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Modified apple polysaccharide regulates microbial dysbiosis to suppress high-fat diet-induced obesity in C57BL/6J mice

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European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Purpose

Obesity, substantially increasing the risk of diseases such as metabolic diseases, becomes a major health challenge. In this study, we, therefore, investigated the effect of modified apple polysaccharide (MAP) on obesity.

Methods

Twelve male C57BL/6J mice were given a 45% high-fat diet (HFD) for 12 weeks to replicate an obesity model and six mice were given normal diet as control. Then, 1 g/kg MAP was administrated to six mice by gavage for 15 days. Illumina Miseq PE300 sequencing platform was used to analyze the microbial diversity of fecal samples. Flow cytometry was employed to investigate the effects of MAP on immune cells in adipose tissue. Bacterial culture and qPCR were used to assess the effects of MAP on the growth of whole fecal bacteria and representative microbiota in vitro.

Results

MAP could alleviate HFD-induced obesity and decrease body weight of mice effectively. The results of α diversity showed that Shannon index in HFD group was significantly lower than that in control group; Shannon index in MAP group was higher than that in HFD group. The results of β diversity showed that the microbiota of MAP group was more similar to that of control group. HFD increased the number of T cells and macrophages in adipocytes; while MAP decreased the number of T cells and macrophages. MAP could promote the growth of fecal bacteria, and demonstrated a facilitated effect on the proliferation of Bacteroidetes, Bacteroides, Lactobacillus, and an inhibitory effect on Fusobacterium.

Conclusions

MAP could reduce HFD-induced obesity of mice effectively. The possible mechanisms are that MAP restored HFD-induced intestinal microbiota disorder, downregulated the number of T cells and macrophages in adipose tissue.

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Abbreviations

BDE:

Bacteroides

BTE:

Bacteroidetes

FIR:

Firmicutes

FUS:

Fusobacterium

HDL-C:

High-density lipoprotein cholesterol

HFD:

High-fat diet

LDL-C:

Low-density lipoprotein cholesterol

LAC:

Lactobacillus

MAP:

Colitis-associated colorectal cancer

TC:

Total cholesterol

TG:

Triglyceride

References

  1. Prospective Studies C, Whitlock G, Lewington S, Sherliker P, Clarke R, Emberson J, Halsey J, Qizilbash N, Collins R, Peto R (2009) Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet 373(9669):1083–1096. https://doi.org/10.1016/S0140-6736(09)60318-4

    Article  Google Scholar 

  2. Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, Mullany EC, Biryukov S, Abbafati C, Abera SF, Abraham JP, Abu-Rmeileh NM, Achoki T, AlBuhairan FS, Alemu ZA, Alfonso R, Ali MK, Ali R, Guzman NA, Ammar W, Anwari P, Banerjee A, Barquera S, Basu S, Bennett DA, Bhutta Z, Blore J, Cabral N, Nonato IC, Chang JC, Chowdhury R, Courville KJ, Criqui MH, Cundiff DK, Dabhadkar KC, Dandona L, Davis A, Dayama A, Dharmaratne SD, Ding EL, Durrani AM, Esteghamati A, Farzadfar F, Fay DF, Feigin VL, Flaxman A, Forouzanfar MH, Goto A, Green MA, Gupta R, Hafezi-Nejad N, Hankey GJ, Harewood HC, Havmoeller R, Hay S, Hernandez L, Husseini A, Idrisov BT, Ikeda N, Islami F, Jahangir E, Jassal SK, Jee SH, Jeffreys M, Jonas JB, Kabagambe EK, Khalifa SE, Kengne AP, Khader YS, Khang YH, Kim D, Kimokoti RW, Kinge JM, Kokubo Y, Kosen S, Kwan G, Lai T, Leinsalu M, Li Y, Liang X, Liu S, Logroscino G, Lotufo PA, Lu Y, Ma J, Mainoo NK, Mensah GA, Merriman TR, Mokdad AH, Moschandreas J, Naghavi M, Naheed A, Nand D, Narayan KM, Nelson EL, Neuhouser ML, Nisar MI, Ohkubo T, Oti SO, Pedroza A, Prabhakaran D, Roy N, Sampson U, Seo H, Sepanlou SG, Shibuya K, Shiri R, Shiue I, Singh GM, Singh JA, Skirbekk V, Stapelberg NJ, Sturua L, Sykes BL, Tobias M, Tran BX, Trasande L, Toyoshima H, van de Vijver S, Vasankari TJ, Veerman JL, Velasquez-Melendez G, Vlassov VV, Vollset SE, Vos T, Wang C, Wang X, Weiderpass E, Werdecker A, Wright JL, Yang YC, Yatsuya H, Yoon J, Yoon SJ, Zhao Y, Zhou M, Zhu S, Lopez AD, Murray CJ, Gakidou E (2014) Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 384(9945):766–781. https://doi.org/10.1016/S0140-6736(14)60460-8

