symptoms in mice by expanding Akkermansia muciniphila. Cell Host Microbe. 2019;26(6):779-94.e8.

Greenberg AS, Obin MS. Obesity and the role of adipose tissue in inflammation and metabolism. American J Clin Nutr. 2006;83(2):461S-5S.

Martins LM, Oliveira ARS, Cruz KJC, Torres-Leal FL, Marreiro DdN. Obesity, inflammation, and insulin resistance. Braz J Pharm Sci. 2014;50:677-92.

Karczewski J, Śledzińska E, Baturo A, Jończyk I, Maleszko A, Samborski P, et al. Obesity and inflammation. Eur Cytokine Netw. 2018;29:83-94.

Tryggestad JB, Teague AM, Sparling DP, Jiang S, Chernausek SD. Macrophage‐derived microRNA‐155 increases in obesity and influences adipocyte metabolism by targeting peroxisome proliferator‐activated receptor gamma. Obesity. 2019;27(11):1856-64.

Mahdavi R, Ghorbani S, Alipoor B, Panahi G, Khodabandehloo H, Esfahani EN, et al. Decreased serum level of miR-155 is associated with obesity and its related metabolic traits. Clin Lab. 2018;64:77-84.

Lopez YON, Garufi G, Seyhan AA. Altered levels of circulating cytokines and microRNAs in lean and obese individuals with prediabetes and type 2 diabetes. Mol Biosyst. 2017;13(1):106-21.

Karkeni E, Astier J, Tourniaire F, El Abed M, Romier B, Gouranton E, et al. Obesity-associated inflammation induces microRNA-155 expression in adipocytes and adipose tissue: outcome on adipocyte function. J Clin Endocrinol Metab. 2016;101(4):1615-26.

Huang G, Hao F, Hu X. Downregulation of microRNA‐155 stimulates sevoflurane‐mediated cardioprotection against myocardial ischemia/reperfusion injury by binding to SIRT1 in mice. J Cell Biochem. 2019;120(9):15494-505.

Yang N, Cheng H, Mo Q, Zhou X, Xie M. miR‑155‑5p downregulation inhibits epithelial‑to‑mesenchymal transition by targeting SIRT1 in human nasal epithelial cells. Mol Med Rep. 2020;22(5):3695-704.

Wang X, Gao Y, Yi W, Qiao Y, Hu H, Wang Y, et al. Inhibition of miRNA-155 alleviates high glucose-induced podocyte inflammation by targeting SIRT1 in diabetic mice. J Diabetes Res. 2021;2021:1-11.

Zhong Y, Lee K, He JC. SIRT1 is a potential drug target for treatment of diabetic kidney disease. Front Endocrinol. 2018;9:412179.

Virtue A, Johnson C, Lopez-Pastraña J, Shao Y, Fu H, Li X, et al. MicroRNA-155 deficiency leads to decreased atherosclerosis, increased white adipose tissue obesity, and non-alcoholic fatty liver disease: a novel mouse model of obesity paradox. J Biol Chem. 2017;292(4):1267-87.

Algieri F, Garrido-Mesa J, Vezza T, Rodríguez-Sojo MJ, Rodríguez-Cabezas ME, Olivares M, et al. Intestinal anti-inflammatory effects of probiotics in DNBS-colitis via modulation of gut microbiota and microRNAs. Eur J Nutr. 2021;60:2537-51.

Heydari Z, Rahaie M, Alizadeh AM, Agah S, Khalighfard S, Bahmani S. Effects of Lactobacillus acidophilus and Bifidobacterium bifidum probiotics on the expression of microRNAs 135b, 26b, 18a and 155, and their involving genes in mice colon cancer. Probiotics Antimicrob Proteins. 2019;11:1155-62.

Okuka N, Schuh V, Krammer U, Polovina S, Sumarac-Dumanovic M, Milinkovic N, et al. Epigenetic Aspects of a New Probiotic Concept—A Pilot Study. Life. 2023;13(9):1912.

