Anti-obesity effect of Lactobacillus rhamnosus LS-8 and Lactobacillus crustorum MN047 on high-fat and high-fructose diet mice base on inflammatory response alleviation and gut microbiota regulation
The objective of the study was to evaluate the anti-obesity effect of Lactobacillus rhamnosus LS-8 and Lactobacillus crustorum MN047, and illustrate the potential functional mechanism about the alleviation of high fat and high fructose diet (HFFD) induced obesity and related metabolic abnormalities.
C57BL/6J mice were subjected to a standard or HFFD with or without supplementation of L. rhamnosus LS-8 and L. crustorum MN047 for 10 weeks. Obesity related metabolic indices including glucose tolerance, insulin resistance, serum lipid, liver function, hormones and inflammatory cytokines were assessed by standard protocols. For the monitoring of inflammatory response and lipid metabolism, transcriptional levels were profiled in liver and/or adipose tissues. Furthermore, gut microbiota composition analyses in the fecal samples were performed using 16S rRNA gene sequencing, and gut microbial metabolites, including lipopolysaccharide (LPS) and short-chain fatty acids (SCFAs), were also tested for the assessment of the relationship between gut microbiota variation and inflammatory response.
Administration with L. rhamnosus LS-8 and L. crustorum MN047 significantly mitigated body weight gain and insulin resistance, and inflammatory response (TNF-α, IL-1β and IL-6 levels in serum and corresponding mRNA levels in adipose tissues) was significantly inhibited in these two strains-treated mice. Moreover, L. rhamnosus LS-8 and L. crustorum MN047 could partially normalized mRNA expression levels involved in lipid metabolism including Pparγ, Srebp-1c, CD36, Fabp2 and FAS. In addition, these two strains manipulated gut microbiota by decreasing the abundance of Bacteroides and Desulfovibrio and increasing that of Lactobacillus and Bifidobacterium, which in turn raised the levels of feces SCFAs and lowered the levels of circulating LPS.
These results indicated that L. rhamnosus LS-8 and L. crustorum MN047 supplementation possessed the anti-obesity effect on the HFFD fed mice by alleviating inflammatory response and regulating gut microbiota, which further suggested that these two probiotics can be considered as an alternative dietary supplement in combination with the preventive and therapeutic strategies against obesity and related complications.
KeywordsDiet-induced obesity Lipid metabolism Inflammation Lactobacillus rhamnosus LS-8 Lactobacillus crustorum MN047 Gut microbiota
This work was financially supported by Special Fund for Agro-scientific Research in the Public Interest [Grant No. 201503135].
TW and XL designed the study and wrote the manuscript; HY and YL performed the experiments; XL and XW analyzed the data; YS and YY interpreted the results of experiments; BL and YZ prepared figures. All authors read and approved the final manuscript.
Compliance with ethical standards
Conflict of interest
The authors have declared no conflicts of interest.
All animal experiments were carried out in accordance with the Guide for the Care and Use of Laboratory Animals: Eighth Edition, ISBN-10: 0-309-15396-4, and experimental procedures were approved by the Animal Ethics Committee of Xi’an Jiaotong University.
- 6.Xu HY, Barnes GT, Yang Q, Tan Q, Yang DS, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Investig 112(12):1821–1830. https://doi.org/10.1172/jci200319451 CrossRefPubMedGoogle Scholar
- 10.Roselli M, Finamore A, Brasili E, Rami R, Nobili F, Orsi C, Zambrini AV, Mengheri E (2018) Beneficial effects of a selected probiotic mixture administered to high fat-fed mice before and after the development of obesity. J Funct Foods 45:321–329. https://doi.org/10.1016/j.jff.2018.03.039 CrossRefGoogle Scholar
- 11.Hsieh FC, Lan CC, Huang TY, Chen KW, Chai CY, Chen WT, Fang AH, Chen YH, Wu CS (2016) Heat-killed and live Lactobacillus reuteri GMNL-263 exhibit similar effects on improving metabolic functions in high-fat diet-induced obese rats. Food Funct 7(5):2374–2388. https://doi.org/10.1039/c5fo01396h CrossRefPubMedGoogle Scholar
