High-Fat Diet Determines the Composition of the Murine Gut Microbiome Independently of Obesity
Open accessAbstract
Background & aims The composition of the gut microbiome is affected by host phenotype, genotype, immune function, and diet. Here, we used the phenotype of RELMbeta knockout (KO) mice to assess the influence of these factors.Methods Both wild-type and RELMbeta KO mice were lean on a standard chow diet, but, upon switching to a high-fat diet, wild-type mice became obese, whereas RELMbeta KO mice remained comparatively lean. To investigate the influence of diet, genotype, and obesity on microbiome composition, we used deep sequencing to characterize 25,790 16S rDNA sequences from uncultured bacterial communities from both genotypes on both diets.Results We found large alterations associated with switching to the high-fat diet, including a decrease in Bacteroidetes and an increase in both Firmicutes and Proteobacteria. This was seen for both genotypes (ie, in the presence and absence of obesity), indicating that the high-fat diet itself, and not the obese state, mainly accounted for the observed changes in the gut microbiota. The RELMbeta genotype also modestly influenced microbiome composition independently of diet. Metagenomic analysis of 537,604 sequence reads documented extensive changes in gene content because of a high-fat diet, including an increase in transporters and 2-component sensor responders as well as a general decrease in metabolic genes. Unexpectedly, we found a substantial amount of murine DNA in our samples that increased in proportion on a high-fat diet.Conclusions These results demonstrate the importance of diet as a determinant of gut microbiome composition and suggest the need to control for dietary variation when evaluating the composition of the human gut microbiome.
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Administration of a high-fat diet to healthy subjects caused a decrease in Bacteroidetes levels with an increase in both Firmicutes and Proteobacteria levels of gut microbiota.
“administration of an HFD to healthy subjects caused a decrease in Bacteroidetes levels with an increase in both Firmicutes and Proteobacteria levels of gut microbiota (Hildebrandt et al., 2009;Zhang et al., 2012a).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Hildebrandt et al., 2009
The Results section ('Metagenomic analysis of gut bacterial populations from mice on standard chow or high fat diets'; page not provided) reports increased Proteobacteria and Firmicutes and decreased Bacteroidetes after a switch to a high-fat diet. The study examined mice, however, so it does not establish this effect in human subjects if 'healthy subjects' refers to people. (LLM, conf=0.87)
Experimental — accuracy not yet measuredAnimal models fed a high-fat diet demonstrated an alteration in gut microbiota profile with a reduction in Bacteroidetes levels and an increase in both Proteobacteria and Firmicutes levels.
“animal models fed an HFD demonstrated an alteration in their gut microbiota profile with a reduction in Bacteroidetes levels and an increase in both Proteobacteria and Firmicute levels (Hildebrandt et al., 2009).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Hildebrandt et al., 2009
A diet high in protein and fat (with reduced carbohydrates) has been previously associated with an increase in Firmicutes to Bacteriodetes ratio in mice.
“Those with cystic fibrosis are recommended to consume a diet high in protein and fat (and therefore a comparative reduction in carbohydrates) which has been previously associated with an increase in Firmicutes to Bacteriodetes ratio in mice [96], though dietary data was not collected within the cystic fibrosis study [95].”
From Effect of Diet on the Gut Microbiota: Rethinking Intervention Duration (2019) · cites this paper as [96]
These high-fat diet-induced microbiota changes were observed in mice resistant to weight gain, implying a direct effect of dietary lipids on the microbiota.
“These changes were observed in mice resistant to weight gain, implying a direct effect of dietary lipids on the microbiota (26, 27).”
From The gut microbiota at the intersection of diet and human health (2018) · cites this paper as [26]
Experimental mice fed a high-fat diet (40 to 80% total caloric intake) exhibit decreases in Bacteroidetes and increases in Firmicutes and Proteobacteria.
“Experimental mice fed a high-fat diet (40 to 80% total caloric intake) exhibit decreases at the phyla-level in Bacteroidetes and increases in Firmicutes and Proteobacteria.”
From The gut microbiota at the intersection of diet and human health (2018) · cites this paper as [26]
A high-fat diet, independent of obesity, altered the composition of the intestinal microbiome.
“a high-fat diet, independent of obesity, altered the composition of the intestinal microbiome (Hildebrandt, 2009).”