    Article  PubMed  PubMed Central  Google Scholar 

  3. Collaboration NCDRF (2016) Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants. Lancet 387(10026):1377–1396. https://doi.org/10.1016/s0140-6736(16)30054-x

    Article  Google Scholar 

  4. Kinlen D, Cody D, O’Shea D (2018) Complications of obesity. QJM 111(7):437–443. https://doi.org/10.1093/qjmed/hcx152

    Article  CAS  PubMed  Google Scholar 

  5. Apovian CM (2016) Obesity: definition, comorbidities, causes, and burden. Am J Manag Care 22(7 Suppl):s176–s185

    PubMed  Google Scholar 

  6. Noncommunicable Diseases Progress Monitor, 2017 (2017) World Health Organization (WHO), p 231. https://www.who.int/nmh/publications/ncd-progress-monitor-2017/en/(2017)

  7. Bäckhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, Semenkovich CF, Gordon JI (2004) The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci USA 101(44):15718–15723. https://doi.org/10.1073/pnas.0407076101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ridaura VK, Faith JJ, Rey FE, Cheng J, Duncan AE, Kau AL, Griffin NW, Lombard V, Henrissat B, Bain JR, Muehlbauer MJ, Ilkayeva O, Semenkovich CF, Funai K, Hayashi DK, Lyle BJ, Martini MC, Ursell LK, Clemente JC, Van Treuren W, Walters WA, Knight R, Newgard CB, Heath AC, Gordon JI (2013) Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 341(6150):1241214. https://doi.org/10.1126/science.1241214

    Article  CAS  PubMed  Google Scholar 

  9. Lazar V, Ditu LM, Pircalabioru GG, Picu A, Petcu L, Cucu N, Chifiriuc MC (2019) Gut microbiota, host organism, and diet trialogue in diabetes and obesity. Front Nutr 6:21. https://doi.org/10.3389/fnut.2019.00021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Wang S, Li Q, Zang Y, Zhao Y, Liu N, Wang Y, Xu X, Liu L, Mei Q (2017) Apple polysaccharide inhibits microbial dysbiosis and chronic inflammation and modulates gut permeability in HFD-fed rats. Int J Biol Macromol 99:282–292. https://doi.org/10.1016/j.ijbiomac.2017.02.074

    Article  CAS  PubMed  Google Scholar 

  11. Zhang D, Li YH, Mi M, Jiang FL, Yue ZG, Sun Y, Fan L, Meng J, Zhang X, Liu L, Mei QB (2013) Modified apple polysaccharides suppress the migration and invasion of colorectal cancer cells induced by lipopolysaccharide. Nutr Res 33(10):839–848. https://doi.org/10.1016/j.nutres.2013.06.004

    Article  CAS  PubMed  Google Scholar 

  12. Van Heek M, Compton DS, France CF, Tedesco RP, Fawzi AB, Graziano MP, Sybertz EJ, Strader CD, Davis HR Jr (1997) Diet-induced obese mice develop peripheral, but not central, resistance to leptin. J Clin Investig 99(3):385–390. https://doi.org/10.1172/JCI119171

    Article  PubMed  PubMed Central  Google Scholar 

  13. Cole JR, Wang Q, Cardenas E, Fish J, Chai B, Farris RJ, Kulam-Syed-Mohideen AS, McGarrell DM, Marsh T, Garrity GM, Tiedje JM (2009) The Ribosomal Database Project: improved alignments and new tools for rRNA analysis. Nucleic Acids Res 37(database issue):D141–D145. https://doi.org/10.1093/nar/gkn879

    Article  CAS  PubMed  Google Scholar 

  14. Quast C, Pruesse E, Yilmaz P, Gerken J, Schweer T, Yarza P, Peplies J, Glockner FO (2013) The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic Acids Res 41(database issue):D590–D596. https://doi.org/10.1093/nar/gks1219

    Article  CAS  PubMed  Google Scholar 

  15. Schloss PD, Gevers D, Westcott SL (2011) Reducing the effects of PCR amplification and sequencing artifacts on 16S rRNA-based studies. PLoS One 6(12):e27310. https://doi.org/10.1371/journal.pone.0027310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Jiang XT, Peng X, Deng GH, Sheng HF, Wang Y, Zhou HW, Tam NF (2013) Illumina sequencing of 16S rRNA tag revealed spatial variations of bacterial communities in a mangrove wetland. Microb Ecol 66(1):96–104. https://doi.org/10.1007/s00248-013-0238-8

    Article  PubMed  Google Scholar 

  17. Vajro P, Paolella G, Fasano A (2013) Microbiota and gut-liver axis: their influences on obesity and obesity-related liver disease. J Pediatr Gastroenterol Nutr 56(5):461–468. https://doi.org/10.1097/MPG.0b013e318284abb5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Seo M, Inoue I, Tanaka M, Matsuda N, Nakano T, Awata T, Katayama S, Alpers DH, Komoda T (2013) Clostridium butyricum MIYAIRI 588 improves high-fat diet-induced non-alcoholic fatty liver disease in rats. Dig Dis Sci 58(12):3534–3544. https://doi.org/10.1007/s10620-013-2879-3

