Advertisement

Lipids

, Volume 52, Issue 6, pp 499–511 | Cite as

Short Term High Fat Diet Induces Obesity-Enhancing Changes in Mouse Gut Microbiota That are Partially Reversed by Cessation of the High Fat Diet

  • Yue Shang
  • Ehsan Khafipour
  • Hooman Derakhshani
  • Lindsei K. Sarna
  • Connie W. Woo
  • Yaw L. Siow
  • Karmin OEmail author
Original Article

Abstract

The gut microbiota is proposed as a “metabolic organ” involved in energy utilization and is associated with obesity. Dietary intervention is one of the approaches for obesity management. Changes in dietary components have significant impacts on host metabolism and gut microbiota. In the present study, we examined the influence of dietary fat intervention on the modification of gut mucosa-associated microbiota profile along with body weight and metabolic parameter changes. Male C57BL/6J mice (6-week old) were fed a low fat diet (10% kcal fat) as a control or a high fat diet (HFD 60% kcal fat) for 7 weeks. In another group, mice were fed HFD for 5 weeks followed by low fat control diet for 2 weeks (HFD + Control). At 7 weeks, body weight gain, blood glucose and hepatic triacylglycerol levels of mice fed a HFD were significantly higher than that of the control group and the HFD + Control group. There were significant differences in the diversity and predicted functional properties of microbiota in the cecum and colon mucosa between the control group and the HFD group. HFD feeding reduced the ratio of Bacteroidetes to Firmicutes, a microbiota pattern often associated with obesity. The HFD + Control diet partially restored the diversity and composition of microbiota in the cecum to the pattern observed in mice fed a control diet. These results suggest that short-term high fat diet withdrawal can restore metabolic changes and prevent excess body weight gain, however, long-term dietary intervention may be required to optimize the restoration of gut microbiota in mouse.

Keywords

Dietary fat intervention High fat diet Gut microbiota Mucosa 

Abbreviations

ANOVA

Analysis of variance

GLM

General linear models

HFD

High fat diet

KEGG

Kyoto encyclopedia of genes and genomes

OTU

Operational taxonomic units

PCoA

Principal coordinate analysis

PERMANOVA

Permutational multivariate analysis of variance

PICRUSt

Phylogenetic investigation of communities by reconstruction of unobserved states

QIIME

Quantitative insights into microbial ecology

STAMP

Statistical analysis of metagenomic profiles

Notes

Acknowledgements

This study was supported, in part, by the Natural Sciences and Engineering Research Council of Canada, St. Boniface Hospital Research Centre and University of Manitoba Start-up Grant Program.

Supplementary material

11745_2017_4253_MOESM1_ESM.docx (60 kb)
Supplementary Table 1. Phylogenetic comparisons (level 3) based on KEGG pathways. Significant differences observed by phylogenetic comparisons of cecum and colon mucosa-associated microbiota using KEGG orthology reference pathways (on level 3) between mice fed different types of diets (n = 4 per group) (DOCX 60 kb)
11745_2017_4253_MOESM2_ESM.xlsx (135 kb)
Taxonomy analysis. Raw count data standardized to percentage relative abundance per phylum, class, order, family, and genus of the cecal and colonic microorganisms in each sample (XLSX 135 kb)