From Viral Infections, the Microbiome, and Probiotics (2021) · cites this paper as Hildebrandt, 2009
High-fat diets in animal studies reproducibly change gut microbial community structure, decreasing overall microbiota diversity and beneficial bacteria and increasing the Firmicutes:Bacteroidetes ratio and abundance of Enterobacteriales, Clostridium cluster XVIa, Mollicutes, and B. wadsworthia.
“Similar to the Western diet, high-fat diets in animal studies reproducibly change gut microbial community structure, decreasing the overall microbiota diversity and beneficial bacteria (e.g., A. muciniphila, Bifidobacterium, Lactobacillus, and Lactococcus) and increasing the Firmicutes:Bacteroidetes ratio and the abundance of Enterobacteriales, Clostridium cluster XVIa, Mollicutes, and B. wadswort”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [90]
Participants were provided with a non-sugar sweetened, low-fat diet throughout the three meals, except the OGTT, to isolate the solitary impact of sleep on the microbiota.
“To further isolate the solitary impact of sleep on the microbiota – separate from the previously documented impact of e.g. high-fat diet [32] – participants were provided with a non-sugar sweetened, low-fat diet throughout the three meals, the exception being the oral glucose tolerance (OGTT) test on day 2”
From Gut microbiota and glucometabolic alterations in response to recurrent partial sleep deprivation in normal-weight young individuals (2016) · cites this paper as [32]
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Impacts of gut bacteria on human health and diseases
Zhang, Y.-J., Li, S., Gan, R.-Y., Zhou, T., Xu, D.-P., & Li, H.-B. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms16047493 · Cited by 1,055 · see citing works
“In that study, fermentation of polyphenols increased proliferation of Bifidobacteria and decreased the ratio of Firmicutes to Bacteroidetes, compared to controls.”
BackgroundInfluentialConserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity
Liou, A. P., Paziuk, M., Luevano, J.-M., Machineni, S., Turnbaugh, P. J., & Kaplan, L. M. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005687 · Cited by 1,007 · see citing works
Everard, A., Lazarevic, V., Derrien, M., Girard, M., Muccioli, G. G., Neyrinck, A. M., Possemiers, S., Van Holle, A., François, P., de Vos, W. M., et al. (2011) · Diabetes · doi:10.2337/db11-0227 · Cited by 1,076 · see citing works
“Importantly, several other studies have already characterized the gut microbiota composition of ob/ob and diet-induced obese mice by using similar metagenomic approaches (2,12,18,36,40,41).”
BackgroundMethodBile Acid Is a Host Factor That Regulates the Composition of the Cecal Microbiota in Rats
Islam, K. B. M. S., Fukiya, S., Hagio, M., Fujii, N., Ishizuka, S., Ooka, T., Ogura, Y., Hayashi, T., & Yokota, A. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.07.046 · Cited by 918 · see citing works
de La Serre, C. B., Ellis, C. L., Lee, J., Hartman, A. L., Rutledge, J. C., & Raybould, H. E. (2010) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00098.2010 · Cited by 949 · see citing works
“These data are in agreement with that published recently using mice null for RELM , a goblet cell-specific gene whose expression in dependent in gut microbiota and involved in Th2 cytokine-immune signaling that renders mice susceptible to intestinal inflammation (21).”
