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Posted on Authorea 23 Jul 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159551303.38968103 — This a preprint and has not been peer reviewed. Data may be preliminary. odto sdvlpda osqec fa nryiblnedet necsieeeg naeand intake energy excessive an to due This imbalance 2018). energy Calder, an & 2010). of (Rogero Zimmet, syndrome consequence worldwide & metabolic a the of Grundy hypertension, as of axis obesity, Alberti, central developed 25% resistance, the (Eckel, is affects considered insulin dyslipidemia condition It is including and obesity dysfunctions them, time. hyperglycemia Among metabolic our tolerance, several characterized of glucose is of syndrome problems impaired Metabolic concurrence health 2018). (Saklayen, the public increasing constantly by the is prevalence of its and one population, is syndrome Metabolic tolerated. well ameliorate and INTRODUCTION safe to role relatively of key be this use to a potential demonstrated of play have a to ability treatments suggests reported the probiotic this been that time, Therefore, account have first into that obesity. taking the of for different pathogenesis affecting describe, the modulation, findings in microbiome Our through obesity approach. experimental interesting very a represents restores probiotic The and dysbiosis. gut and dysfunction endothelial Garcia Molina-Tijeras Alberto Jose gut of dysbiosis. modulation microbiota through mice in fat obesity high diet-induced ameliorates CECT5716 fermentum niiflmaoyeet n aaiyt ouaemcoit opsto ndffrn xeietlmodels. experimental different this mice. in management. on composition obesity effects microbiota for beneficial modulate treatments. strategies demonstrated Approach: to probiotic have and safer capacity of effectiveness and and development Different implies limited effective effects the therapy. disease more anti-inflammatory present in promising interest such for a them the as demand of of increasing emerging urgent management most condition, are an Unfortunately, probiotics its is sense, Nowadays, there this drugs. Therefore In anti-obesity dysfunctions. effects. different metabolic side and related important lifestyle the in of changes development drastic the to contribute Purpose: and Background Abstract 2020 23, July Granada of University 4 3 2 Granada of University 1 Rodriguez-Cabezas Elena Maria I˜naki Robles-Vera IE-H,Dprmn fPamclg,Cne o imdclRsac (CIBM), Research Biomedical for Center Pharmacology, of Department CIBER-EHD, 1 Life (ibs.GRANADA) Biosearch Granada de Investigaci´on Biosanitaria de (CIBM), Instituto Research Biomedical for Center Pharmacology, of Department CIBER-EHD, lsrdu spp Clostridium e results: Key 1 noi Jes´us Ruiz-Malag´on Antonio , .fermentum L. .fermentum L. rsnea ela increased as well as presence 2 eeioGarcia Federico , ET76(5x10 CECT5716 bst sacmlxcniinweealwgaecrnciflmainadgtdysbiosis gut and inflammation chronic low-grade a where condition complex a is Obesity xrsat-bst ffcs soitdwt t niiflmaoypoete n amelioration and properties anti-inflammatory its with associated effects, anti-obesity exerts 1 arcaDiez-Echave Patricia , 1 laRodr´ıguez-Nogales Alba , 8 F/iedy a vlae namdlo ihftde-nue bst in obesity diet-induced fat high of model a in evaluated was CFU/mice/day) 2 ui Plaza-Diaz Julio , Bacteroides 1 ai Jes´us Rodr´ıguez-Sojo Maria , 1 proportion. Akkermansia 1 eeaVezza Teresa , .fermentum L. 2 M´onica Olivares , ocuinadImplications: and Conclusion atbclu fermentum Lactobacillus p bnac n reduced and abundance sp. 4 n ui Galvez Julio and , ET76i lnclpatc,also practice, clinical in CECT5716 1 ar Hidalgo Laura , 1 iulRomero Miguel , 3 unDuarte Juan , ET76hsshown has CECT5716 Erysipelotrichi 1 Experimental hsprobiotic This 2 , 2 class , Posted on Authorea 23 Jul 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159551303.38968103 — This a preprint and has not been peer reviewed. Data may be preliminary. 