References

  1. 1.
    Backhed 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 101:15718–15723CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Evans CC, LePard KJ, Kwak JW, Stancukas MC, Laskowski S, Dougherty J, Moulton L, Glawe A, Wang Y, Leone V, Antonopoulos DA, Smith D, Chang EB, Ciancio MJ (2014) Exercise prevents weight gain and alters the gut microbiota in a mouse model of high fat diet-induced obesity. PLoS One 9:e92193CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Fock KM, Khoo J (2013) Diet and exercise in management of obesity and overweight. J Gastroenterol Hepatol 28(Suppl 4):59–63CrossRefPubMedGoogle Scholar
  4. 4.
    Johns DJ, Lindroos AK, Jebb SA, Sjostrom L, Carlsson LM, Ambrosini GL (2015) Dietary patterns, cardiometabolic risk factors, and the incidence of cardiovascular disease in severe obesity. Obesity 23:1063–1070CrossRefPubMedGoogle Scholar
  5. 5.
    Gardner CD (2012) Tailoring dietary approaches for weight loss. Int J Obes Suppl 2:S11–S15CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Ley RE, Backhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI (2005) Obesity alters gut microbial ecology. Proc Natl Acad Sci USA 102:11070–11075CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    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 444:1027–1031CrossRefPubMedGoogle Scholar
  8. 8.
    Cani PD, Delzenne NM, Amar J, Burcelin R (2008) Role of gut microflora in the development of obesity and insulin resistance following high-fat diet feeding. Pathol Biol 56:305–309CrossRefPubMedGoogle Scholar
  9. 9.
    Ursell LK, Haiser HJ, Van Treuren W, Garg N, Reddivari L, Vanamala J, Dorrestein PC, Turnbaugh PJ, Knight R (2014) The intestinal metabolome: an intersection between microbiota and host. Gastroenterology 146:1470–1476CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Nehra V, Allen JM, Mailing LJ, Kashyap PC, Woods JA (2016) Gut microbiota: modulation of host physiology in obesity. Physiology 31:327–335CrossRefPubMedGoogle Scholar
  11. 11.
    Goodrich JK, Waters JL, Poole AC, Sutter JL, Koren O, Blekhman R, Beaumont M, Van Treuren W, Knight R, Bell JT, Spector TD, Clark AG, Ley RE (2014) Human genetics shape the gut microbiome. Cell 159:789–799CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C, Bindels LB, Guiot Y, Derrien M, Muccioli GG, Delzenne NM, de Vos WM, Cani PD (2013) Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci USA 110:9066–9071CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Cotillard A, Kennedy SP, Kong LC, Prifti E, Pons N, Le Chatelier E, Almeida M, Quinquis B, Levenez F, Galleron N, Gougis S, Rizkalla S, Batto J-M, Renault P, Consortium ANRM, Dore J, Zucker J-D, Clement K, Ehrlich SD, Members ANRMc (2013) Dietary intervention impact on gut microbial gene richness. Nature 500:585–588CrossRefPubMedGoogle Scholar
  14. 14.
    Daniel H, Moghaddas Gholami A, Berry D, Desmarchelier C, Hahne H, Loh G, Mondot S, Lepage P, Rothballer M, Walker A, Bohm C, Wenning M, Wagner M, Blaut M, Schmitt-Kopplin P, Kuster B, Haller D, Clavel T (2014) High-fat diet alters gut microbiota physiology in mice. ISME J 8:295–308CrossRefPubMedGoogle Scholar
  15. 15.
    Turnbaugh PJ, Backhed F, Fulton L, Gordon JI (2008) Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe 3:213–223CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Ellekilde M, Selfjord E, Larsen CS, Jakesevic M, Rune I, Tranberg B, Vogensen FK, Nielsen DS, Bahl MI, Licht TR, Hansen AK, Hansen CHF (2014) Transfer of gut microbiota from lean and obese mice to antibiotic-treated mice. Sci Rep 4:5922CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Zhang C, Zhang M, Pang X, Zhao Y, Wang L, Zhao L (2012) Structural resilience of the gut microbiota in adult mice under high-fat dietary perturbations. ISME J 6:1848–1857CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Sid V, Wu N, Sarna LK, Siow YL, House JD, O K (2015) Folic acid supplementation during high-fat diet feeding restores AMPK activation via an AMP-LKB1-dependent mechanism. Am J Physiol Regul Integr Comp Physiol 309:R1215–R1225PubMedPubMedCentralGoogle Scholar
  19. 19.
    Sarna LK, Sid V, Wang P, Siow YL, House JD, O K (2016) Tyrosol attenuates high fat diet-induced hepatic oxidative stress: potential involvement of cystathionine β-synthase and cystathionine γ-lyase. Lipids 51:583–590CrossRefPubMedGoogle Scholar
  20. 20.
    CCAC (1993) Guide to the care and use of experimental animals. Ottawa, OntarioGoogle Scholar
  21. 21.
