Substituting whole grains for refined grains in a 6-wk randomized trial has a modest effect on gut microbiota and immune and inflammatory markers of healthy adults

American Journal of Clinical Nutrition

Volumn 105, Issue 3, 2017, Pages 635-650

  Vanegas, Sally M ^a,b   Meydani, Mohsen ^a   Barnett, Junaidah B ^a   Goldin, Barry ^b,c   Kane, Anne ^c   Rasmussen, Helen ^a   Brown, Carrie ^a,g   Vangay, Pajau ^d   Knights, Dan ^e   Jonnalagadda, Satya ^f,h   Koecher, Katie ^f   Philip Karl, J ^a,i   Thomas, Michael ^a   Dolnikowski, Gregory ^a   Li, Lijun ^a   Saltzman, Edward ^a,b   Wu, Dayong ^a   Meydani, Simin Nikbin ^a  

^a TUFTS UNIVERSITY   (United States)

^b TUFTS UNIVERSITY   (United States)

^c TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d UNIVERSITY OF MARYLAND   (United States)

^e University of Minnesota   (United States)

^f GENERAL MILLS INC   (United States)

^g BOSTON UNIVERSITY SCHOOL OF PUBLIC HEALTH   (United States)

^h Kerry Ingredients and Flavours   (United States)

ⁱ U S ARMY RESEARCH INSTITUTE OF ENVIRONMENTAL MEDICINE   (United States)

Author keywords

Gut microbiota; Healthy adults; Immune; Inflammation; Whole grains

Indexed keywords

ACETIC ACID; ALKYRESORCINOLS; BUTYRIC ACID; CHOLESTEROL; FOLIC ACID; IRON; LIPID; LIPOPOLYSACCHARIDE; MAGNESIUM; NICOTINIC ACID; SELENIUM; SHORT CHAIN FATTY ACID; THIAMINE; TRACE ELEMENT; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG; VITAMIN D; ZINC; BIOLOGICAL MARKER; BUTYRIC ACID DERIVATIVE; RESORCINOL DERIVATIVE;

ADULT; AGED; ARTICLE; BODY WEIGHT; CHOLESTEROL BLOOD LEVEL; CONTROLLED STUDY; CYTOKINE PRODUCTION; DIETARY FIBER; DIGESTIVE TRACT PARAMETERS; ENTEROBACTERIACEAE; EX VIVO STUDY; FECES MICROFLORA; FEMALE; HUMAN; HUMAN CELL; INTESTINE FLORA; INTESTINE MOTILITY; LACHNOSPIRACEAE; MACRONUTRIENT; MALE; MEMORY T LYMPHOCYTE; MINERAL INTAKE; NORMAL HUMAN; REFINED GRAIN; ROSEBURIA; STOOL FREQUENCY; STOOL WEIGHT; VITAMIN INTAKE; WESTERN DIET; WHOLE GRAIN; BACTERIUM; BLOOD; BODY WEIGHT MAINTENANCE; COMPARATIVE STUDY; DEFECATION; DIET; FECES; FEEDING BEHAVIOR; GASTROINTESTINAL TRACT; GROWTH, DEVELOPMENT AND AGING; IMMUNOLOGY; INFLAMMATION; INNATE IMMUNITY; METABOLISM; MICROBIOLOGY; MIDDLE AGED; PHARMACOLOGY; RANDOMIZED CONTROLLED TRIAL; T LYMPHOCYTE;

ACETIC ACID; AGED; BACTERIA; BIOMARKERS; BODY WEIGHT MAINTENANCE; BUTYRATES; DEFECATION; DIET; DIETARY FIBER; ENTEROBACTERIACEAE; FECES; FEEDING BEHAVIOR; FEMALE; GASTROINTESTINAL MICROBIOME; GASTROINTESTINAL TRACT; HUMANS; IMMUNITY, INNATE; INFLAMMATION; LIPOPOLYSACCHARIDES; MALE; MIDDLE AGED; RESORCINOLS; T-LYMPHOCYTES; TUMOR NECROSIS FACTOR-ALPHA; WHOLE GRAINS;

EID: 85020291843     PISSN: 00029165     EISSN: 19383207     Source Type: Journal    
DOI: 10.3945/ajcn.116.146928     Document Type: Article