09.Frhroe hs tde ihih h blt fti rboi oaeirt u irboadysbio- microbiota gut ameliorate to al., probiotic et Toral this 2018; of al., ability et (Rodriguez- the (Robles-Vera colitis highlight & hypertension of studies and models Morris these experimental 2015) Furthermore, (Bond, in al., 2019). Rodr´ıguez-Nogales mothers obtained et 2017; effects and al., beneficial infants the et in in interest-Nogales involved tolerance be an and can safety be that interest. proven properties of can with be syndrome could 2003) 2017), metabolic al., Nassar, et for characterization (Martin tested the context, milk Meanwhile, previously breast this 2017). not In Wiele, strains, approach. development de their probiotic ing Van hinder conventional & can Hernandez-Sanabria other limitations Hage, regulatory of (El and technological therapy However, human generation 2019). for next including al., emerging et conditions, for (Chang the these treatments others these, against probiotic-based Among new studied of be safety. search minuta to and the started in efficacy interest have combine just great probiotics that syndrome a the syndrome is and metabolic there Gomez- metabolic profile with & reason, human metabolic Gil this patients the For Martinez-Ramirez, clinical (Tenorio-Jimenez, on to 2020). randomized condition impact Llorente, probiotics this of their with of considering review associated com- when administration biomarkers systematic especially inflammatory microbiota recent date, improvement, gut discrete a to a of However, up produces modulation 2020). that, through Abdollahi, concluded probably & trials and most metabolism Nikfar beneficial acid endotoxemia, (Daniali, bile their metabolic (Tenorio-Jimenez, of position in regulation resistance from involved production, insulin (SCFA) be protection acid may decreasing host fatty mechanisms short-chain as Different increased well weight including 2020). as modulating effects, Gomez-Llorente, by metabolism, & humans, lipid Gil and and Martinez-Ramirez, rodents in glycemic both improving administered effects, gain, when anti-obesity considerable host probiotics, demonstrating the Among drome, to benefit 2004). health (mainly al., a et confer (LAB13) (Backhed that rota amounts adequate live re- as in and defined disorders Gomez-Llorente, are & metabolic Probiotics Gil obesity-associated Martinez-Ramirez, (Tenorio-Jimenez, of paid explored treatment recently be and function in should been prevention barrier attention has 2020). involved the special it intestinal mechanisms for context, as the this diseases, pathogenic probiotics of In lated of the enhancement 2016). use Terra, of and the & Considering amelioration response to Blay Ardevol, in inflammatory 2012). Pinent, result the al., Gines, the (Gil-Cardoso, of can et to Teixeira modulation microbiota contributes 2007; like gut translo- clearly obesity, al., of endotoxins which also et bacterial modulation circulation, composition, (Cani promotes systemic microbiota this, inflammation that intestinal the systemic permeability altered into low-grade Marasco, an gut (LPS), obesity-associated Eusebi, to increased lipopolysaccharide Schiumerini, linked with including its (Festi, been important together cation, for disorders an has dysbiosis, play strategies Obesity obesity-associated as to and safer seems known 2014). microbiota obesity and Colecchia, gut of effective & that development Taddia revealed more have the studies for in different demand decades, role prevalence last clear two the side a the considering During significant is and and there Therefore, the effectiveness co-morbidities, Nowadays, 2018). limited its Aronne, orlistat, present management. 