    Khafipour E, Li S, Plaizier JC, Krause DO (2009) Rumen microbiome composition determined using two nutritional models of subacute ruminal acidosis. Appl Environ Microbiol 75:7115–7124CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Derakhshani H, Tun HM, Khafipour E (2016) An extended single-index multiplexed 16S rRNA sequencing for microbial community analysis on MiSeq illumina platforms. J Basic Microbiol 56:321–326CrossRefPubMedGoogle Scholar
  23. 23.
    Caporaso JG, Lauber CL, Walters WA, Berg-Lyons D, Huntley J, Fierer N, Owens SM, Betley J, Fraser L, Bauer M (2012) Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms. ISME J 6:1621–1624CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, Fierer N, Pena AG, Goodrich JK, Gordon JI (2010) QIIME allows analysis of high-throughput community sequencing data. Nat Methods 7:335–336CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Edgar RC, Haas BJ, Clemente JC, Quince C, Knight R (2011) UCHIME improves sensitivity and speed of chimera detection. Bioinformatics 27:2194–2200CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Edgar RC (2010) Search and clustering orders of magnitude faster than BLAST. Bioinformatics 26:2460–2461CrossRefPubMedGoogle Scholar
  27. 27.
    Wang Q, Garrity GM, Tiedje JM, Cole JR (2007) Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy. Appl Environ Microbiol 73:5261–5267CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    DeSantis TZ, Hugenholtz P, Larsen N, Rojas M, Brodie EL, Keller K, Huber T, Dalevi D, Hu P, Andersen GL (2006) Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB. Appl Environ Microbiol 72:5069–5072CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Caporaso JG, Bittinger K, Bushman FD, DeSantis TZ, Andersen GL, Knight R (2010) PyNAST: a flexible tool for aligning sequences to a template alignment. Bioinformatics 26:266–267CrossRefPubMedGoogle Scholar
  30. 30.
    Lozupone C, Knight R (2005) UniFrac: a new phylogenetic method for comparing microbial communities. Appl Environ Microbiol 71:8228–8235CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Warwick R, Clarke K (2006) PRIMER 6. PRIMER-E Ltd, PlymouthGoogle Scholar
  32. 32.
    Li R, Khafipour E, Krause DO, Entz MH, de Kievit TR, Fernando WD (2012) Pyrosequencing reveals the influence of organic and conventional farming systems on bacterial communities. PLoS One 7:e51897CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Langille MG, Zaneveld J, Caporaso JG, McDonald D, Knights D, Reyes JA, Clemente JC, Burkepile DE, Vega Thurber RL, Knight R, Beiko RG, Huttenhower C (2013) Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nat Biotechnol 31:814–821CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Kanehisa M, Goto S, Kawashima S, Okuno Y, Hattori M (2004) The KEGG resource for deciphering the genome. Nucleic Acids Res 32:D277–D280CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Parks DH, Tyson GW, Hugenholtz P, Beiko RG (2014) STAMP: statistical analysis of taxonomic and functional profiles. Bioinformatics 30:3123–3124CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Daniel H, Moghaddas Gholami A, Berry D, Desmarchelier C, Hahne H, Loh G, Mondot S, Lepage P, Rothballer M, Walker A, Bohm C, Wenning M, Wagner M, Blaut M, Schmitt-Kopplin P, Kuster B, Haller D, Clavel T (2014) High-fat diet alters gut microbiota physiology in mice. ISME J 8:295–308CrossRefPubMedGoogle Scholar
  37. 37.
    Ley RE, Backhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI (2005) Obesity alters gut microbial ecology. Proc Natl Acad Sci USA 102:11070–11075CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Lecomte V, Kaakoush NO, Maloney CA, Raipuria M, Huinao KD, Mitchell HM, Morris MJ (2015) Changes in gut microbiota in rats fed a high fat diet correlate with obesity-associated metabolic parameters. PLoS One 10:e0126931CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Turnbaugh PJ, Backhed F, Fulton L, Gordon JI (2008) Marked alterations in the distal gut microbiome linked to diet-induced obesity. Cell Host Microbe 3:213–223CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Clarke SF, Murphy EF, Nilaweera K, Ross PR, Shanahan F, O’Toole PW, Cotter PD (2014) The gut microbiota and its relationship to diet and obesity. Gut Microbes 3:186–202CrossRefGoogle Scholar
  41. 41.
    Walker AW, Ince J, Duncan SH, Webster LM, Holtrop G, Ze X, Brown D, Stares MD, Scott P, Bergerat A, Louis P, McIntosh F, Johnstone AM, Lobley GE, Parkhill J, Flint HJ (2011) Dominant and diet-responsive groups of bacteria within the human colonic microbiota. ISME J 5:220–230CrossRefPubMedGoogle Scholar
  42. 42.
    Duncan SH, Belenguer A, Holtrop G, Johnstone AM, Flint HJ, Lobley GE (2007) Reduced dietary intake of carbohydrates by obese subjects results in decreased concentrations of butyrate and butyrate-producing bacteria in feces. Appl Environ Microbiol 73:1073–1078CrossRefPubMedGoogle Scholar