Ng R, Wu H, Xiao H, Chen X, Willenbring H, Steer CJ, et al. Inhibition of microRNA‐24 expression in liver prevents hepatic lipid accumulation and hyperlipidemia. Hepatology. 2014;60(2):554-64.

Nunez Lopez YO, Garufi G, Pasarica M, Seyhan AA. Elevated and correlated expressions of miR-24, miR-30d, miR-146a, and SFRP-4 in human abdominal adipose tissue play a role in adiposity and insulin resistance. Int J Endocrinol. 2018;2018:7351902.

Jeon TI, Osborne TF. miRNA and cholesterol homeostasis. Biochim Biophys Acta. 2016;1861(12):2041-6.

Garavelli S, Bruzzaniti S, Tagliabue E, Di Silvestre D, Prattichizzo F, Mozzillo E, et al. Plasma circulating miR-23~ 27~ 24 clusters correlate with the immunometabolic derangement and predict C-peptide loss in children with type 1 diabetes. Diabetologia. 2020;63:2699-712.

Zhang B, Xing L, Wang B. Dysregulation of circulating miR-24-3p in children with obesity and its predictive value for metabolic syndrome. Obes Facts. 2021;14(5):456-62.

Ren K, Zhu X, Zheng Z, Mo Z-C, Peng X-S, Zeng Y-Z, et al. MicroRNA-24 aggravates atherosclerosis by inhibiting selective lipid uptake from HDL cholesterol via the post-transcriptional repression of scavenger receptor class B type I. Atherosclerosis. 2018;270:57-67.

Arner P, Kulyté A. MicroRNA regulatory networks in human adipose tissue and obesity. Nat Rev Endocrinol. 2015;11(5):276-88.

Xie H, Lim B, Lodish HF. MicroRNAs induced during adipogenesis that accelerate fat cell development are downregulated in obesity. Diabetes. 2009;58(5):1050-7.

Chou W-W, Wang Y-T, Liao Y-C, Chuang S-C, Wang S-N, Juo S-HH. Decreased microRNA-221 is associated with high levels of TNF-α in human adipose tissue-derived mesenchymal stem cells from obese woman. Cell Physiol Biochem. 2013;32(1):127-37.

Meerson A, Traurig M, Ossowski V, Fleming J, Mullins M, Baier L. Human adipose microRNA-221 is upregulated in obesity and affects fat metabolism downstream of leptin and TNF-α. Diabetologia. 2013;56:1971-9.

Heydari Z, Rahaie M, Alizadeh AM. Different anti-inflammatory effects of Lactobacillus acidophilus and Bifidobactrum bifidioum in hepatocellular carcinoma cancer mouse through impact on microRNAs and their target genes. J Nutrition Intermed Metab. 2019;16:100096.

Saffar KN, Larypoor M, Torbati MB. Analyzing of colorectal cancerrelated genes and microRNAs expression profiles in response to probiotics Lactobacillus acidophilus and Saccharomyces cerevisiae in colon cancer cell lines. Mol Biol Rep. 2024;51(1):122.

Benderska N, Dittrich A-L, Knaup S, Rau TT, Neufert C, Wach S, et al. miRNA-26b overexpression in ulcerative colitis-associated carcinogenesis. Inflamm Bowel Dis. 2015;21(9):2039-51.

Cristóbal I, Manso R, Gónzález-Alonso P, Madoz-Gúrpide J, Rojo F, García-Foncillas J. Clinical Value of miR-26b Discriminating Ulcerative Colitis–associated Colorectal Cancer in the Subgroup of Patients with Metastatic Disease. Inflamm Bowel Dis. 2015;21(10):E24-E5.

Liu H, Chu W, Gong L, Gao X, Wang W. MicroRNA‑26b is upregulated in a double transgenic mouse model of Alzheimer's disease and promotes the expression of amyloid‑β by targeting insulin‑like growth factor 1. Mol Med Rep. 2016;13(3):2809-14.