BackgroundResultInfluentialMurphy, E. F., Cotter, P. D., Healy, S., Marques, T. M., O’Sullivan, Ó., Fouhy, F., Clarke, S. F., O’Toole, P. W., Quigley, E. M. M., Stanton, C., et al. (2010) · Gut · doi:10.1136/gut.2010.215665 · Cited by 942 · see citing works
Diet and feeding pattern affect the diurnal dynamics of the gut microbiome
Zarrinpar, A., Chaix, A., Yooseph, S., & Panda, S. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.11.008 · Cited by 926 · see citing works
Microbiota Regulate Intestinal Absorption and Metabolism of Fatty Acids in the Zebrafish
Semova, I., Carten, J. D., Stombaugh, J., Mackey, L. C., Knight, R. D., Farber, S. A., & Rawls, J. F. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2012.08.003 · Cited by 881 · see citing works
“…diet (Jumpertz et al., 2011), hyperphagic obese ob/ob mice (Ley et al., 2005), mice fed high-calorie Western diets (Turnbaugh et al., 2008; Hildebrandt et al., 2009; Murphy et al., 2010), and postprandial pythons (Costello et al., 2010) assemble gut microbial communities with an…”
BackgroundSelf-citationEffects of gut microbes on nutrient absorption and energy regulation
Krajmalnik‐Brown, R., Ilhan, Z., Kang, D., & DiBaise, J. K. (2012) · Nutrition in Clinical Practice · doi:10.1177/0884533611436116 · Cited by 852 · see citing works
Diet-microbiota interactions and personalized nutrition
Kolodziejczyk, A. A., Zheng, D., & Elinav, E. (2019) · Nature Reviews Microbiology · doi:10.1038/s41579-019-0256-8 · Cited by 879 · see citing works
US immigration westernizes the human gut microbiome
Vangay, P., Johnson, A. J., Ward, T. L., Al-Ghalith, G. A., Shields-Cutler, R. R., Hillmann, B. M., Lucas, S. K., Beura, L. K., Thompson, E. A., Till, L. M., et al. (2018) · Cell · doi:10.1016/j.cell.2018.10.029 · Cited by 794 · see citing works
“The gut microbiome plays a critical role in host metabolism and is heavily influenced by an individual’s long-term diet (Hildebrandt et al., 2009; Wu et al., 2011) and can also respond quickly to dramatic dietary changes (David et al.”
BackgroundBäckhed, F., Fraser, C. M., Ringel, Y., Sanders, M. E., Sartor, R. B., Sherman, P. M., Versalovic, J., Young, V., & Finlay, B. B. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2012.10.012 · Cited by 836 · see citing works
Cani, P. D., Osto, M., Geurts, L., & Everard, A. (2012) · Gut Microbes · doi:10.4161/gmic.19625 · Cited by 864 · see citing works
“showed decreased Bacteriodetes and increased Firmicutes and Proteobacteria in mice fed a high-fat diet.(41) Murphy et al.”
BackgroundGut microbiome, obesity, and metabolic dysfunction
Tilg, H., & Kaser, A. (2011) · Journal of Clinical Investigation · doi:10.1172/jci58109 · Cited by 860 · see citing works
Chelakkot, C., Choi, Y., Kim, D., Park, H. T., Ghim, J., Kwon, Y., Jeon, J., Kim, M.-S., Jee, Y., Gho, Y. S., et al. (2018) · Experimental & Molecular Medicine · doi:10.1038/emm.2017.282 · Cited by 852 · see citing works
Microbiota-Brain-Gut Axis and Neurodegenerative Diseases
Quigley, E. M. M. (2017) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-017-0802-6 · Cited by 804 · see citing works
Effect of Diet on the Gut Microbiota: Rethinking Intervention Duration
Leeming, E. R., Johnson, A. J., Spector, T. D., & Le Roy, C. I. (2019) · Nutrients · doi:10.3390/nu11122862 · Cited by 817 · see citing works
“Those with cystic fibrosis are recommended to consume a diet high in protein and fat (and therefore a comparative reduction in carbohydrates) which has been previously associated with an increase in Firmicutes to Bacteriodetes ratio in mice [96], though dietary data was not collected within the cystic fibrosis study […”
BackgroundGut-liver axis: Pathophysiological concepts and clinical implications
Tilg, H., Adolph, T. E., & Trauner, M. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.09.017 · Cited by 843 · see citing works
Schneeberger, M., Everard, A., Gómez-Valadés, A. G., Matamoros, S., Ramírez, S., Delzenne, N. M., Gomis, R., Claret, M., & Cani, P. D. (2015) · Scientific Reports · doi:10.1038/srep16643 · Cited by 798 · see citing works
High-Fat, Western-Style Diet, Systemic Inflammation, and Gut Microbiota: A Narrative Review
Malesza, I. J., Malesza, M., Walkowiak, J., Mussin, N. M., Walkowiak, D., Aringazina, R. A., Bartkowiak-Wieczorek, J., & Mądry, E. (2021) · Cells · doi:10.3390/cells10113164 · Cited by 807 · see citing works
Targeting gut microbiota in obesity: effects of prebiotics and probiotics
Delzenne, N. M., Neyrinck, A. M., Bäckhed, F., & Cani, P. D. (2011) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2011.126 · Cited by 783 · see citing works
Impact of Omega-3 Fatty Acids on the Gut Microbiota
Costantini, L., Molinari, R., Farinon, B., & Merendino, N. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18122645 · Cited by 741 · see citing works
“(2009) [38] C57BL/6 and β resistin-like molecule β knockout mice High-fat diet (45% fat) for 21 weeks High fat diet caused changed in microbiota composition with a decrease in Bacteroidetes phylum and an increase in both Firmicutes and Proteobacteria phyla.”