2010). and phentermine, & them are Choue, obesity Kumar of used & Igel, of most frequently Umashanker, Shin but most (Saunders, Lee, The liraglutide, effects 2019; available. exercise. and and are Kim, bupropion restrictions drugs dietary & lorcaserin, including anti-obesity lifestyle, Jang different in the addition, changes Oh, drastic diseases in In Kim, implies obesity-related usually results and Han, obesity dysfunctions This of metabolic (Jang, management the patients to 2014). contributes these (TNF)- pro-inflammatory Paquot, and factor in of tissues & necrosis secretion adipose tumor Scheen to the and macrophages tissue with Piette, of (IL)-6 adipose associated interleukin Legrand-Poels, mainly state, as inflammatory tissues, Esser, such systemic mediators, metabolic 2010; low-grade in a al., lipids of et of development accumulation (Ding abnormal liver an and to leading expenditure, low , .infantis B. aaatrie goldsteinii Parabacteroides , .gasseri L. , .longum B. , .rhamnosus L. .fermentum L. and , .fermentum L. .beeB3 breve B. , kemni muciniphila Akkermansia and , ET76 rboi tanoiial sltdfo human from isolated originally strain probiotic a CECT5716, ET76hsbe hw odslyimmunomodulatory display to shown been has CECT5716 r h otrlvn nteteteto eaoi syn- metabolic of treatment the in relevant most the are ) .plantarum L. 2 mn tes and others) among , or atbclu spp. Lactobacillus atrie thetaiotaomicron Bacteroides α. hs tpooe h recruitment the promotes it Thus, rvtlacopri Prevotella ( idbceimspp. Bifidobacterium .csisri Shi- strain casei L. , Christensenella among , Posted on Authorea 23 Jul 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159551303.38968103 — This a preprint and has not been peer reviewed. Data may be preliminary. is(pnec,SA,Grn,San.Pam nui ocnrtoswr unie sn os insulin (HOMA- mouse resistance a insulin of using assessment quantified model were Homeostatic USA). concentrations NH, insulin col- Salem, Spinreact Plasma Diagnosis, were using (Alpco Spain). samples 4 methods kit ELISA lipoprotein colorimetric Girona, at Blood high-density by S.A., g (LDL)-cholesterol, measured (Spinreact, 5000 anesthesia. were lipoprotein kits concentrations low-density at isoflurane triglycerides glucose, centrifuged under and Plasma and (HDL)-cholesterol sacrificed -80degC. heparin were at containing frozen mice measured tubes was was treatment, ice-cold glucose the in Blood of lected injection. end blood after the and min Spain). injection, At 120 Barcelona, intraperitoneal S.L., and by Care, weight determinations 60 received Diabetes Plasma They body 30, Ascensia of 15, 2.4.2. h. 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(HFD)-induced al., of et strains (Tomaro-Duchesneau difficult metabolism other lipid Furthermore, being administration. synbiotic, probiotic of a from tration as derived fructooligosaccharides were fermentum effects with L. which administered establish was effects clearly probiotic anti-obesity to (Fasano, the the syndrome Noteworthy, although 2014). metabolic 2017), Colecchia, of & features Taddia common Marasco, function, of Eusebi, barrier Schiumerini, intestinal Festi, impaired 2017; the improve and sis n .fermentum L. 1) oto cnrlde) bs HD n bs rae ( treated obese and (HFD) obese diet), (control control =10): .fermentum L. .fermentum L. 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Data may be preliminary. fteaioie etnadaioetni a ise ncmiainwt eue xrsino leptin of expression expression reduced the a restored significantly with treatment combination probiotic The in expression imbalance 4). tissue, (Figure an fat tissues in fat in resulted and intake adiponectin liver HFD both and in mice, leptin receptor diet-fed adipokines control with the comparison, of in and addition, In 3B). (Figure treatment the by with decreased treated a mice with HFD-fed of associated in was ameliorated mice were obese which in transporter metabolism glucose lipid the of and expression glucose in impairment the Furthermore, proliferator-activated peroxisome of expression expression altered its 3B). reduced an treatment manifested probiotic also whereas mice receptor group, obese diet the Likewise, control Likewise, 3A). the 3A). 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RESULTS Tlr4 .fermentum L. nlvradaioetsuswsas lee ncnrlHDfdmc,wihwssgicnl restored significantly was which mice, HFD-fed control in altered also was tissues adipose and liver in α ( .fermentum L. Ππαρα .fermentum L. 