Karbiener M, Pisani DF, Frontini A, Oberreiter LM, Lang E, Vegiopoulos A, et al. MicroRNA-26 family is required for human adipogenesis and drives characteristics of brown adipocytes. Stem Cells. 2014;32(6):1578-90.

Xu G, Ji C, Song G, Zhao C, Shi C, Song L, et al. MiR-26b modulates insulin sensitivity in adipocytes by interrupting the PTEN/PI3K/AKT pathway. Int J Obes. 2015;39(10):1523-30.

Fu X, Dong B, Tian Y, Lefebvre P, Meng Z, Wang X, et al. MicroRNA-26a regulates insulin sensitivity and metabolism of glucose and lipids. J Clin Invest. 2015;125(6):2497-509.

Acharya A, Berry DC, Zhang H, Jiang Y, Jones BT, Hammer RE, et al. miR-26 suppresses adipocyte progenitor differentiation and fat production by targeting Fbxl19. Genes Dev. 2019;33(19-20):1367-80.

Xu G, Ji C, Shi C, Fu H, Zhu L, Zhu L, et al. Modulation of hsa-miR-26b levels following adipokine stimulation. Mol Biol Rep. 2013;40:3577-82.

Ortiz-Dosal A, Rodil-Garcia P, Salazar-Olivo LA. Circulating microRNAs in human obesity: a systematic review. Biomarkers. 2019;24(6):499-509.

Rockstroh D, Löffler D, Kiess W, Landgraf K, Körner A. Regulation of human adipogenesis by miR125b-5p. Adipocyte. 2016;5(3):283-97.

Brandao BB, Guerra BA, Mori MA. Shortcuts to a functional adipose tissue: The role of small non-coding RNAs. Redox Biol. 2017;12:82-102.

Ortega FJ, Mercader JM, Moreno-Navarrete JM, Rovira O, Guerra E, Esteve E, et al. Profiling of circulating microRNAs reveals common microRNAs linked to type 2 diabetes that change with insulin sensitization. Diabetes Care. 2014;37(5):1375-83.

Ortega FJ, Mercader JM, Catalan V, Moreno-Navarrete JM, Pueyo N, Sabater M, et al. Targeting the circulating microRNA signature of obesity. Clin Chem. 2013;59(5):781-92.

Xu L, Li Y, Yin L, Qi Y, Sun H, Sun P, et al. miR-125a-5p ameliorates hepatic glycolipid metabolism disorder in type 2 diabetes mellitus through targeting of STAT3. Theranostics. 2018;8(20):5593.

Vahidi Z, Saghi E, Mahmoudi M, RezaieYazdi Z, Esmaeili S-A, Zemorshidi F, et al. Lactobacillus rhamnosus and Lactobacillus delbrueckii Ameliorate the Expression of miR-125a and miR-146a in Systemic Lupus Erythematosus Patients. Appl Biochem Biotechnol. 2024. doi: 10.1007/s12010-023-04827-w. Epub ahead of print. PMID: 38351428.

Williams A, Henao-Mejia J, Harman CC, Flavell RA. miR-181 and metabolic regulation in the immune system. Cold Spring Harb Symp Quant Biol. 2013;78:223-30.

Vahidi Z, Samadi M, Mahmoudi M, RezaieYazdi Z, Sahebari M, Tabasi N, et al. Lactobacillus rhamnosus and Lactobacillus delbrueckii ameliorate the expression of miR-155 and miR-181a in SLE patients. J Funct Foods. 2018;48:228-33.

Virtue AT, McCright SJ, Wright JM, Jimenez MT, Mowel WK, Kotzin JJ, et al. The gut microbiota regulates white adipose tissue inflammation and obesity via a family of microRNAs. Sci Transl Med. 2019;11(496):eaav1892.

Published
2024/06/28
Section
Review articles