BackgroundMethodInfluentialSchroeder, B. O., Birchenough, G. M. H., Ståhlman, M., Arike, L., Johansson, M. E. V., Hansson, G. C., & Bäckhed, F. (2018) · Cell Host & Microbe · doi:10.1016/j.chom.2017.11.004 · Cited by 713 · see citing works
“Similar to previous studies (Hildebrandt et al., 2009; Turnbaugh et al., 2008, 2009), we observed increased abundance of taxa belonging to Firmicutes and reduced abundance of Bacteroidetes and Actinobacteria in the colonic lumen of mice fed a WSD (Figure 3A and Table S1).”
ResultIntestinal microbiota in human health and disease: the impact of probiotics
Gerritsen, J., Smidt, H., Rijkers, G. T., & de Vos, W. M. (2011) · Genes & Nutrition · doi:10.1007/s12263-011-0229-7 · Cited by 724 · see citing works
“Recent studies in mice show that the influence of the diet (high-fat vs. standard chow or low-fat) on the composition of the intestinal microbiota is independent of genetic disposition for obesity (Hildebrandt et al. 2009; Murphy et al. 2010).”
BackgroundMichielan, A., & D’Incà, R. (2015) · Mediators of Inflammation · doi:10.1155/2015/628157 · Cited by 709 · see citing works
“Western diet with its high content of fat and refined sugars is a risk factor for the development of CD [109] probably inducing a low-grade inflammation via gut dysbiosis and increased intestinal permeability [110–112].”
BackgroundDing, S., Chi, M. M., Scull, B. P., Rigby, R., Schwerbrock, N. M. J., Magness, S., Jobin, C., & Lund, P. K. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012191 · Cited by 713 · see citing works
“Similarly a recent study demonstrated that HF diet altered the composition of luminal bacteria in mice genetically engineered to be resistant to obesity [19].”
BackgroundDiet-Induced Dysbiosis of the Intestinal Microbiota and the Effects on Immunity and Disease
Brown, K., DeCoffe, D., Molcan, E., & Gibson, D. L. (2012) · Nutrients · doi:10.3390/nu4081095 · Cited by 682 · see citing works
“δ-Proteobacteria Increased [61] Animal milk fat δ-Proteobacteria Increased [62]”
BackgroundFood Components and Dietary Habits: Keys for a Healthy Gut Microbiota Composition
Rinninella, E., Cintoni, M., Raoul, P. C., Lopetuso, L. R., Scaldaferri, F., Pulcini, G., Miggiano, G. A. D., Gasbarrini, A., & Mele, M. C. (2019) · Nutrients · doi:10.3390/nu11102393 · Cited by 678 · see citing works
“Interestingly, these changes may be gradually reverted by a control diet [68,69].”
BackgroundObesity, Diabetes, and Gut Microbiota
Musso, G., Gambino, R., & Cassader, M. (2010) · Diabetes Care · doi:10.2337/dc10-0556 · Cited by 662 · see citing works
“(12) employed the resistin-like molecule(RELM- ) KO mice, a model that is resistant to high-fat–induced obesity.”