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Data may be preliminary. ffcsosre.Adtoal,i bs ainsdffrn hl aebe eotdt eicesd in- increased, be to reported beneficial been the have to phyla contribute different potentially patients and assimilation obese dysbiosis shift energy in obesity-associated a of of Additionally, cluding indicating amelioration reduction clusters, This the in the observed. probiotic. observed between with effects the values separation associated by normal clear induced be the a composition could showed to bacterial an analysis phyla showed gut PCA bacteria the mice However, The in main HFD-fed than non-digestible since the mice. food of mice. observations restoring diet-fed from hydrolysis these non-obese control composition, fat with efficient with microbiota and agrees more compared gut study calories when a modulate Our more ratio with extract 2004). 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Data may be preliminary. lHg ,HradzSnbi ,&Vnd il 21) mrigTed n”mr Probiotics”: in ”Smart Frontiers in Trends Applications. Emerging Industrial and (2017). Health T Novel Wiele of de Development 8 Van the microbiology 375 & lancet for The E, Consideration syndrome. Hernandez-Sanabria Functional metabolic R, The Hage (2010). PZ El Zimmet & SM, Grundy KG, Alberti RH, Eckel S 5 resistance Magness insulin one and NM, PloS obesity Schwerbrock with mouse. correlates R, and in precedes Rigby which Hypertension BP, inflammation intestinal Scull promote Hypertension. interactions MM, in Chi Inflammation S, of Ding Complexities web-based and a Role 45 MicrobiomeAnalyst: the research Unraveling 70 acids (2017). Nucleic (2017). J SP data. Xia Didion microbiome & of LB, meta-analysis Agellon and Africa. IL, visual 107 rural King W180-W188. statistical, America and S, comprehensive of Europe Habib for States from tool United J, S children the Chong Massart in of A, JB, study Sciences Dhariwal comparative Poullet of overweight a Academy M, treat National by Ramazzotti to the revealed M, probiotics of microbiota Paola of Proceedings gut Di use shaping the D, in 15 Cavalieri on diet metabolism overview C, & brief Filippo endocrinology A of De review (2020). Expert M Diet-Induced patients. Abdollahi obese of & Lactobacillus and Intestine S, of Effects Nikfar the Antiobesity 22 M, in (2019). food Daniali cloacae TH medicinal Enterobacter Kim of & of Journal YH, high- Inhibition Mice. Kim in by Obese HH, tissue Accompanied Jung HU, LMT1-48 adipose Jeong SP plantarum white HJ, Tsao Dong of 54 WJ, biochemistry CH, remodeling Choi nutritional Chan metabolism of Journal energy TY, The with Chien rats. associated KC, energy-diet-fed 263 Cheng reuteri YH, Lactobacillus Chen 27 CC LH, analysis Lu drug Chen WF, and Lai food TR, a Wu of YL, Journal obesity: Tsai amelioration. gastrointestinal with TL, of Lin adults journal CJ, World of Chang obesity. microbiota and gut microbiota between the link 6 of pathophysiology New-found Profile (2015). CK nutrition. (2020). clinical Chakraborti EL of LA, 29 journal Rosado NMCD Santos European & : review. Dos D, diseases systematic cardiovascular Carneiro Masterson and GAH, L, metabolism, Ferreira Crovesy Nutrition, MO, rats. diet-treated Freire fat Luna high in de TMR, M 2018 Albuquerque Magnani endocrinology de of journal RGS, STE International Cavalcante Shiow Review. F, Systematic Magkos SH, A D Lee Obesity: YM, Bastelica in Park C, A, Goday Knauf 56 O, M, Castaner Diabetes it Poggi resistance. Is MA, insulin and obesity: Iglesias obesity with J, initiates endotoxemia Amar Metabolic PD, 124 (2016). Cani Biochimie MW relevant? Hulver it trial. & Fer- is controlled MI, and Lactobacillus Frisard randomised real probiotic RP, a McMillan the women: NE, of breastfeeding evaluation Boutagy in 17 protocol: mastitis childbirth Study of and prevention pregnancy (2017). BMC the N for Nassar CECT5716 & mentum JM, Morris DM, biochemistry nutritional Bond of Journal The mice. DIO in sensitivity 50 insulin improve and microbiota gut modulate : : 700-702. 16-25. tal. et , : 1889. : 21) h rboi atbclu emnu 9 teutscrimtblcdisorders cardiometabolic attenuates 296 fermentum Lactobacillus probiotic The (2019). 110-119. : e12191. : 148. : 11-20. : 560-566. : : 1761-1772. 11 615-622. tal. et , 21) etgnrto rboisi disease in probiotics generation Next (2019). tal. et , : 87-94. tal. et , tal. et , tal. et , : 1-4. 