- 12.Kamei N, Tobe K, Suzuki R, Ohsugi M, Watanabe T, Kubota N, Ohtsuka-Kowatari N, Kumagai K, Sakamoto K, Kobayashi M, Yamauchi T, Ueki K, Oishi Y, Nishimura S, Manabe I, Hashimoto H, Ohnishi Y, Ogata H, Tokuyama K, Tsunoda M, Ide T, Murakami K, Nagai R, Kadowaki T (2006) Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance. J Biol Chem 281(36):26602–26614. https://doi.org/10.1074/jbc.M601284200 CrossRefPubMedGoogle Scholar
- 14.David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, Ling AV, Devlin AS, Varma Y, Fischbach MA, Biddinger SB, Dutton RJ, Turnbaugh PJ (2014) Diet rapidly and reproducibly alters the human gut microbiome. Nature 505(7484):559. https://doi.org/10.1038/nature12820 CrossRefPubMedGoogle Scholar
- 15.Martinez-Guryn K, Hubert N, Frazier K, Urlass S, Musch MW, Ojeda P, Pierre JF, Miyoshi J, Sontag TJ, Cham CM, Reardon CA, Leone V, Chang EB (2018) Small intestine microbiota regulate host digestive and absorptive adaptive responses to dietary lipids. Cell Host Microbe 23(4):458. https://doi.org/10.1016/j.chom.2018.03.011 CrossRefPubMedPubMedCentralGoogle Scholar
- 17.Engevik MA, Versalovic J (2017) Biochemical features of beneficial microbes: foundations for therapeutic microbiology. Microbiol Spectr 5(5):35. https://doi.org/10.1128/microbiolspec.BAD-0012-2016 CrossRefGoogle Scholar
- 18.Delzenne NM, Cani PD (2011) Interaction between obesity and the gut microbiota: relevance in nutrition. In: Cousins RJ, Bier DM, Bowman BA (eds) Annual review of nutrition, vol 31. Annual Reviews, Palo Alto, pp 15–31. https://doi.org/10.1146/annurev-nutr-072610-145146 CrossRefGoogle Scholar
- 19.Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C, Waget A, Delmee E, Cousin B, Sulpice T, Chamontin B, Ferrieres J, Tanti JF, Gibson GR, Casteilla L, Delzenne NM, Alessi MC, Burcelin R (2007) Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56(7):1761–1772. https://doi.org/10.2337/db06-1491 CrossRefGoogle Scholar
- 20.Mei XR, Zhang XY, Wang ZG, Gao ZY, Liu G, Hu HL, Zou L, Li XL (2016) Insulin sensitivity-enhancing activity of phlorizin is associated with lipopolysaccharide decrease and gut microbiota changes in obese and type 2 diabetes (db/db) mice. J Agric Food Chem 64(40):7502–7511. https://doi.org/10.1021/acs.jafc.6b03474 CrossRefPubMedGoogle Scholar
- 21.Kadooka Y, Sato M, Imaizumi K, Ogawa A, Ikuyama K, Akai Y, Okano M, Kagoshima M, Tsuchida T (2010) Regulation of abdominal adiposity by probiotics (Lactobacillus gasseri SBT2055) in adults with obese tendencies in a randomized controlled trial. Eur J Clin Nutr 64(6):636–643. https://doi.org/10.1038/ejcn.2010.19 CrossRefPubMedGoogle Scholar
- 22.Park DY, Ahn YT, Park SH, Huh CS, Yoo SR, Yu R, Sung MK, McGregor RA, Choi MS (2013) Supplementation of Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 in diet-induced obese mice is associated with gut microbial changes and reduction in obesity. PLoS One. https://doi.org/10.1371/journal.pone.0059470 CrossRefPubMedPubMedCentralGoogle Scholar
- 26.Balakumar M, Prabhu D, Sathishkumar C, Prabu P, Rokana N, Kumar R, Raghavan S, Soundarajan A, Grover S, Batish VK, Mohan V, Balasubramanyam M (2018) Improvement in glucose tolerance and insulin sensitivity by probiotic strains of Indian gut origin in high-fat diet-fed C57BL/6J mice. Eur J Nutr 57(1):279–295. https://doi.org/10.1007/s00394-016-1317-7 CrossRefPubMedGoogle Scholar
- 27.Haffner SM, Greenberg AS, Weston WM, Chen HZ, Williams K, Freed MI (2002) Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease in patients with type 2 diabetes mellitus. Circulation 106(6):679–684. https://doi.org/10.1161/01.cir.0000025403.20953.23 CrossRefPubMedGoogle Scholar
- 31.Schloss PD, Westcott SL, Ryabin T, Hall JR, Hartmann M, Hollister EB, Lesniewski RA, Oakley BB, Parks DH, Robinson CJ, Sahl JW, Stres B, Thallinger GG, Van Horn DJ, Weber CF (2009) Introducing mothur: open-Source, platform-independent, community-supported software for describing and comparing microbial communities. Appl Environ Microbiol 75(23):7537–7541. https://doi.org/10.1128/aem.01541-09 CrossRefPubMedPubMedCentralGoogle Scholar