MethodInsights into the role of the microbiome in obesity and type 2 diabetes
Hartstra, A. V., Bouter, K. E. C., Bäckhed, F., & Nieuwdorp, M. (2015) · Diabetes Care · doi:10.2337/dc14-0769 · Cited by 641 · see citing works
The Origins and Drivers of Insulin Resistance
Johnson, A. M. F., & Olefsky, J. M. (2013) · Cell · doi:10.1016/j.cell.2013.01.041 · Cited by 639 · see citing works
Antibiotics as deep modulators of gut microbiota: between good and evil
Ianiro, G., Tilg, H., & Gasbarrini, A. (2016) · Gut · doi:10.1136/gutjnl-2016-312297 · Cited by 629 · see citing works
“114 Recently, two metagenome-wide association studies, respectively from China 115 and Europe, 116 addressed microbiota composition in patients with T2D: despite population-speci fi c changes, several common fi ndings, including a decrease in butyrate producers (including Roseburia intestinalis and F…”
BackgroundMicrobiome of prebiotic-treated mice reveals novel targets involved in host response during obesity
Everard, A., Lazarevic, V., Gaïa, N., Johansson, M., Ståhlman, M., Backhed, F., Delzenne, N. M., Schrenzel, J., François, P., & Cani, P. D. (2014) · The ISME Journal · doi:10.1038/ismej.2014.45 · Cited by 598 · see citing works
Liu, B., Liu, X., Liang, Z., & Wang, J. (2021) · World Journal of Gastroenterology · doi:10.3748/wjg.v27.i25.3837 · Cited by 625 · see citing works
Interaction of dietary compounds, especially polyphenols, with the intestinal microbiota: a review
Duda-Chodak, A., Tarko, T., Satora, P., & Sroka, P. (2015) · European Journal of Nutrition · doi:10.1007/s00394-015-0852-y · Cited by 599 · see citing works
Cullin, N., Azevedo Antunes, C., Straussman, R., Stein-Thoeringer, C. K., & Elinav, E. (2021) · Cancer Cell · doi:10.1016/j.ccell.2021.08.006 · Cited by 578 · see citing works
“Switching to a high-fat diet increases the prevalence of Firmicutes and Proteobacteria, while decreasing the abundance of Bacteroidetes (Hildebrandt et al., 2009) and activating NF-kB inflammatory pathways in mice, which correlates with cancer onset (Kim et al.”
BackgroundInteractions Between Gut Microbiota and Host Metabolism Predisposing to Obesity and Diabetes
Musso, G., Gambino, R., & Cassader, M. (2011) · Annual Review of Medicine · doi:10.1146/annurev-med-012510-175505 · Cited by 598 · see citing works
“When RELMβ KO and RELMβ wild-type mice were switched from a standard diet to a high-fat diet, both groups underwent similar changes in gut microbiota composition, indicating that effects of diet dominated over the obese phenotype (17).”
MethodEvans, C. C., LePard, K. J., Kwak, J. W., Stancukas, M. C., Laskowski, S., Dougherty, J., Moulton, L., Glawe, A., Wang, Y., Leone, V., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0092193 · Cited by 587 · see citing works
“Moreover, the obese-associated gut microbiota have increased capacity for energy harvest from ingested food [10] and when weight gain is controlled in the design, it is the HF diet, not body fatness, that determines whether a gut microbiota shift occurs [14].”
BackgroundSpencer, M. D., Hamp, T. J., Reid, R. W., Fischer, L. M., Zeisel, S. H., & Fodor, A. A. (2011) · Gastroenterology · doi:10.1053/j.gastro.2010.11.049 · Cited by 593 · see citing works
Verdam, F. J., Fuentes, S., de Jonge, C., Zoetendal, E. G., Erbil, R., Greve, J. W., Buurman, W. A., de Vos, W. M., & Rensen, S. S. (2013) · Obesity · doi:10.1002/oby.20466 · Cited by 587 · see citing works
“Some of these have recently been described to be increased in mice on a high fat diet (19).”