21) h u irboeProfile Microbiome Gut The (2018). 20) eaoi endotoxemia Metabolic (2007). 21) ihftde:bacteria diet: High-fat (2010). 21) nibst ffc of effect Antiobesity (2018). : 4095789. tal. et , : 14691-14696. 21) matof Impact (2010). : 1408-1417. : 181-183. : Posted on Authorea 23 Jul 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159551303.38968103 — This a preprint and has not been peer reviewed. Data may be preliminary. i M en J o H a J i H(06.LcoailsskiO6 mloae high-fat ameliorates 36 lipopolysaccharide research OK67 microbiota Nutrition sakei gut Lactobacillus expression. inhibiting protein (2016). by junction DH tight mice colon Kim in inducing obesity & gut 102 and and MJ, alters America production intolerance Han Obesity of glucose KH, States blood Woo (2005). United diet-induced JJ, JI the of Jeong of Gordon levels SM, Sciences improved & Lim of carbohydrate RD, Academy high Knight National to CA, the fat of Lozupone 11070-11075. 57 high P, Proceedings journal from Turnbaugh Endocrine ecology. diet F, diet. microbial in high-fat Backhed Shifts a RE, fed Ley mice (2010). in R cytokines Choue pro-inflammatory & and G, adipokines Shin IS, treatment Lee probiotics 15 IS by one pathway Choi PGC-1alpha PloS BK, the mice. Kim of in activation H, through Joung dysfunctions C, 6 metabolic Lee communications diet-induced B, Nature AF Kim resistance. J, Bassas insulin Kwon SH, mediates Kwak nutritional gene KC, of adiponectin Shin Journal the inhibits X, of SBT2055 Pan diet. thylation YJ, gasseri high-fat Park Lactobacillus a AY, fed Kim (2016). mice Y in Kadooka permeability & intestinal 5 F, science and Sakai inflammation 498 A, Nature tissue Ogawa control. adipose M, glucose Miyoshi diabetic M, and Kawano the impaired B of normal, Fagerberg CJ, microbiota with Behre 20 women The G, Obesity European Bergstrom (2012). in weight. I, K Nookaew body Thorngren-Jerneck V, Tremaroli excessive & FH, and S, Karlsson normal Ahrne with G, In- children Molin preschool and High-Fat- J, in Expression Alleviates Xu gut SIRT1 sakei J, 63 Lactobacillus and research Onnerfalt Activation food CL, (2019). & AMPK Karlsson DH nutrition Inducing Molecular Kim by & Activation. NF-kappaB HB, Mice Microbiota-Mediated Endothelial Jang in Gut and SJ, hibiting Anxiety Oh Hypertension and JK, Induces Obesity Kim Leptin 67 Diet-Induced SK, Hypertension (2016). Han Mice. HM, EJ Female Jang Chantemele Obese de in Belin Mechanisms Aldosterone-Dependent & via Jr., Gastroenterology Dysfunction L, obesity. Otvos of AC, independently Huby microbiome gut murine the YY of gut Chen 137 composition M, 109 human Hamady the America SA, the determines Keilbaugh of SA, of diet States Sherrill-Mix Proceedings United C, biology the Hoffmann disease. systems MA, of bowel Hildebrandt Sciences inflammatory Metagenomic of and Academy obesity (2012). National with the E associated of shifts Borenstein topological & reveals intestinal PJ, microbiome on Turnbaugh flavonoids of S, Effects and research Greenblum Nutrition (2016). microbiota obesity. X diet-induced Terra Gut during & microbiota M, 29 gut (2014). Blay reviews in changes A, A and Ardevol integrity Colecchia M, barrier & Pinent inflammation, I, M, the Gines Taddia K, is 20 G, Gil-Cardoso gastroenterology who of Marasco and journal chicken LH, World the Eusebi syndrome. is R, metabolic who Schiumerini 105 D, disorders: nutrition Festi clinical metabolic of and journal obesity, American permeability, The Gut egg? 110 America (2017). of A States LB Fasano United Bindels National the the C, of of Druart Sciences Proceedings JP, of obesity. diet-induced Ouwerkerk Academy controls obesity, epithelium 105 L, between intestinal practice Geurts and link muciniphila clinical a Akkermansia C, and as Belzer research Inflammation A, Diabetes (2014). Everard N diabetes. Paquot 2 & type AJ, and Scheen syndrome J, Piette metabolic S, Legrand-Poels N, Esser : 7612 e1711-1712. 1716-1724 : : e23. 234-248. : e0228932. : tal. et , 12 3-4. : : tal. et , 9066-9071. 22) opeesv mloaino high-fat of amelioration Comprehensive (2020). 16079-16094. 