  43. 43.
    Haange S-B, Oberbach A, Schlichting N, Hugenholtz F, Smidt H, von Bergen M, Till H, Seifert J (2012) Metaproteome analysis and molecular genetics of rat intestinal microbiota reveals section and localization resolved species distribution and enzymatic functionalities. J Proteome Res 11:5406–5417CrossRefPubMedGoogle Scholar
  44. 44.
    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 505:559–563CrossRefPubMedGoogle Scholar
  45. 45.
    Barcenilla A, Pryde SE, Martin JC, Duncan SH, Stewart CS, Henderson C, Flint HJ (2000) Phylogenetic relationships of butyrate-producing bacteria from the human gut. Appl Environ Microbiol 66:1654–1661CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C, Waget A, Delmée E, Cousin B, Sulpice T, Chamontin B, Ferrières J, Tanti J-F, Gibson GR, Casteilla L, Delzenne NM, Alessi MC, Burcelin R (2007) Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56:1761–1772CrossRefPubMedGoogle Scholar
  47. 47.
    Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, Burcelin R (2008) Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 57:1470–1481CrossRefPubMedGoogle Scholar
  48. 48.
    Meehan CJ, Beiko RG (2014) A phylogenomic view of ecological specialization in the Lachnospiraceae, a family of digestive tract-associated bacteria. Genome Biol Evol 6:703–713CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Singh V, Chassaing B, Zhang L, San Yeoh B, Xiao X, Kumar M, Baker MT, Cai J, Walker R, Borkowski K, Harvatine KJ, Singh N, Shearer GC, Ntambi JM, Joe B, Patterson AD, Gewirtz AT, Vijay-Kumar M (2015) Microbiota-dependent hepatic lipogenesis mediated by stearoyl CoA desaturase 1 (SCD1) promotes metabolic syndrome in TLR5-deficient mice. Cell Metab 22:983–996CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Fernandes J, Su W, Rahat-Rozenbloom S, Wolever TM, Comelli EM (2014) Adiposity, gut microbiota and faecal short chain fatty acids are linked in adult humans. Nutr Diabetes 4:e121CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Venema K (2010) Role of gut microbiota in the control of energy and carbohydrate metabolism. Curr Opin Clin Nutr Metab Care 13:432–438CrossRefPubMedGoogle Scholar
  52. 52.
    Ibrahim M, Anishetty S (2012) A meta-metabolome network of carbohydrate metabolism: interactions between gut microbiota and host. Biochem Biophys Res Commun 428:278–284CrossRefPubMedGoogle Scholar
  53. 53.
    Hildebrandt MA, Hoffmann C, Sherrill-Mix SA, Keilbaugh SA, Hamady M, Chen YY, Knight R, Ahima RS, Bushman F, Wu GD (2009) High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology 137(1716–1724):e1711–e1712Google Scholar
  54. 54.
    Nguyen TLA, Vieira-Silva S, Liston A, Raes J (2015) How informative is the mouse for human gut microbiota research? Dis Models Mech 8:1–16CrossRefGoogle Scholar
  55. 55.
    Xiao L, Feng Q, Liang S, Sonne SB, Xia Z, Qiu X, Li X, Long H, Zhang J, Zhang D, Liu C, Fang Z, Chou J, Glanville J, Hao Q, Kotowska D, Colding C, Licht TR, Wu D, Yu J, Sung JJY, Liang Q, Li J, Jia H, Lan Z, Tremaroli V, Dworzynski P, Nielsen HB, Backhed F, Dore J, Le Chatelier E, Ehrlich SD, Lin JC, Arumugam M, Wang J, Madsen L, Kristiansen K (2015) A catalog of the mouse gut metagenome. Nat Biotech 33:1103–1108CrossRefGoogle Scholar
  56. 56.
    Murphy EF, Cotter PD, Healy S, Marques TM, O’Sullivan O, Fouhy F, Clarke SF, O’Toole PW, Quigley EM, Stanton C, Ross PR, O’Doherty RM, Shanahan F (2010) Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models. Gut 59:1635–1642CrossRefPubMedGoogle Scholar
  57. 57.
    Turnbaugh PJ, Ridaura VK, Faith JJ, Rey FE, Knight R, Gordon JI (2009) The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci Transl Med 1:6ra14–16ra14CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© AOCS 2017

Authors and Affiliations

  • Yue Shang
    • 1
    • 2
  • Ehsan Khafipour
    • 2
    • 3
  • Hooman Derakhshani
    • 2
  • Lindsei K. Sarna
    • 1
    • 2
  • Connie W. Woo
    • 4
  • Yaw L. Siow
    • 1
    • 5
    • 6
  • Karmin O
    • 1
    • 2
    • 6
    Email author
  1. 1.Laboratory of Integrative Biology, CCARMSt. Boniface Hospital Research CentreWinnipegCanada
  2. 2.Department of Animal ScienceWinnipegCanada
  3. 3.Department of Medical MicrobiologyUniversity of ManitobaWinnipegCanada
  4. 4.Department of Pharmacology and PharmacyUniversity of Hong KongHong KongChina
  5. 5.Agriculture and Agri-Food CanadaWinnipegCanada
  6. 6.Department of Physiology and PathophysiologyUniversity of ManitobaWinnipegCanada

Personalised recommendations