BackgroundDiabetes, obesity and gut microbiota
Everard, A., & Cani, P. D. (2013) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/j.bpg.2013.03.007 · Cited by 546 · see citing works
Martinez-Medina, M., Denizot, J., Dreux, N., Robin, F., Billard, E., Bonnet, R., Darfeuille-Michaud, A., & Barnich, N. (2014) · Gut · doi:10.1136/gutjnl-2012-304119 · Cited by 539 · see citing works
Interactions Between the Host Innate Immune System and Microbes in Inflammatory Bowel Disease
Abraham, C., & Medzhitov, R. M. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.02.012 · Cited by 537 · see citing works
Gut microbiota and metabolic syndrome
Festi, D., Schiumerini, R., Eusebi, L. H., Marasco, G., Taddia, M., & Colecchia, A. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i43.16079 · Cited by 534 · see citing works
Effects of Psychological, Environmental and Physical Stressors on the Gut Microbiota
Karl, J. P., Hatch‐McChesney, A., Arcidiacono, S. M., Pearce, S., Pantoja-Feliciano, I. G., Doherty, L. A., & Soares, J. W. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.02013 · Cited by 535 · see citing works
Wu, G. D., Compher, C., Chen, E. Z., Smith, S. A., Shah, R. D., Bittinger, K., Chehoud, C., Albenberg, L. G., Nessel, L., Gilroy, E., et al. (2016) · Gut · doi:10.1136/gutjnl-2014-308209 · Cited by 512 · see citing works
Self-citationCaptivity humanizes the primate microbiome
Clayton, J. B., Vangay, P., Huang, H., Ward, T., Hillmann, B., Al‐Ghalith, G. A., Travis, D. A., Long, H. T., Tuan, B. V., Minh, V. V., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1521835113 · Cited by 510 · see citing works
Phytochemicals as antibiotic alternatives to promote growth and enhance host health
Lillehoj, H., Liu, Y., Calsamiglia, S., Fernandez-Miyakawa, M. E., Chi, F., Cravens, R. L., Oh, S., & Gay, C. G. (2018) · Veterinary Research · doi:10.1186/s13567-018-0562-6 · Cited by 515 · see citing works
Liou, J., Malfertheiner, P., Lee, Y., Sheu, B., Sugano, K., Cheng, H., Yeoh, K. G., Hsu, P.-I., Goh, K., Mahachai, V., et al. (2020) · Gut · doi:10.1136/gutjnl-2020-322368 · Cited by 501 · see citing works
The gut microbiota, obesity and insulin resistance
Shen, J., Obin, M. S., & Zhao, L. (2013) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2012.11.001 · Cited by 599 · see citing works
“Importantly, similar HFD-induced changes in gut bacterial composition were noted for wild-type and RELMbeta KO mice (Hildebrandt et al., 2009), suggesting that diet, rather than the obese phenotype, plays a dominant role in shaping the bacterial composition of the gut microbiota.”
BackgroundExploring host–microbiota interactions in animal models and humansPreprint
Kostic, A. D., Howitt, M. R., & Garrett, W. S. (2013) · Genes & Development · doi:10.1101/gad.212522.112 · Cited by 491 · see citing works
“Dietary interventions in mouse models have been the topic of several outstanding recent reviews and papers, and mice have been an excellent model to examine intersections of the microbiome, diet, genetics, and obesity and metabolic syndrome as well as intestinal inflammation (Ley et al. 2005; Turnbaugh et al. 2006, 20…”
Zhao, L., Zhang, Q., Ma, W., Tian, F., Shen, H., & Zhou, M. (2017) · Food & Function · doi:10.1039/c7fo01383c · Cited by 492 · see citing works
Influence of high-fat diet on gut microbiota
Murphy, E. A., Velázquez, K. T., & Herbert, K. (2015) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000209 · Cited by 495 · see citing works
“All rights rese modifications in the gut microbial profile as well as decreased diversity [2,3].”
BackgroundRivas, M. N., Burton, O. T., Wise, P. M., Zhang, Y., Hobson, S. A., Lloret, M. G., Chehoud, C., Kuczynski, J., DeSantis, T. Z., Warrington, J. A., et al. (2012) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2012.10.026 · Cited by 488 · see citing works
The function of our microbiota: who is out there and what do they do?
Ottman, N., Smidt, H., de Vos, W. M., & Belzer, C. (2012) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2012.00104 · Cited by 485 · see citing works
Intestinal microbiota, diet and health
Power, S. E., O'Toole, P. W., Stanton, C., Ross, R. P., & Fitzgerald, G. F. (2014) · British Journal Of Nutrition · doi:10.1017/s0007114513002560 · Cited by 476 · see citing works
“Hildebrandt et al. (68) also found distinctive changes in the abundance of the gut microbiota of mice following a switch from a standard chow to a high-fat diet, which was associated with a proportional decrease in the abundance of bacteria of the phylum Bacteroidetes and an increase in that of…”
Agus, A., Denizot, J., Thévenot, J., Martinez-Medina, M., Massier, S., Sauvanet, P., Bernalier-Donadille, A., Denis, S., Hofman, P., Bonnet, R., et al. (2016) · Scientific Reports · doi:10.1038/srep19032 · Cited by 477 · see citing works
Role of Dietary Nutrients in the Modulation of Gut Microbiota: A Narrative Review
Yang, Q., Liang, Q., Balakrishnan, B., Belobrajdic, D. P., Feng, Q.-J., & Zhang, W. Y. (2020) · Nutrients · doi:10.3390/nu12020381 · Cited by 475 · see citing works
Neyrinck, A. M., Possemiers, S., Druart, C., Van de Wiele, T., De Backer, F., Cani, P. D., Larondelle, Y., & Delzenne, N. M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020944 · Cited by 465 · see citing works
“A shift in the composition the murine gut microbiota, such as a decrease in Bacteroidetes or an increase in Firmicutes, was reported to be induced by dietary interventions in favour of a HF diet [3,28,38].”