21) bst-nue N hyperme- DNA Obesity-induced (2015). tal. et , : 594-599. tal. et , : 2257-2261. 21) rs-akbetween Cross-talk (2013). 21) u metagenome Gut (2013). tal. et , : : 99-103. 141-150. : : 337-348. 7585. 20) High-fat (2009). : : 39-50. 1020-1028. : e1800978. : Posted on Authorea 23 Jul 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159551303.38968103 — This a preprint and has not been peer reviewed. Data may be preliminary. emnu ET76 oe lentv o h rvnino aclrdsresi os oe of model mouse Societies a American of in Federation disorders the vascular of publication of 33 F official Biology prevention O’Valle : Experimental M, the journal for Sanchez FASEB for N, erythematosus. alternative Visitacion lupus novel la systemic a de M, CECT5716: Romero fermentum I, Robles-Vera M, Toral obese in 127 status pro-inflammatory Science and Clinical pro-oxidant vascular mice. the MP reduces ZDF Utrilla CECT5711 S´anchez coryniformis using M, Lactobacillus M, analysis vivo Romero G´omez-Guzm´an in Jim´enez R, M, an M, L Toral syndrome: 98 Rodes biotechnology metabolic A, and of markers microbiology on Labbe on Applied ML, Probiotics 5221 rats. Jones NCIMB of fermentum M, Effects L. 12. Malhotra administered (2020). Nutrients S, Trials. C Saha Clinical C, Gomez-Llorente Randomized Tomaro-Duchesneau of Clinical & Review factors. A, Systematic A risk Gil Syndrome: syndrome MJ, Metabolic Martinez-Ramirez metabolic C, with CL Tenorio-Jimenez Ferreira correlated J, are Bressan patients SC, 31 obese Franceschini nutrition in PG, parameters Chiarello NC, 341 permeability medicine Souza resistance of TF, insulin journal for Teixeira England The action–implications New insulin Pharmacotherapy. The and Obesity transporters mellitus. Glucose (2018). diabetes (1999). LJ and BB Kahn Aronne & & PR, Shepherd RB, 102 America Kumar North LI, 20 of Igel reports clinics hypertension D, Medical Current Umashanker Syndrome. KH, Metabolic Saunders the of Epidemic Nutrients Global Acids. 12. The Fatty (2018). and MG 4 Saklayen Receptor Toll-Like Inflammation, Obesity, (2018). PC 10. Calder & MM, properties. Rogero anti-inflammatory intestinal exert 6 to Function essential not & M is Food Comalada CECT5716 M, fermentum Olivares Lactobacillus N, of research Garrido-Mesa bility food T, Vezza & F, nutrition Algieri Rodr´ıguez-Nogales Molecular mouse A, DSS composition. microbiota in and salivarius expression Lactobacillus 61. microRNAs and N on fermentum Chueca impact MP, Lactobacillus Utrilla colitis: of T, effects Vezza 62 research J, anti-inflammatory Garrido-Mesa intestinal food Hypertension F, & with Algieri nutrition Rats A, M Molecular Olivares in Rodriguez-Nogales Blockade. Stress M, Oxide Oxidative Romero Nitric Vascular M, Chronic and Sanchez by Dysbiosis N, Induced Prevents microbiota. Visitacion fermentum the la Lactobacillus in de changes otic M, with Toral fatty associated diet I, of Robles-Vera fructose development 61. high research the a prevents food M fed FOS & rats Olivares nutrition in and AM, Molecular alterations CECT5716 Aransay glycemic fermentum and JL, Lactobacillus liver Lavin acid of MD, 143 composed Suarez pediatrics synbiotic of R, A J Journal Gamez-Belmonte Xaus The B, ML, gut. Rivero-Gutierrez Marin infant E, the Jiminez for bacteria C, acid Reviriego lactic S, 65 Langa Gut G R, frontier. Hold Martin clinical GM, new Hirschfield a GD, Hermes health: host F, Fava Nutrition and DH, microbiota. Adams in gut JR, colitis by Marchesi diet-induced production high-fat lipopolysaccharide ameliorates and IM38 41 activation adolescentis research NF-kappaB Bifidobacterium inhibiting (2017). by DH mice Kim & SM, Lim : : 735-740. 86-96. : 1176-1184. : 33-45. : 10005-10018. : 135-148. : : 330-339. 115-126. 13 tal. et , : 248-257. : 754-758. tal. et , 20) ua iki oreof source a is milk Human (2003). tal. et , tal. et , tal. et , 21) h u microbiota gut The (2016). tal. et , tal. et , tal. et , : e1800298. tal. et , 21) ffc forally of Effect (2014). 21) h probiotic The (2014). 21) Lactobacillus (2019). 21) h Probi- The (2018). 21) Differential (2017). 21) Intestinal (2012). 