References (71)

1. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin re-sistance. Science 1993;259:87-91.
2. Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J Clin Invest 2005;115:1111-9.
3. Egger G. In search of a germ theory equivalent for chronic disease. Prev Chronic Dis 2012;9:E95.
4. Jacobs DR Jr., Meyer HE, Solvoll K. Reduced mortality among whole grain bread eaters in men and women in the Norwegian County Study. Eur J Clin Nutr 2001;55:137-43.
5. Jensen MK, Koh-Banerjee P, Franz M, Sampson L, Gronbaek M, Rimm EB. Whole grains, bran, and germ in relation to homocysteine and markers of glycemic control, lipids, and inflammation 1. Am J Clin Nutr 2006;83:275-83.
6. Jacobs DR Jr., Andersen LF, Blomhoff R. Whole-grain consumption is associated with a reduced risk of noncardiovascular, noncancer death attributed to inflammatory diseases in the Iowa Women's Health Study. Am J Clin Nutr 2007;85:1606-14.
7. Hamer DH, Sempertegui F, Estrella B, Tucker KL, Rodriguez A, Egas J, Dallal GE, Selhub J, Griffiths JK, Meydani SN. Micronutrient deficiencies are associated with impaired immune response and higher burden of respiratory infections in elderly Ecuadorians. J Nutr 2009; 139:113-9.
8. Nettleton JA, Schulze MB, Jiang R, Jenny NS, Burke GL, Jacobs DR Jr. A priori-defined dietary patterns and markers of cardiovascular disease risk in the Multi-Ethnic Study of Atherosclerosis (MESA). Am J Clin Nutr 2008;88:185-94.
9. Sun Q, Spiegelman D, van Dam RM, Holmes MD, Malik VS, Willett WC, Hu FB. White rice, brown rice, and risk of type 2 diabetes in US men and women. Arch Intern Med 2010;170:961-9.
10. Slavin J, Jacobs D, Marquart L. Whole-grain consumption and chronic disease: protective mechanisms. Nutr Cancer 1997;27:14-21.
11. Adom KK, Sorrells ME, Liu RH. Phytochemicals and antioxidant activity of milled fractions of different wheat varieties. J Agric Food Chem 2005;53:2297-306.
12. Fardet A. New hypotheses for the health-protective mechanisms of whole-grain cereals: what is beyond fibre? Nutr Res Rev 2010;23:65-134.
13. De Filippo C, Cavalieri D, Di Paola M, Ramazzotti M, Poullet JB, Massart S, Collini S, Pieraccini G, Lionetti P. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci USA 2010;107:14691-6.
14. Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, Bewtra M, Knights D, Walters WA, Knight R, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science 2011;334: 105-8.
15. Ou J, Carbonero F, Zoetendal EG, DeLany JP, Wang M, Newton K, Gaskins HR, O'Keefe SJ. Diet, microbiota, and microbial metabolites in colon cancer risk in rural Africans and African Americans. Am J Clin Nutr 2013;98:111-20.
16. Benus RF, van der Werf TS, Welling GW, Judd PA, Taylor MA, Harmsen HJ, Whelan K. Association between Faecalibacterium prausnitzii and dietary fibre in colonic fermentation in healthy human subjects. Br J Nutr 2010;104:693-700.
17. Bengmark S. Gut microbiota, immune development and function. Pharmacol Res 2013;69:87-113.
18. Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T, Karaoz U, Wei D, Goldfarb KC, Santee CA, Lynch SV, et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 2009;139: 485-98.
19. Ivanov II, Frutos Rde L, Manel N, Yoshinaga K, Rifkin DB, Sartor RB, Finlay BB, Littman DR. Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe 2008;4:337-49.
20. Ostman S, Rask C, Wold AE, Hultkrantz S, Telemo E. Impaired regulatory T cell function in germ-free mice. Eur J Immunol 2006;36: 2336-46.
