Walnut Consumption Alters the Gastrointestinal Microbiota, Microbially Derived Secondary Bile Acids, and Health Markers in Healthy Adults: A Randomized Controlled Trial

Hannah D Holscher, Heather M Guetterman, Kelly S Swanson, Ruopeng An, Nirupa R Matthan, Alice H Lichtenstein, Janet A Novotny, David J Baer, Hannah D Holscher, Heather M Guetterman, Kelly S Swanson, Ruopeng An, Nirupa R Matthan, Alice H Lichtenstein, Janet A Novotny, David J Baer

Abstract

Background: Epidemiologic data suggest that diets rich in nuts have beneficial health effects, including reducing total and cause-specific mortality from cancer and heart disease. Although there is accumulating preclinical evidence that walnuts beneficially affect the gastrointestinal microbiota and gut and metabolic health, these relations have not been investigated in humans.

Objective: We aimed to assess the impact of walnut consumption on the human gastrointestinal microbiota and metabolic markers of health.

Methods: A controlled-feeding, randomized crossover study was undertaken in healthy men and women [n = 18; mean age = 53.1 y; body mass index (kg/m2): 28.8]. Study participants received isocaloric diets containing 0 or 42 g walnuts/d for two 3-wk periods, with a 1-wk washout between diet periods. Fecal and blood samples were collected at baseline and at the end of each period to assess secondary outcomes of the study, including effects of walnut consumption on fecal microbiota and bile acids and metabolic markers of health.

Results: Compared with after the control period, walnut consumption resulted in a 49-160% higher relative abundance of Faecalibacterium, Clostridium, Dialister, and Roseburia and 16-38% lower relative abundances of Ruminococcus, Dorea, Oscillospira, and Bifidobacterium (P < 0.05). Fecal secondary bile acids, deoxycholic acid and lithocholic acid, were 25% and 45% lower, respectively, after the walnut treatment compared with the control treatment (P < 0.05). Serum LDL cholesterol and the noncholesterol sterol campesterol concentrations were 7% and 6% lower, respectively, after walnut consumption compared with after the control treatment (P < 0.01).

Conclusion: Walnut consumption affected the composition and function of the human gastrointestinal microbiota, increasing the relative abundances of Firmicutes species in butyrate-producing Clostridium clusters XIVa and IV, including Faecalibacterium and Roseburia, and reducing microbially derived, proinflammatory secondary bile acids and LDL cholesterol. These results suggest that the gastrointestinal microbiota may contribute to the underlying mechanisms of the beneficial health effects of walnut consumption. This trial was registered at www.clinicaltrials.gov as NCT01832909.

Figures

FIGURE 1
FIGURE 1
Bivariate correlations between fecal Dorea (A) and Roseburia (B) sequence abundances and lithocholic acid concentrations at the end of the walnut treatment period.

