Diet and Reproducibility

Abstract  

The reproducibility of experimental data is challenged by many factors in both clinical and preclinical research. In preclinical studies, several factors may be responsible, and diet is one variable that is commonly overlooked, especially by those not trained in nutrition. In particular, grain-based diets contain complex ingredients, each of which can provide multiple nutrients, non-nutrients, and contaminants, which may vary from batch to batch. Thus, even when choosing the same grain-based diet used in the past by others, its composition will likely differ. In contrast, purified diets contain refined ingredients that offer the ability to control the composition much more closely and maintain consistency from one batch to the next, while minimizing the presence of non-nutrients and contaminants. In this article, we provide several different examples or scenarios showing how the diet choice can alter data interpretation, potentially affecting reproducibility and knowledge gained within any given field of study. Curr Dev Nutr 2020;4:nzaa031.

References

1. Smith AJ, Clutton RE, Lilley E, Hansen KEA, Brattelid T. PREPARE: guidelines for planning animal research and testing. Lab Anim 2018;52(2):135–41.
2. Pellizzon MA, Ricci MR. The common use of improper control diets in diet-induced metabolic disease research confounds data interpretation: the fiber factor. Nutr Metab (Lond) 2018;15:3.
3. Warden CH, Fisler JS. Comparisons of diets used in animal models of high-fat feeding. Cell Metab 2008;7(4):277.
4. Subcommittee on Laboratory Animal Nutrition. Committee on Animal Nutrition, Board on Agriculture, National Research Council. Nutrient requirements of laboratory animals. Washington (DC): National Academies Press; 1995.
5. Rao GN, Knapka JJ. Contaminant and nutrient concentrations of natural ingredient rat and mouse diet used in chemical toxicology studies. Fundam Appl Toxicol 1987;9(2):329–38.
6. Barnard DE, Lewis SM, Teter BB, Thigpen JE. Open- and closed-formula laboratory animal diets and their importance to research. J Am Assoc Lab Anim Sci 2009;48(6):709–13.
7. Weiskirchen S, Weiper K, Tolba RH, Weiskirchen R. All you can feed: some comments on production of mouse diets used in biomedical research with special emphasis on non-alcoholic fatty liver disease research. Nutrients 2020;12(1):163.
8. Thigpen JE, Setchell KDR, Saunders H, Haseman J, Grant M, Forsythe D. Selecting the appropriate rodent diet for endocrine disruptor research and testing studies. ILAR J 2004;45(4):401–16.
9. Thigpen JE, Setchell KD, Kissling GE, et al. The estrogenic content of rodent diets, bedding, cages, and water bottles and its effect on bisphenol A studies. J Am Assoc Lab Anim Sci 2013;52(2):130–41.
10. Jensen MN, Ritskes-Hoitinga M. How isoflavone levels in common rodent diets can interfere with the value of animal models and with experimental results. Lab Anim 2007;41(1):1–18.
11. Kozul CD, Nomikos Athena P, Hampton TH, et al. Laboratory diet profoundly alters gene expression and confounds genomic analysis in mouse liver and lung. Chem Biol Interact 2008;173(2):129–40.
12. Mesnage R, Defarge N, Rocque LM, De Vendômois JS, Séralini GE. Laboratory rodent diets contain toxic levels of environmental contaminants: implications for regulatory tests. PLoS One 2015;10(7):e0128429.
13. Waldemarson AH, Hedenqvist P, Salomonsson AC, Häggblom P. Mycotoxins in laboratory rodent feed. Lab Anim 2005;39(2):230–5.
14. Hrncir T, Stepankova R, Kozakova H, Hudcovic T, Tlaskalova-Hogenova H. Gut microbiota and lipopolysaccharide content of the diet influence development of regulatory T cells: studies in germ-free mice. BMC Immunol 2008;9:65.
15. Wise A, Gilburt DJ. The variability of dietary fiber in laboratory-animal diets and its relevance to the control of experimental conditions. Food Cosmet Toxicol 1980;18:643–8.
16. Kwiatkowski S, Thielen U, Glenney P, Moran C. A study of Saccharomyces cerevisiae cell wall glucans. J Inst Brew 2009;115(2):151–8.
17. Pellizzon MA, Ricci MR. Effects of rodent diet choice and fiber type on data interpretation of gut microbiome and metabolic disease research. Curr Protocols Toxicol 2018;77(1):e55.
18. Wise A. Interaction of diet and toxicity—the future role of purified diet in toxicological research. Arch Toxicol 1982;50(3–4):287–99.