21. Segain JP, Raingeard de la Bletiere D, Bourreille A, Leray V, Gervois N, Rosales C, Ferrier L, Bonnet C, Blottiere HM, Galmiche JP. Butyrate inhibits inflammatory responses through NFkappaB inhibition: implications for Crohn's disease. Gut 2000;47:397-403.
22. Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F, Yu D, Schilter HC, Rolph MS, Mackay F, Artis D, et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 2009;461:1282-6.
23. Qi L, van Dam RM, Liu S, Franz M, Mantzoros C, Hu FB. Whole-grain, bran, and cereal fiber intakes and markers of systemic inflammation in diabetic women. Diabetes Care 2006;29:207-11.
24. Gaskins AJ, Mumford SL, Rovner AJ, Zhang C, Chen L, Wactawski-Wende J, Perkins NJ, Schisterman EF. Whole grains are associated with serum concentrations of high sensitivity C-reactive protein among premenopausal women. J Nutr 2010;140:1669-76.
25. Masters RC, Liese AD, Haffner SM, Wagenknecht LE, Hanley AJ. Whole and refined grain intakes are related to inflammatory protein concentrations in human plasma. J Nutr 2010;140:587-94.
26. Montonen J, Boeing H, Fritsche A, Schleicher E, Joost HG, Schulze MB, Steffen A, Pischon T. Consumption of red meat and whole-grain bread in relation to biomarkers of obesity, inflammation, glucose metabolism and oxidative stress. Eur J Nutr 2013;52:337-45.
27. Jensen MK, Koh-Banerjee P, Hu FB, Franz M, Sampson L, Gronbaek M, Rimm EB. Intakes of whole grains, bran, and germ and the risk of coronary heart disease in men. Am J Clin Nutr 2004;80:1492-9.
28. Lutsey PL, Jacobs DR Jr., Kori S, Mayer-Davis E, Shea S, Steffen LM, Szklo M, Tracy R. Whole grain intake and its cross-sectional associ-ation with obesity, insulin resistance, inflammation, diabetes and sub-clinical CVD: the MESA Study. Br J Nutr 2007;98:397-405.
29. Sofi F, Ghiselli L, Cesari F, Gori AM, Mannini L, Casini A, Vazzana C, Vecchio V, Gensini GF, Abbate R, et al. Effects of short-term consumption of bread obtained by an old Italian grain variety on lipid, inflammatory, and hemorheological variables: an intervention study. J Med Food 2010;13:615-20.
30. Martinez I, Lattimer JM, Hubach KL, Case JA, Yang J, Weber CG, Louk JA, Rose DJ, Kyureghian G, Peterson DA, et al. Gut microbiome composition is linked to whole grain-induced immunological im-provements. ISME J 2013;7:269-80.
31. Vitaglione P, Mennella I, Ferracane R, Rivellese AA, Giacco R, Ercolini D, Gibbons SM, La Storia A, Gilbert JA, Jonnalagadda S, et al. Whole-grain wheat consumption reduces inflammation in a randomized controlled trial on overweight and obese subjects with unhealthy dietary and lifestyle behaviors: role of polyphenols bound to cereal dietary fiber. Am J Clin Nutr 2015;101:251-61.
32. Andersson A, Tengblad S, Karlstrom B, Kamal-Eldin A, Landberg R, Basu S, Aman P, Vessby B. Whole-grain foods do not affect insulin sensitivity or markers of lipid peroxidation and inflammation in healthy, moderately overweight subjects. J Nutr 2007;137:1401-7.
33. Tighe P, Duthie G, Vaughan N, Brittenden J, Simpson WG, Duthie S, Mutch W, Wahle K, Horgan G, Thies F. Effect of increased consumption of whole-grain foods on blood pressure and other cardiovascular risk markers in healthy middle-aged persons: a randomized controlled trial. Am J Clin Nutr 2010;92:733-40.
34. Brownlee IA, Moore C, Chatfield M, Richardson DP, Ashby P, Kuznesof SA, Jebb SA, Seal CJ. Markers of cardiovascular risk are not changed by increased whole-grain intake: the WHOLEheart study, a randomised, controlled dietary intervention. Br J Nutr 2010;104:125-34.