21) h via- The (2015). tal. et , (2017). : Posted on Authorea 23 Jul 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159551303.38968103 — This a preprint and has not been peer reviewed. Data may be preliminary. n- os W GATTTTG- FW: TAGTCCTTCC- FW: Mouse GAGAATACAGC- FW: Mouse GACTTC- FW: Jnk-1 Mouse GATGGCAGA- T FW: Annealing Il-6 CCATCAC- FW: Mouse Il-1 3’ 5’- Sequence Glut4 Mouse Mouse Ampk Organism Adiponectin Gapdh fermentum Lactobacillus Gene of Effects Anti-Obesity (2019). X Signaling 1. PPAR-alpha Zhao Table through & Mice X, Obese Diet-Induced Zhou 7. High-Fat R, Microorganisms in Pathway. Pickle Yi Sichuan J, from Isolated Mu CQPC05 F, Tan K, Zhu 58 M receptor- Romero proliferator-activated A, peroxisome 10 Nieto S´anchezof immunology M, P, Mucosal Galindo Jim´enez R, mice. S MJ, Fukuda in Zarzuelo S, sensitivity Ryu insulin SH, improves Lee and rRNA Y, obesity of 73 Kim assignment prevents microbiology rapid YS, environmental for Lee and classifier JY, Bayesian Applied Yang . Naive (2007). bacterial JR new Cole the & into JM, sequences Tiedje GM, Garrity G Q, 35 Naughton Wang biology cross-sectional B, vascular dysfunction: vascular Lesourd and generalized present thrombosis, R, mellitus Arteriosclerosis, diabetes Chapier in study. 2 properties. type F, obesity immunomodulatory without and Dutheil its diet-induced with P, individuals to in and Obert extract dysbiosis G, leaf microbiota Walther L.) gut europaea of amelioration 150 (Olea M research the olive Sanchez Pharmacological to of M, related Romero effects are J, protective mice Garrido-Mesa vascular F, (GLUT4). and Algieri 4 tabolic A, Type Transporter Rodriguez-Nogales Glucose T, Physiology, Vezza (2020). (FL). MA Island Sepulveda Treasure Carrillo StatPearls. & In V, Podder E, Vargas : β 733-743. rmrsqecsue nR-PRassays RT-qPCR in used sequences Primer os W TGATGAGAAT- FW: Mouse : 104487. β ciaini pnaeul yetniert.Hypertension rats. hypertensive spontaneously in activation tal. et , 14 TAGCCCATGCCGAGAATGA RV: GACTGGCGAGGACT TTGGTCCTTAGCCACTCCTTCC RV: TACCCCAATTTCC CTTCTTCAAAGATGAAGGAAA RV: GACCTCTTCT TCTTATTGCAGCAGCGCCTGAG RV: TAGGACCAGTG CGCGCGACTATCAAAGACATACG RV: CTTCACAGCCTCATC CTTGCCAGTGCTGCCGTCAT RV: GATGGCACTCC CCTGCTTCACCACCTTCTTG RV: CATCTTCCAGGAG : 21) u omna atrie acidifaciens Bacteroides commensal Gut (2017). 1022-1029. tal. et , tal. et , 21) niyetnieeffects Antihypertensive (2011). 21) eaoi syndrome Metabolic (2015). : tal. et , 104-116. 60 60 60 62 60 52 60 : 5261-5267. 21) h me- The (2019). ° C Posted on Authorea 23 Jul 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159551303.38968103 — This a preprint and has not been peer reviewed. Data may be preliminary. o1MueF:GGGGCCTA- FW: fat); FW: and epididymal (AUC) and curve abdominal the efficiency, under Mouse area energy intake, energy evolution, 1. Figure CCTG- FW: LEGENDS FIGURE Mouse Zo-1 Mouse ACGGACCCT- FW: Tnf- CGTGGTCAACT- FW: Tlr4 GCAGTC- FW: Mouse Tff3 GCAGTC- FW: Mouse Ppar- AGCCAACTCT- FW: Mouse Occludin FW: Mouse Muc-3 T Annealing TTCACA- Mouse FW: Muc-2 3’ 5’- Sequence Mouse Muc-1 Mouse Mcp-1 Organism R Leptin Leptin Gene α α ffcsof Effects .fermentum L. os W AACTAGTGGT- FW: Mouse AGGCTG- FW: Mouse c) pddmlaioetsu,aaye yhmtxlnadesnstaining eosin and hematoxylin by analysed tissue, adipose Epididymal ET76amnsrto on administration CECT5716 15 TGGAGATGAGGCTTCTGCTT RV: CACTGATCAAGA CTTCACAGAGCAATGACTCC RV: GCCAGCCGAT AGATCAACCGATGGACGTGTAA RV: TAAGCTCC GCCTTTCAGGGAAT- GCCACGGTTGTTACACTGCTC RV: CTCTG GTTGCTGGGTC- GGCATTTGTTCCGGTTCTTC RV: TAAGGGCTTCTTTCG TCAGCAGCAGCCATGTACTC RV:GACCACTATGA CGGCTCTATCTCTACGCTCTCC RV: GCGAGAATGG CACCGTGGGGCTACTGGAGAG RV: CTCAGTGGCACCTC CACCGTGGGCTACTGGAGAG RV: CTCAGTGGCACCTC TCTCCAGCCTACTCATTG RV: CACTGAAG TGCCTGGGCCTCTATCTC RV: GATGT GCTATTTTGGGAA- GCTGGTGAGGACCTGTTGAT RV: CACGCAGTCGGTAT a) opooia hne bd weight (body changes morphological b) lcs oeac etand test tolerance Glucose 56 60 60 60 62 56 60 60 60 55 60 60 ° C Posted on Authorea 23 Jul 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159551303.38968103 — This a preprint and has not been peer reviewed. Data may be preliminary. of-gut-microbiota-dysbiosis