19. Bieri J, Stoewsand G, Briggs G, Phillips R, Woodard J, Knapka JJ. Report of the American Institute of Nutrition ad hoc committee on standards for nutritional studies. J Nutr 1977;107(7):1340–8.
20. Reeves PG, Nielson FH, Fahey GC. AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition Ad Hoc Writing Committee on the reformulation of the AIN-76A rodent diet. J Nutr 1993;123:939–51.
21. Thresher JS, Podolin DA, Wei Y, Mazzeo RS, Pagliassotti MJ. Comparison of the effects of sucrose and fructose on insulin action and glucose tolerance. Am J Physiol Regul Integr Comp Physiol 2000;279(4):R1334–40.
22. Sumiyoshi M, Sakanaka M, Kimura Y. Chronic intake of high-fat and high-sucrose diets differentially affects glucose intolerance in mice. J Nutr 2006;136(3):582–7.
23. Schwarzer M, Srutkova D, Hermanova P, et al. Diet matters: endotoxin in the diet impacts the level of allergic sensitization in germ-free mice. PLoS One 2017;12(1):1–15.
24. Brown NM, Setchell KD. Animal models impacted by phytoestrogens in commercial chow: implications for pathways influenced by hormones. Lab Invest 2001;81(5):735–47.
25. Thigpen JE, Setchell KDR, Padilla-Banks E, et al. Variations in phytoestrogen content between different mill dates of the same diet produces significant differences in the time of vaginal opening in CD-1 mice and F344 rats but not in CD Sprague-Dawley rats. Environ Health Perspect 2007;115(12):1717–26.
26. Muhlhauzer A, Susiarjo M, Rubio C, et al. Bisphenol A effects on the growing mouse oocyte are influenced by diet. Biol Reprod 2009;80:1066–71.
27. Eldridge AC, Kwolek WF. Soybean isoflavones: effect of environment and variety on composition. J Agric Food Chem 1983;31(2):394–6.
28. Mead MN. The feed factor: estrogenic variability in lab animal diets. Environ Health Perspect 2006;114(11):A640–2.
29. Landete JM, Arqués J, Medina M, Gaya P, de Las Rivas BD, Muñoz R. Bioactivation of phytoestrogens: intestinal bacteria and health. Crit Rev Food Sci Nutr 2016;56(11):1826–43.
30. Thigpen JE, Haseman JK, Saunders HE, Setchell KDR, Grant MG, Forsythe DB. Dietary phytoestrogens accelerate the time of vaginal opening in immature CD-1 mice. 2003;53(6):607–15.
31. Liu B, Edgerton S, Yang X, et al. Low-dose dietary phytoestrogen abrogates tamoxifen-associated mammary tumor prevention. Cancer Res 2005;65(3):879–86.
32. Allred CD, Allred KF, Ju YH, Virant SM, Helferich WG. Soy diets containing varying amounts of genistein stimulate growth of estrogen-dependent (MCF-7) tumors in a dose-dependent manner. Cancer Res 2001;61(13):5045–50.
33. Fritz WA, Coward L, Wang J, Lamartiniere CA. Dietary genistein: perinatal mammary cancer prevention, bioavailability and toxicity testing in the rat. Carcinogenesis 1998;19(12):2151–8.
34. Ascencio C, Torres N, Isoard-Acosta F, Gómez-Pérez FJ, Hernández-Pando R, Tovar AR. Soy protein affects serum insulin and hepatic SREBP-1 mRNA and reduces fatty liver in rats. J Nutr 2004;134(3):522–9.
35. Torre-Villalvazo I, Tovar AR, Ramos-Barragán VE, Cerbón-Cervantes MA, Torres N. Soy protein ameliorates metabolic abnormalities in liver and adipose tissue of rats fed a high fat diet. J Nutr 2008;138(3):462–8.
36. Picherit C, Chanteranne B, Bennetau-Pelissero C, et al. Dose-dependent bone-sparing effects of dietary isoflavones in the ovariectomised rat. Br J Nutr 2001;85(03):307.
37. Heindel JJ, vom Saal FS. Meeting report: batch-to-batch variability in estrogenic activity in commercial animal diets—importance and approaches for laboratory animal research. Environ Health Perspect 2008;116(3):389–93.
38. Newberne PM. Influence on pharmacological experiments of chemicals and other factors in diets of laboratory animals. Food Sources Incidental Drug Expo 1975;34:209–18.