35. Ampatzoglou A, Williams CL, Atwal KK, Maidens CM, Ross AB, Thielecke F, Jonnalagadda SS, Kennedy OB, Yaqoob P. Effects of increased wholegrain consumption on immune and inflammatory markers in healthy low habitual wholegrain consumers. Eur J Nutr 2016;55:183-95.
36. Meydani SN, Meydani M, Blumberg JB, Leka LS, Siber G, Loszewski R, Thompson C, Pedrosa MC, Diamond RD, Stollar BD. Vitamin E supplementation and in vivo immune response in healthy elderly subjects. A randomized controlled trial. JAMA 1997;277: 1380-6.
37. Cossack ZT. T-lymphocyte dysfunction in the elderly associated with zinc deficiency and subnormal nucleoside phosphorylase activity: effect of zinc supplementation. Eur J Cancer Clin Oncol 1989;25:973-6.
38. Vulevic J, Drakoularakou A, Yaqoob P, Tzortzis G, Gibson GR. Modulation of the fecal microflora profile and immune function by a novel trans-galactooligosaccharide mixture (B-GOS) in healthy elderly volunteers. Am J Clin Nutr 2008;88:1438-46.
39. US Department of Agriculture, US Department of Health and Human Services. Dietary Guidelines for Americans, 2010. 7th ed. Washington (DC): US Government Posting Office; 2010.
40. McKeown NM, Marklund M, Ma J, Ross AB, Lichtenstein AH, Livingston KA, Jacques PF, Rasmussen HM, Blumberg JB, Chen CY. Comparison of plasma alkylresorcinols (AR) and urinary AR metabolites as biomarkers of compliance in a short-term, whole-grain intervention study. Eur J Nutr 2016;55:1235-44.
41. Miletic ID, Schiffman SS, Miletic VD, Sattely-Miller EA. Salivary IgA secretion rate in young and elderly persons. Physiol Behav 1996;60: 243-8.
42. Caporaso JG, Lauber CL, Walters WA, Berg-Lyons D, Huntley J, Fierer N, Owens SM, Betley J, Fraser L, Bauer M, et al. Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms. ISME J 2012;6:1621-4.
43. Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, Fierer N, Pena AG, Goodrich JK, Gordon JI, et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods 2010;7:335-6.
44. McDonald D, Price MN, Goodrich J, Nawrocki EP, DeSantis TZ, Probst A, Andersen GL, Knight R, Hugenholtz P. An improved Greengenes taxonomy with explicit ranks for ecological and evolutionary analyses of bacteria and archaea. ISME J 2012;6: 610-8.
45. Edgar RC. Search and clustering orders of magnitude faster than BLAST. Bioinformatics 2010;26:2460-1.
46. Lozupone C, Lladser ME, Knights D, Stombaugh J, Knight R. UniFrac: an effective distance metric for microbial community comparison. ISME J 2011;5:169-72.
47. Tomcik K, Ibarra RA, Sadhukhan S, Han Y, Tochtrop GP, Zhang GF. Isotopomer enrichment assay for very short chain fatty acids and its metabolic applications. Anal Biochem 2011;410:110-7.
48. Zhao G, Nyman M, Jonsson JA. Rapid determination of short-chain fatty acids in colonic contents and faeces of humans and rats by acidified water-extraction and direct-injection gas chromatography. Biomed Chromatogr 2006;20:674-82.
49. Saraji M, Farajmand B. Application of single-drop microextraction combined with in-microvial derivatization for determination of acidic herbicides in water samples by gas chromatography-mass spectrometry. J Chromatogr A 2008;1178:17-23.
50. Nicholls S, Stephens S, Braegger CP, Walker-Smith JA, MacDonald TT. Cytokines in stools of children with inflammatory bowel disease or in-fective diarrhoea. J Clin Pathol 1993;46:757-60.
51. Davis C, Wu X, Li W, Fan H, Reddy M. Stability of im-munophenotypic markers in fixed peripheral blood for extended analysis using flow cytometry. J Immunol Methods 2011;363:158-65.
52. Marklund M, McKeown NM, Blumberg JB, Chen CY. Hepatic bio-transformation of alkylresorcinols is mediated via cytochrome P450 and beta-oxidation: a proof of concept study. Food Chem 2013;139: 925-30.