BackgroundHildebrand, F., Nguyen, T. L. A., Brinkman, B. M. N., Yunta, R. G., Cauwe, B., Vandenabeele, P., Liston, A., & Raes, J. (2013) · Genome biology · doi:10.1186/gb-2013-14-1-r4 · Cited by 464 · see citing works
“Although the factors influencing the species composition and functionality of the healthy gut flora are still being revealed, food [24-26], drug uptake [14,27], inoculation at birth [28,29], host genetics [6] and as yet unknown environmental factors all seem to play a role [30].”
The role of the gut microbiota in nonalcoholic fatty liver disease
Abu-Shanab, A., & Quigley, E. M. M. (2010) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2010.172 · Cited by 457 · see citing works
From Structure to Function: the Ecology of Host-Associated Microbial Communities
Robinson, C. J., Bohannan, B. J. M., & Young, V. B. (2010) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00014-10 · Cited by 454 · see citing works
The gut microbiota and its relationship to diet and obesity
Clarke, S. F., Murphy, E. F., Nilaweera, K. N., Ross, R. P., Shanahan, F., O’Toole, P. W., & Cotter, P. D. (2012) · Gut Microbes · doi:10.4161/gmic.20168 · Cited by 458 · see citing works
“In 2009, Hildebrandt et al.(7) investigated the microbial communities from both wild-type and resistin-like molecule (RELM) β knockout (KO) mice fed a standard chow diet and a high fat diet.”
BackgroundInfluentialDiet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health
Berding, K., Vlckova, K., Marx, W., Schellekens, H., Stanton, C., Clarke, G., Jacka, F., Dinan, T. G., & Cryan, J. F. (2021) · Advances in Nutrition · doi:10.1093/advances/nmaa181 · Cited by 451 · see citing works
Etxeberria, U., Arias, N., Boqué, N., Macarulla, M. T., Portillo, M. P., Martínez, J. A., & Milagro, F. I. (2015) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2015.01.002 · Cited by 446 · see citing works
“Interestingly, concerning the enrichment found in the Bacteroidetes phylum, quercetin supplementation also deeply increased the abundance of Bacteroidaceae and Prevotellaceae families, which were stated to be negatively influenced in high-fat-fed mice [45].”
BackgroundRole of “Western Diet” in Inflammatory Autoimmune Diseases
Manzel, A., Müller, D. N., Hafler, D. A., Erdman, S. E., Linker, R. A., & Kleinewietfeld, M. (2013) · Current Allergy and Asthma Reports · doi:10.1007/s11882-013-0404-6 · Cited by 451 · see citing works
Circadian disorganization alters intestinal microbiota
Voigt, R. M., Forsyth, C. B., Green, S. J., Mutlu, E., Engen, P., Vitaterna, M. H., Turek, F. W., & Keshavarzian, A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0097500 · Cited by 439 · see citing works
“Diets high in fat tend to decrease Bacteroides and increase Firmicutes with increases in Proteobacteria also reported [22,23].”
BackgroundEarly‐life establishment of the swine gut microbiome and impact on host phenotypes
Mach, N., Berri, M., Estellé, J., Levenez, F., Lemonnier, G., Denis, C., Leplat, J. J. J. J., Chevaleyre, C., Billon, Y., Dore, J. M., et al. (2015) · Environmental Microbiology Reports · doi:10.1111/1758-2229.12285 · Cited by 446 · see citing works
Pathogenic Gut Flora in Patients With Chronic Heart Failure
Pasini, E., Aquilani, R., Testa, C., Baiardi, P., Angioletti, S., Boschi, F., Verri, M., & Dioguardi, F. S. (2015) · JACC Heart Failure · doi:10.1016/j.jchf.2015.10.009 · Cited by 440 · see citing works
“Fat intake per se and the digested fat may change the diversity of the macrobiota (20).”