References

    1. Sender R, Fuchs S, Milo R. Are we really vastly outnumbered? Revisiting the ratio of bacterial to host cells in humans. Cell 2016;164:337–40.
    1. Qin J, Li Y, Cai Z, Li S, Zhu J, Zhang F, Liang S, Zhang W, Guan Y, Shen D. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 2012;490:55–60.
    1. Ley RE, Bäckhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI, Backhed F, Turnbaugh P, Lozupone CA, Knight RD, et al.Obesity alters gut microbial ecology. Proc Natl Acad Sci USA 2005;102:11070–5.
    1. Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, DuGar B, Feldstein AE, Britt EB, Fu X, Chung Y-M, et al.Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 2011;472:57–63.
    1. Fu J, Bonder MJ, Cenit MC, Tigchelaar EF, Maatman A, Dekens JA, Brandsma E, Marczynska J, Imhann F, Weersma RK, et al.The gut microbiome contributes to a substantial proportion of the variation in blood lipids. Circ Res 2015;117:817–24.
    1. Karlsson FH, Fåk F, Nookaew I, Tremaroli V, Fagerberg B, Petranovic D, Bäckhed F, Nielsen J. Symptomatic atherosclerosis is associated with an altered gut metagenome. Nat Commun 2012;3:1245.
    1. Bao Y, Han J, Hu FB, Giovannucci EL, Stampfer MJ, Willett WC, Fuchs CS. Association of nut consumption with total and cause-specific mortality. N Engl J Med 2013;369:2001–11.
    1. Wu GD, Chen J, Hoffmann C, Bittinger K, Chen Y, 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.
    1. David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, Ling AV, Devlin AS, Varma Y, Fischbach MA, et al.Diet rapidly and reproducibly alters the human gut microbiome. Nature 2013;505:559–63.
    1. Holscher HD, Caporaso JG, Hooda S, Brulc JM, Fahey GCJ, Swanson KS, Fahey GC Jr., Swanson KS. Fiber supplementation influences phylogenetic structure and functional capacity of the human intestinal microbiome: follow-up of a randomized controlled trial. Am J Clin Nutr 2015;101:55–64.
    1. Holscher HD, Bauer LL, Vishnupriya G, Pelkman CL, Fahey GC, Swanson KS, Gourineni V, Pelkman CL, Fahey GC Jr., Swanson KS. Agave inulin supplementation affects the fecal microbiota of healthy adults participating in a randomized, double-blind, placebo-controlled, crossover trial. J Nutr 2015;145:2025–32.
    1. Holscher HD. Dietary fiber and prebiotics and the gastrointestinal microbiota. Gut Microbes 2017;8:172–84.
    1. Baer DJ, Gebauer SK, Novotny JA. Walnuts consumed by healthy adults provide less available energy than predicted by the Atwater factors. J Nutr 2015;9–13.
    1. Matthan NR. Impact of simvastatin, niacin, and/or antioxidants on cholesterol metabolism in CAD patients with low HDL. J Lipid Res 2003;44:800–6.
    1. Matthan NR, Pencina M, LaRocque JM, Jacques PF, D'Agostino RB, Schaefer EJ, Lichtenstein AH. Alterations in cholesterol absorption/synthesis markers characterize Framingham Offspring Study participants with CHD. J Lipid Res 2009;50:1927–35.
    1. 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.
    1. Schoch CL, Seifert KA, Huhndorf S, Robert V, Spouge JL, Levesque CA, Chen W, et al. ; Fungal Barcoding Consortium . Nuclear ribosomal internal transcribed spacer (ITS) region as a universal DNA barcode marker for Fungi. Proc Natl Acad Sci USA 2012;109:1–6.
    1. Venable EB, Fenton KA, Braner VM, Reddington CE, Halpin MJ, Heitz SA, Francis JM, Gulson NA, Goyer CL, Bland SD, et al.Effects of feeding management on the equine cecal microbiota. J Equine Vet Sci 2017;49:113–21.
    1. Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, Fierer N, Peña AG, Goodrich JK, Gordon JI, et al.QIIME allows analysis of high-throughput community sequencing data. Nature 2010;7:335–6.
    1. Bokulich NA, Subramanian S, Faith JJ, Gevers D, Gordon JI, Knight R, Mills DA, Caporaso JG. Quality-filtering vastly improves diversity estimates from Illumina amplicon sequencing. Nat Methods 2013;10:57–9.
    1. Langille MGI, Zaneveld J, Caporaso JG, McDonald D, Knights D, Reyes JA, Clemente JC, Burkepile DE, Thurber RLV, Knight R. Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nat Biotechnol 2013;31:814–21.
    1. Folch J, Lees M, Stanley GHS. A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 1957;226:497–509.
    1. Nakanishi M, Chen Y, Qendro V, Miyamoto S, Weinstock E, Weinstock GM, Rosenberg DW. Effects of walnut consumption on colon carcinogenesis and microbial community structure. Cancer Prev Res 2016;9:692–703.
    1. Byerley LO, Samuelson D, Blanchard E, Luo M, Lorenzen BN, Banks S, Ponder MA, Welsh DA, Taylor CM. Changes in the gut microbial communities following addition of walnuts to the diet. J Nutr Biochem 2017;48:94–102.
    1. Pryde SE, Duncan SH, Hold GL, Stewart CS, Flint HJ. The microbiology of butyrate formation in the human colon. FEMS microbiology letters 2002;217:133–9.
    1. Duncan SH, Hold GL, Barcenilla A, Stewart CS, Flint HJ. Roseburia intestinalis sp. nov., a novel saccharolytic, butyrate-producing bacterium from human faeces. Int J Syst Evol Microbiol 2002;52:1615–20.