    Article  PubMed  Google Scholar 

  19. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444(7122):1027–1031. https://doi.org/10.1038/nature05414

    Article  PubMed  Google Scholar 

  20. Ley RE, Backhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI (2005) Obesity alters gut microbial ecology. Proc Natl Acad Sci USA 102(31):11070–11075. https://doi.org/10.1073/pnas.0504978102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Boerner BP, Sarvetnick NE (2011) Type 1 diabetes: role of intestinal microbiome in humans and mice. Ann N Y Acad Sci 1243:103–118. https://doi.org/10.1111/j.1749-6632.2011.06340.x

    Article  CAS  PubMed  Google Scholar 

  22. Daien CI, Pinget GV, Tan JK, Macia L (2017) Detrimental impact of microbiota-accessible carbohydrate-deprived diet on gut and immune homeostasis: an overview. Front Immunol 8:548. https://doi.org/10.3389/fimmu.2017.00548

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Bonder MJ, Kurilshikov A, Tigchelaar EF, Mujagic Z, Imhann F, Vila AV, Deelen P, Vatanen T, Schirmer M, Smeekens SP, Zhernakova DV, Jankipersadsing SA, Jaeger M, Oosting M, Cenit MC, Masclee AA, Swertz MA, Li Y, Kumar V, Joosten L, Harmsen H, Weersma RK, Franke L, Hofker MH, Xavier RJ, Jonkers D, Netea MG, Wijmenga C, Fu J, Zhernakova A (2016) The effect of host genetics on the gut microbiome. Nat Genet 48(11):1407–1412. https://doi.org/10.1038/ng.3663

    Article  CAS  PubMed  Google Scholar 

  24. Wang LL, Guo HH, Huang S, Feng CL, Han YX, Jiang JD (2017) Comprehensive evaluation of SCFA production in the intestinal bacteria regulated by berberine using gas-chromatography combined with polymerase chain reaction. J Chromatogr B Anal Technol Biomed Life Sci 1057:70–80. https://doi.org/10.1016/j.jchromb.2017.05.004

    Article  CAS  Google Scholar 

  25. Albenberg LG, Wu GD (2014) Diet and the intestinal microbiome: associations, functions, and implications for health and disease. Gastroenterology 146(6):1564–1572. https://doi.org/10.1053/j.gastro.2014.01.058

    Article  CAS  PubMed  Google Scholar 

  26. Psichas A, Sleeth ML, Murphy KG, Brooks L, Bewick GA, Hanyaloglu AC, Ghatei MA, Bloom SR, Frost G (2015) The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents. Int J Obes (Lond) 39(3):424–429. https://doi.org/10.1038/ijo.2014.153

    Article  CAS  Google Scholar 

  27. Perry RJ, Peng L, Barry NA, Cline GW, Zhang D, Cardone RL, Petersen KF, Kibbey RG, Goodman AL, Shulman GI (2016) Acetate mediates a microbiome-brain-beta-cell axis to promote metabolic syndrome. Nature 534(7606):213–217. https://doi.org/10.1038/nature18309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Carmen GY, Victor SM (2006) Signalling mechanisms regulating lipolysis. Cell Signal 18(4):401–408. https://doi.org/10.1016/j.cellsig.2005.08.009

    Article  CAS  PubMed  Google Scholar 

  29. 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

    Article  CAS  PubMed  Google Scholar 

  30. Li Y, Fan L, Sun Y, Zhang D, Yue Z, Niu Y, Meng J, Yang T, Liu W, Mei Q (2013) An apple oligogalactan suppresses endotoxin-induced cyclooxygenase-2 expression by inhibition of LPS pathways. Int J Biol Macromol 61:75–81. https://doi.org/10.1016/j.ijbiomac.2013.06.048

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This investigation was supported by the Grant (no. 81302787), from National Natural Science Foundation of China and the Grant (no. 2018M633405) from Postdoctoral Science Foundation of China, and the Grant (no. 2019JQ-562) from Shaanxi Natural Science basic Research Program Project.

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Authors

Contributions

The experiments were conceived and designed by YL, WX, and QM, and performed by YL, WX, YS, YW, YT, YL, XG, and CS; the data were analyzed by WX, YS, and LL. The initial manuscript draft was written by YL, and critically revised by LL and QM. And all authors read and approved the final manuscript.

Corresponding authors

Correspondence to Li Liu or Qibing Mei.

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The authors declare that they have no conflict of interest.

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Li, Y., Xu, W., Sun, Y. et al. Modified apple polysaccharide regulates microbial dysbiosis to suppress high-fat diet-induced obesity in C57BL/6J mice. Eur J Nutr 59, 2025–2037 (2020). https://doi.org/10.1007/s00394-019-02051-z

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