39. Greenman DL, Oller WL, Littlefield NA, Nelson CJ. Commercial laboratory animal diets: toxicant and nutrient variability. J Toxicol Environ Health 1980;6:235–46.
40. National Research Council. Arsenic in drinking water. Washington (DC): National Academies Press; 1999.
41. National Research Council. Arsenic in drinking water: 2001 update. Washington (DC): National Academies Press; 2001.
42. Kozul CD, Hampton TH, Davey JC, et al. Chronic exposure to arsenic in the drinking water alters the expression of immune response genes in mouse lung. Environ Health Perspect 2009;117(7):1108–15.
43. Kozul CD, Ely KH, Enellow RI, Hamilton JW. Low-dose arsenic compromises the immune response to influenza A infection in vivo. Environ Health Perspect 2009;117(9):1441–7.
44. Castriota F, Zushin P-JH, Sanchez SS, et al. Chronic arsenic exposure impairs adaptive thermogenesis in male C57BL/6 J mice. Am J Physiol Metab 2020; doi:10.1152/ajpendo.00282.
45. Alshannaq A, Yu JH. Occurrence, toxicity, and analysis of major mycotoxins in food. Int J Environ Res Public Health 2017;14(6):632.
46. Whitlow L, Hagler W, Diaz D. Mycotoxins in feeds. Feedstuffs 2010;74–84.
47. Yiannikouris A, Jouany J-P. Mycotoxins in feeds and their fate in animals: a review. Anim Res 2002;51:81–99.
48. Kouadio JH, Dano SD, Moukha S, Mobio TA, Creppy EE. Effects of combinations of Fusarium mycotoxins on the inhibition of macromolecular synthesis, malondialdehyde levels, DNA methylation and fragmentation, and viability in Caco-2 cells. Toxicon 2007;49(3):306–17.
49. Porter JK, Wray EM, Rimando AM, Stance PC, Bacon CW, Voss KA. Lactational passage of fusaric acid from the feed of nursing dams to the neonate rat and effects on pineal neurochemistry in the F1 and F2 generations at weaning. J Toxicol Environ Health 1996;49(2):161–75.
50. Underhill KL, Rotter BA, Thompson BK, Prelusky DB, Trenholm HL. Effectiveness of cholestyramine in the detoxification of zearalenone as determined in mice. Bull Environ Contam Toxicol 1995;54(1):128–34.
51. Yakar S, Nunez NP, Pennisi P, et al. Increased tumor growth in mice with diet-induced obesity: impact of ovarian hormones. Endocrinology 2006;147(12):5826–34.
52. Kilcast D. Effect of irradiation on vitamins. Food Chem 1994;49:157–64.
53. Caulfield CD, Cassidy JP, Kelly JP. Effects of gamma irradiation and pasteurization on the nutritive composition of commercially available animal diets. J Am Assoc Lab Anim Sci 2008;47(6):61–6.
54. Cebra JJ. Influences of microbiota on intestinal immune system. Am J Clin Nutr 1999;69(Suppl):1046S.
55. Dollive S, Chen Y, Grunberg S, et al. Fungi of the murine gut: episodic variation and proliferation during antibiotic treatment. PLoS One 2013;8(8):e71806.
56. Irvin A, Cockburn A, Primerano DA, et al. Diet-induced alteration of the murine intestinal microbiome following antibiotic ablation. Biomed Life Sci 2017;7(7):545–64.
57. Shukla Y, Arora A, Singh A. Tumourigenic studies on deltamethrin in Swiss albino mice. Toxicology 2001;163(1):1–9.
58. Rodriguez-Vivas RI, Li AY, Ojeda-Chi MM, et al. In vitro and in vivo evaluation of cypermethrin, amitraz, and piperonyl butoxide mixtures for the control of resistant Rhipicephalus (Boophilus) microplus (Acari: Ixodidae) in the Mexican tropics. Vet Parasitol 2013;197(1–2):288–96.
59. George J, Prasad S, Mahmood Z, Shukla Y. Studies on glyphosate-induced carcinogenicity in mouse skin: a proteomic approach. J Proteomics 2010;73(5):951–64.
60. Séralini GE, Clair E, Mesnage R, et al. Republished study: long-term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize. Environ Sci Eur 2014;26(1):1–17.
61. Schecter AJ, Olson J, Papke O. Exposure of laboratory animals to polychlorinated dibenzodioxins and polychlorinated dibenzofurans from commercial rodent chow. Chemosphere 1996;32(3):501–8.