fermentum-cect5716-ameliorates-high-fat-diet-induced-obesity-in-mice-through-modulation- 1.pdf Figure ( mice obese file treatment Hosted the in and differences HFD-group drove and mice, and HFD-group control abundant mice), differentially (control were b) that mice States) non-obese Unobserved in of Reconstruction by munities a) 8. Spearman. Figure of test non-parametric using Correlation markers. S1. (P Figure differ statistically letter different with Groups index); c) Shannon and OTUs Observed tree, 7. Figure VAS2870; Tnf- inhibitor means oxidase Tlr4, as NADPH of expressed presence expression the gene or and absence activity the in relaxation dependent 6. Figure means as qPCR; expressed time real by analysed markers integrity 5. 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SEM a) nhg a it(F)fdmc,analysed mice, (HFD)-fed diet fat high in Tff-3 a) irboedvriy(ho,P whole PD (Chao1, diversity microbiome Tlr4 b) eeepeso fitsia barrier intestinal of expression gene D/D ai n Triglycerides and ratio LDL/HDL nhg a it(F)fdmice, (HFD)-fed diet fat high in nhg a it(F)fdmice, (HFD)-fed diet fat high in ± E n1) ruswith Groups (n=10). SEM c) orlto ewrsfor networks Correlation .fermentum L. < < 0.05). 0.05). b) ± a) otcNADPH aortic E (n=10). SEM endothelium- ± group); Leptin a) SEM. Il-6 Posted on Authorea 23 Jul 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159551303.38968103 — This a preprint and has not been peer reviewed. Data may be preliminary. Figure 2

mg/dL a) b) Control Control Control Control a a diet diet LDL/HDL Glucose HFD HFD b b L. L. fermentum fermentum a c

mg/dL pmol/L Control Control Control Control a diet diet Triglycerides 17 Insulin HFD HFD b L. L. fermentum fermentum c Control Control a diet HOMA HFD b - IR L. fermentum a Posted on Authorea 23 Jul 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159551303.38968103 — This a preprint and has not been peer reviewed. Data may be preliminary.

Fold increase Fold increase Fold increase Fold increase Figure 3 b) a) Control Control Control Control Control Control Control Control a a a Mcp a diet diet diet Ppar diet Il Tlr4 - HFD HFD - 6 HFD b 1 HFD b b ⍺ b ( ( liver ( liver ( liver L. L. L. fat L. fermentum fermentum fermentum fermentum a ) a a ) a ) ) Control Control Control Control Control Control Control Control a a a a diet diet diet Glut4 Mcp diet Tlr4 Il - HFD HFD HFD 6 b b HFD b - b 1 ( ( ( fat fat fat ( L. L. L. fat L. fermentum fermentum fermentum ) fermentum ) ) a c c ) a 18 Control Control Control Control Control Control a a a Ampk Tnf diet diet Jnk diet - HFD HFD HFD - ⍺ b b b 1 ( ( liver ( liver liver L. L. L. fermentum fermentum fermentum a a ) a ) ) Control Control Control Control Control Control a a a diet diet diet Ampk Tnf Jnk HFD HFD HFD - - b b b ⍺ 1 ( ( ( fat fat L. L. L. fat fermentum fermentum fermentum ) ) a ) a a Posted on Authorea 23 Jul 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159551303.38968103 — This a preprint and has not been peer reviewed. Data may be preliminary. Figure 4

Fold increase Fold increase Control Control diet diet a a Leptin Leptin HFD HFD b b - R ( fat ( fat L. L. L. L. fermentum ) fermentum ) a a 19 Control Control diet diet a a Adiponectin Leptin HFD HFD b b - R ( L. L. L. L. liver ( fermentum fermentum fat a c ) ) Posted on Authorea 23 Jul 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159551303.38968103 — This a preprint and has not been peer reviewed. Data may be preliminary. Figure

b) Fold increase Fold increase a) Control 5 Control diet diet a a Muc Zo - - 1 1 HFD HFD (colon) (colon) b b L. L. L. L. fermentum EU/ml fermentum a a

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Erysipelotrichaceae Posted on Authorea 23 Jul 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159551303.38968103 — This a preprint and has not been peer reviewed. Data may be preliminary. Figure S1 23 Posted on Authorea 23 Jul 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159551303.38968103 — This a preprint and has not been peer reviewed. Data may be preliminary. Figure 8 c) a) HFD Control L. fermentum diet b) 24