Backgroundde Wit, N., Derrien, M., Bosch-Vermeulen, H., Oosterink, E., Keshtkar, S., Duval, C., de Vogel-van den Bosch, J., Kleerebezem, M., Müller, M., & van der Meer, R. (2012) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00488.2011 · Cited by 428 · see citing works
“(13) also described a lowering of bacterial sequences after consumption of a high-fat diet rich in saturated fatty acids.”
BackgroundResultThe progress of gut microbiome research related to brain disorders
Zhu, S., Jiang, Y., Xu, K., Cui, M., Ye, W., Zhao, G., Jin, L., & Chen, X. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-1705-z · Cited by 419 · see citing works
Responses of gut microbiota to diet composition and weight loss in lean and obese mice
Ravussin, Y., Koren, O., Spor, A., LeDuc, C., Gutman, R., Stombaugh, J., Knight, R., Ley, R. E., & Leibel, R. L. (2012) · Obesity · doi:10.1038/oby.2011.111 · Cited by 406 · see citing works
Self-citationLecomte, V., Kaakoush, N. O., Maloney, C., Raipuria, M., Huinao, K. D., Mitchell, H. M., & Morris, M. J. (2015) · PLoS ONE · doi:10.1371/journal.pone.0126931 · Cited by 418 · see citing works
“Furthermore, a greater proportion of Firmicutes to Bacteroidetes has been described in genetically or diet-induced obese mice [8,22,51] and rats fed a HFD [21,23,52] relative to controls.”
BackgroundInfluence of Foods and Nutrition on the Gut Microbiome and Implications for Intestinal Health
Zhang, P. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179588 · Cited by 446 · see citing works
Blautia genus associated with visceral fat accumulation in adults 20–76 years of age
Ozato, N., Saito, S., Yamaguchi, T. F., Katashima, M., Tokuda, I., Sawada, K., Katsuragi, Y., Kakuta, M., Imoto, S., Ihara, K., et al. (2019) · npj Biofilms and Microbiomes · doi:10.1038/s41522-019-0101-x · Cited by 411 · see citing works
- Authors
- Hildebrandt, M. A., Hoffmann, C., Sherrill–Mix, S. A., Keilbaugh, S. A., Hamady, M., Chen, Y., Knight, R., Ahima, R. S., Bushman, F., & Wu, G. D.
- Affiliations
- University of Pennsylvania (US)
- University of Colorado Boulder (US)
- Corresponding author
- Bushman, Frederic
- Wu, Gary D.
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2009-11
- Volume
- 137
- Issue
- 5
- Pages
- 1716-1724.e2
- ISSN
- 0016-5085 (ISSN-L)
- PMC
- PMC2770164
- OpenAlex
- W2158630697
- Cited by
- 1,576
- References
- 43
- Citations by year
- 2026: 40 · 2025: 61 · 2024: 96 · 2023: 76 · 2022: 130 · 2021: 117 · 2020: 158 · 2019: 148 · 2018: 115 · 2017: 94 · 2016: 104 · 2015: 96 · 2014: 87 · 2013: 82 · 2012: 71
- FWCI
- 22.84
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Pennsylvania
- National Institutes of Health
- National Human Genome Research Institute (R01HG004872, HG004872)
- National Institute of General Medical Sciences (T32GM065103)
- National Institute of Allergy and Infectious Diseases (R01AI039368, AI39368)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-50306, DK078669, P01DK078669, DK-019525, DK062348, R01DK062348, R56DK062348, P30DK019525, P30DK050306)
- National Center for Research Resources (S10RR024525)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- gut microbiota, high-fat diet, obesity, diet-induced obesity, Bacteroidetes, Firmicutes, Proteobacteria, gut microbiota composition, metagenomics, microbial gene content, 16S rRNA gene sequencing
- MeSH terms
- Animals, Diet, Dietary Fats, Female, Hormones, Ectopic, Intestines, Mice, Inbred C57BL, Obesity, RNA, Ribosomal, 16S, Mice, Knockout, Intercellular Signaling Peptides and Proteins, Mice, Metagenome
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