- 33.Liu ZG, Qiao QL, Sun YL, Chen YW, Ren B, Liu XB (2017) Sesamol ameliorates diet-induced obesity in C57BL/6J mice and suppresses adipogenesis in 3T3-L1 cells via regulating mitochondria-lipid metabolism. Mol Nutr Food Res. https://doi.org/10.1002/mnfr.201600717 CrossRefPubMedPubMedCentralGoogle Scholar
- 34.Lee E, Jung SR, Lee SY, Lee NK, Paik HD, Lim SI (2018) Lactobacillus plantarum strain Ln4 attenuates diet-induced obesity, insulin resistance, and changes in hepatic mrna levels associated with glucose and lipid metabolism. Nutrients 10(5):643. https://doi.org/10.3390/nu10050643 CrossRefPubMedCentralGoogle Scholar
- 35.Pothuraju R, Sharma RK, Kumar KP, Chagalamarri J, Jangra S, Bhakri G, De S (2016) Anti-obesity effect of milk fermented by Lactobacillus plantarum NCDC 625 alone and in combination with herbs on high fat diet fed C57BL/6J mice. Benef Microbes 7(3):1. https://doi.org/10.3920/BM2015.0083 CrossRefGoogle Scholar
- 39.Grunfeld C, Zhao C, Fuller J, Pollock A, Moser A, Friedman J, Feingold KR (1996) Endotoxin and cytokines induce expression of leptin, the ob gene product, in hamsters—a role for leptin in the anorexia of infection. J Clin Investig 97(9):2152–2157. https://doi.org/10.1172/jci118653 CrossRefPubMedGoogle Scholar
- 42.Cranford TL, Enos RT, Velazquez KT, McClellan JL, Davis JM, Singh UP, Nagarkatti M, Nagarkatti PS, Robinson CM, Murphy EA (2016) Role of MCP-1 on inflammatory processes and metabolic dysfunction following high-fat feedings in the FVB/N strain. Int J Obes 40(5):844–851. https://doi.org/10.1038/ijo.2015.244 CrossRefGoogle Scholar
- 44.Zhu J, Tang HY, Zhang ZH, Zhang Y, Qiu CF, Zhang L, Huang PE, Li F (2017) Kaempferol slows intervertebral disc degeneration by modifying LPS-induced osteogenesis/adipogenesis imbalance and inflammation response in BMSCs. Int Immunopharmacol 43:236–242. https://doi.org/10.1016/j.intimp.2016.12.020 CrossRefPubMedGoogle Scholar
- 46.Moya-Pérez A, Neef A, Sanz Y (2015) Bifidobacterium pseudocatenulatum CECT 7765 reduces obesity-associated inflammation by restoring the lymphocyte-macrophage balance and gut microbiota structure in high-fat diet-fed mice. PLoS One. https://doi.org/10.1371/journal.pone.0126976 CrossRefPubMedPubMedCentralGoogle Scholar
- 48.Singh DP, Khare P, Bijalwan V, Baboota RK, Singh J, Kondepudi KK, Chopra K, Bishnoi M (2017) Coadministration of isomalto-oligosaccharides augments metabolic health benefits of cinnamaldehyde in high fat diet fed mice. BioFactors 43(6):821–835. https://doi.org/10.1002/biof.1381 CrossRefPubMedGoogle Scholar
- 49.Kang C, Wang B, Kaliannan K, Wang XL, Lang HD, Hui SC, Huang L, Zhang Y, Zhou M, Chen MT, Mi MT (2017) Gut microbiota mediates the protective effects of dietary capsaicin against chronic low-grade inflammation and associated obesity induced by high-fat diet. mBio 8(3):14. https://doi.org/10.1128/mBio.00470-17 CrossRefGoogle Scholar
- 50.Moreno-Navarrete JM, Ortega F, Serino M, Luche E, Waget A, Pardo G, Salvador J, Ricart W, Fruhbeck G, Burcelin R, Fernandez-Real JM (2012) Circulating lipopolysaccharide-binding protein (LBP) as a marker of obesity-related insulin resistance. Int J Obes 36(11):1442–1449. https://doi.org/10.1038/ijo.2011.256 CrossRefGoogle Scholar
- 53.Thiennimitr P, Yasom S, Tunapong W, Chunchai T, Wanchai K, Pongchaidecha A, Lungkaphin A, Sirilun S, Chaiyasut C, Chattipakorn N (2018) Lactobacillus paracasei HII01, xylooligosaccharides and synbiotics reduced gut disturbance in obese rats. Nutrition 54:40–47. https://doi.org/10.1016/j.nut.2018.03.005 CrossRefPubMedGoogle Scholar
- 57.Liang Y, Lin C, Zhang Y, Deng Y, Liu C, Yang Q (2018) Probiotic mixture of Lactobacillus and Bifidobacterium alleviates systemic adiposity and inflammation in non-alcoholic fatty liver disease rats through Gpr109a and the commensal metabolite butyrate. Inflammopharmacology 26(4):1051–1055CrossRefGoogle Scholar