    1. Duncan SH, Hold GL, Harmsen HJ, Stewart CS, Flint HJ. Growth requirements and fermentation products of Fusobacterium prausnitzii, and a proposal to reclassify it as Faecalibacterium prausnitzii gen. nov., comb. nov. Int J Syst Evol Microbiol 2002;52:2141–6.
    1. Mandalari G, Nueno-Palop C, Bisignano G, Wickham MSJ, Narbad A. Potential prebiotic properties of almond (Amygdalus communis L.) seeds. Appl Environ Microbiol 2008;74:4264–70.
    1. Ridlon JM. Bile salt biotransformations by human intestinal bacteria. J Lipid Res 2005;47:241–59.
    1. Ochsenkühn T, Bayerdörffer E, Meining A, Schinkel M, Thiede C, Nüssler V, Sackmann M, Hatz R, Neubauer A, Paumgartner G. Colonic mucosal proliferation is related to serum deoxycholic acid levels. Cancer 1999;85:1664–9.
    1. Parkin DM, Muir CS. Cancer incidence in five continents. IARC Sci Publ 1992;120:45–173.
    1. Berg A. Nutrition, development and population growth. 29th ed Popul Bull; 1973;29:3–37.
    1. Sayin SI, Wahlstrom A, Felin J, Jantti S, Marschall HU, Bamberg K, Angelin B, Hyotylainen T, Oresic M, Backhed F. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab 2013;17:225–35.
    1. Devkota S, Wang Y, Musch MW, Leone V, Fehlner-Peach H, Nadimpalli A, Antonopoulos DA, Jabri B, Chang EB. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10-/- mice. Nature 2012;487:104–8.
    1. Louis P, Hold GL, Flint HJ. The gut microbiota, bacterial metabolites and colorectal cancer. Nat Rev Microbiol 2014;12:661–72.
    1. Nakanishi M, Chen Y, Qendro V, Miyamoto S, Weinstock E, Weinstock GM, Rosenberg DW. Effects of walnut consumption on colon carcinogenesis and microbial community structure. Cancer Prev Res 2016;9:692–703.
    1. Kris-Etherton PM. Walnuts decrease risk of cardiovascular disease: a summary of efficacy and biologic mechanisms. J Nutr 2014;144(Suppl):547S–54S.
    1. Zheng CJ, Yoo J-S, Lee T-G, Cho H-Y, Kim Y-H, Kim W-G. Fatty acid synthesis is a target for antibacterial activity of unsaturated fatty acids. FEBS Lett 2005;579:5157–62.
    1. Kankaanpää PE, Salminen SJ, Isolauri E, Lee YK. The influence of polyunsaturated fatty acids on probiotic growth and adhesion. FEMS Microbiol Lett 2001;194:149–53.
    1. Yu H-N, Zhu J, Pan W, Shen S-R, Shan W-G, Das UN. Effects of fish oil with a high content of n-3 polyunsaturated fatty acids on mouse gut microbiota. Arch Med Res 2014;45:195–202.
    1. Devillard E, McIntosh FM, Paillard D, Thomas NA, Shingfield KJ, Wallace RJ. Differences between human subjects in the composition of the faecal bacterial community and faecal metabolism of linoleic acid. Microbiology 2009;155:513–20.
    1. Gorissen L, Raes K, Weckx S, Dannenberger D, Leroy F, De Vuyst L, De Smet S. Production of conjugated linoleic acid and conjugated linolenic acid isomers by Bifidobacterium species. Appl Microbiol Biotechnol 2010;87:2257–66.
    1. Devillard E, McIntosh FM, Duncan SH, Wallace RJ. Metabolism of linoleic acid by human gut bacteria: different routes for biosynthesis of conjugated linoleic acid. J Bacteriol 2007;189:2566–70.
    1. Toma F, Andre C. Urolithins are the main urinary microbial-derived phenolic metabolites discriminating a moderate consumption of nuts in free-living subjects with diagnosed metabolic syndrome. J Agric Food Chem 2012;60:8930–40.
    1. Cardona F, Andrés-Lacueva C, Tulipani S, Tinahones FJ, Queipo-Ortuño MI. Benefits of polyphenols on gut microbiota and implications in human health. J Nutr Biochem 2013:1415–22.
    1. Larrosa M, García-Conesa MT, Espín JC, Tomás-Barberán FA. Ellagitannins, ellagic acid and vascular health. Mol Aspects Med 2010;31:513–39.
    1. Papoutsi Z, Kassi E, Chinou I, Halabalaki M, Skaltsounis LA, Moutsatsou P. Walnut extract (Juglans regia L.) and its component ellagic acid exhibit anti-inflammatory activity in human aorta endothelial cells and osteoblastic activity in the cell line KS483. Br J Nutr 2008;99:715–22.
    1. Tulipani S, Llorach R, Jáuregui O, López-Uriarte P, Garcia-Aloy M, Bullo M, Salas-Salvadó J, Andrés-Lacueva C. Metabolomics unveils urinary changes in subjects with metabolic syndrome following 12-week nut consumption. J Proteome Res 2011;10:5047–58.
    1. Tuohy KM, Conterno L, Gasperotti M, Viola R. Up-regulating the human intestinal microbiome using whole plant foods, polyphenols, and/or fiber. J Agric Food Chem 2012;60:8776–82.
    1. Ialonska DOB, Asimsetty SAGK, Chrader KEKS, Erreira DAF, Bialonska D, Kasimsetty SG, Schrader KK, Ferreira D. The effect of pomegranate (Punica granatum L.) byproducts and ellagitannins on the growth of human gut bacteria. J Agric Food Chem 2009;57:8344–9.
    1. Wang F, Yu T, Huang G, Cai D, Liang X, Su H, Zhu Z, Li D, Yang Y, Shen P, et al.Gut microbiota community and its assembly associated with age and diet in Chinese centenarians. J Microbiol Biotechnol 2015;25:1195–204.
    1. Biagi E, Franceschi C, Rampelli S, Severgnini M, Ostan R, Turroni S, Consolandi C, Quercia S, Scurti M, Monti D, et al.Gut microbiota and extreme longevity. Curr Biol 2016;26:1480–5.

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