53. Hornung V, Guenthner-Biller M, Bourquin C, Ablasser A, Schlee M, Uematsu S, Noronha A, Manoharan M, Akira S, de Fougerolles A, et al. Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7. Nat Med 2005;11:263-70.
54. Cassidy A, Rogers G, Peterson JJ, Dwyer JT, Lin H, Jacques PF. Higher dietary anthocyanin and flavonol intakes are associated with anti-inflammatory effects in a population of US adults. Am J Clin Nutr 2015;102:172-81.
55. Bloemena E, Roos MT, Van Heijst JL, Vossen JM, Schellekens PT. Whole-blood lymphocyte cultures. J Immunol Methods 1989;122: 161-7.
56. De Groote D, Zangerle PF, Gevaert Y, Fassotte MF, Beguin Y, Noizat-Pirenne F, Pirenne J, Gathy R, Lopez M, Dehart I, et al. Direct stim-ulation of cytokines (IL-1 beta, TNF-alpha, IL-6, IL-2, IFN-gamma and GM-CSF) in whole blood. I. Comparison with isolated PBMC stimulation. Cytokine 1992;4:239-48.
57. Hornung RW, Reed LD. Estimation of average concentration in the presence of nondetectable values. Appl Occup Environ Hyg 1990;5: 46-51.
58. Kim GG, Donnenberg VS, Donnenberg AD, Gooding W, Whiteside TL. A novel multiparametric flow cytometry-based cytotoxicity assay simultaneously immunophenotypes effector cells: comparisons to a 4 h 51Cr-release assay. J Immunol Methods 2007;325:51-66.
59. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502.
60. Hornik K. The comprehensive R archive network. WIREs Comp Stat 2012;4:394-8.
61. Ross AB, Shepherd MJ, Schupphaus M, Sinclair V, Alfaro B, Kamal-Eldin A, Aman P. Alkylresorcinols in cereals and cereal products. J Agric Food Chem 2003;51:4111-8.
62. Ross AB, Kamal-Eldin A, Lundin EA, Zhang JX, Hallmans G, Aman P. Cereal alkylresorcinols are absorbed by humans. J Nutr 2003; 133:2222-4.
63. Wrick KL, Robertson JB, Van Soest PJ, Lewis BA, Rivers JM, Roe DA, Hackler LR. The influence of dietary fiber source on human intestinal transit and stool output. J Nutr 1983;113:1464-79.
64. Anand P, Kunnumakkara AB, Sundaram C, Harikumar KB, Tharakan ST, Lai OS, Sung B, Aggarwal BB. Cancer is a preventable disease that requires major lifestyle changes. Pharm Res 2008;25:2097-116.
65. Vomero ND, Colpo E. Nutritional care in peptic ulcer. Arq Bras Cir Dig 2014;27:298-302.
66. Kristensen M, Toubro S, Jensen MG, Ross AB, Riboldi G, Petronio M, Bugel S, Tetens I, Astrup A. Whole grain compared with refined wheat decreases the percentage of body fat following a 12-week, energy-restricted dietary intervention in postmenopausal women. J Nutr 2012;142:710-6.
67. Ampatzoglou A, Atwal KK, Maidens CM, Williams CL, Ross AB, Thielecke F, Jonnalagadda SS, Kennedy OB, Yaqoob P. Increased whole grain consumption does not affect blood biochemistry, body composition, or gut microbiology in healthy, low-habitual whole grain consumers. J Nutr 2015;145:215-21.
68. Topping DL, Clifton PM. Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol Rev 2001;81:1031-64.
69. Louis P, Scott KP, Duncan SH, Flint HJ. Understanding the effects of diet on bacterial metabolism in the large intestine. J Appl Microbiol 2007;102:1197-208.
70. Lu ZX, Gibson PR, Muir JG, Fielding M, O'Dea K. Arabinoxylan fiber from a by-product of wheat flour processing behaves physiologically like a soluble, fermentable fiber in the large bowel of rats. J Nutr 2000;130:1984-90.
71. Davy BM, Davy KP, Ho RC, Beske SD, Davrath LR, Melby CL. High-fiber oat cereal compared with wheat cereal consumption favorably alters LDL-cholesterol subclass and particle numbers in middle-aged and older men. Am J Clin Nutr 2002;76:351-8.