62. Zhang L, Nichols RG, Patterson AD. The aryl hydrocarbon receptor as a moderator of host-microbiota communication. Curr Opin Toxicol 2017;2:30–5.
63. Ito S, Chen C, Satoh J, Yim S, Gonzalez FJ. Dietary phytochemicals regulate whole-body CYP1A1 expression through an arylhydrocarbon receptor nuclear translocator-dependent system in gut. J Clin Invest 2007;117(7):1940–50.
64. Li Y, Innocentin S, Withers DR, et al. Exogenous stimuli maintain intraepithelial lymphocytes via aryl hydrocarbon receptor activation. Cell 2011;147(3):629–40.
65. Stevenson L, Phillips F, O'Sullivan K, Walton J. Wheat bran: its composition and benefits to health, a European perspective. Int J Food Sci Nutr 2012;63(8):1001–13.
66. Vitaglione P, Napolitano A, Fogliano V. Cereal dietary fibre: a natural functional ingredient to deliver phenolic compounds into the gut. Trends Food Sci Technol 2008;19(9):451–63.
67. den Besten G, van Eunen K, Groen AK, Venema K, Reijngoud D-J, Bakker BM. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res 2013;54(9):2325–40.
68. Ericsson AC, Gagliardi J, Bouhan D, Spollen WG, Givan SA, Franklin CL. The influence of caging, bedding, and diet on the composition of the microbiota in different regions of the mouse gut. Sci Rep 2018;8(1):1–13.
69. Jovel J, Patterson J, Wang W, et al. Characterization of the gut microbiome using 16S or shotgun metagenomics. Front Microbiol 2016;7:1–17.
70. Dalby MJ, Ross AW, Walker AW, Morgan PJ. Dietary uncoupling of gut microbiota and energy harvesting from obesity and glucose tolerance in mice. Cell Rep 2017;21:1521–33.
71. Chassaing B, Miles-Brown J, Pellizzon M, et al. Lack of soluble fiber drives diet-induced adiposity in mice. Am J Physiol Gastrointest Liver Physiol 2015;309:G528–41.
72. Hwang IS, Ho H, Hoffman BB, Reaven GM. Fructose-induced insulin resistance and hypertension in rats. Hypertension 1987;10(5):512–6.
73. Pagliassotti MJ, Prach PA. Quantity of sucrose alters the tissue pattern and time course of insulin resistance in young rats. Am J Physiol 1995;269(3 Pt 2):R641–6.
74. Pagliassotti MJ, Prach PA, Koppenhafer TA, Pan DA. Changes in insulin action, triglycerides, and lipid composition during sucrose feeding in rats. Am J Physiol 1996;271(5 Pt 2):R1319–26.
75. Mattson DL, Kunert MP, Kaldunski ML, et al. Influence of diet and genetics on hypertension and renal disease in Dahl salt-sensitive rats. Physiol Genomics 2004;16(2):194–203.
76. Fullerton FR, Greenman DL, Bucci TJ. Effects of diet type on incidence of spontaneous and acetylaminofluorene-induced liver and bladder tumors in Balb/c mice fed AIN-76A versus NIH-07 diet. Fundam Appl Toxicol 1992;18:193–9.
77. Lien EL, Boyle FG, Wrenn JM, Perry RW, Thompson CA, Borzelleca JF. Comparison of AIN-76A and AIN-93G diets: a 13-week study in rats. Food Chem Toxicol 2001;39(4):385–92.
78. Reeves PG, Rossow KL, Lindlauf J. Development and testing of the AIN-93 purified diets for rodents: results on growth, kidney calcification and bone mineralization in rats and mice. J Nutr 1993;123:1923–31.
79. Delzenne NM, Daubioul C, Neyrinck A, Lasa MTH. Inulin and oligofructose modulate lipid metabolism in animals: review of biochemical events and future prospects. Br J Nutr 2002;87(Suppl 2):S255–9.
80. Delzenne NM, Cani PD, Neyrinck AM. Modulation of glucagon-like peptide 1 and energy metabolism by inulin and oligofructose: experimental data. J Nutr 2007;137(11 Suppl):2547S–51S.
81. Zou J, Chassaing B, Singh V, et al. Fiber-mediated nourishment of gut microbiota protects against diet-induced obesity by restoring IL-22-mediated colonic health. Cell Host Microbe 2018;23:1–13.
82. Chassaing B, Vijay-Kumar M, Gewirtz AT. How diet can impact gut microbiota to promote or endanger health. Curr Opin Gastroenterol 2017;33(6):417–21.