Diet, the intestinal microbiota, and immune health in aging

Critical Reviews in Food Science and Nutrition

Volumn 58, Issue 4, 2018, Pages 651-661

  Clements, Sarah J ^a   R Carding, Simon ^a,b  

^a NORWICH RESEARCH PARK   (United Kingdom)

^b UNIVERSITY OF EAST ANGLIA   (United Kingdom)

Author keywords

Elderly; fat; fiber; immunosenescence; microbiota; protein; short chain fatty acids

Indexed keywords

FATTY ACIDS; FIBERS; HEALTH; HEALTH RISKS; OILS AND FATS; PROTEINS;

AGING POPULATION; DIETARY CARBOHYDRATES; ELDERLY; EXTRINSIC FACTORS; IMMUNOSENESCENCE; INTESTINAL HEALTHS; MICROBIOTAS; SHORT-CHAIN FATTY ACIDS;

IMMUNE SYSTEM;

AGED; AGING; DIET; HUMAN; IMMUNE SYSTEM; IMMUNOLOGY; INTESTINE; INTESTINE FLORA; MICROBIOLOGY; PHYSIOLOGY;

AGED; AGING; DIET; GASTROINTESTINAL MICROBIOME; HUMANS; IMMUNE SYSTEM; INTESTINES;

EID: 85025148026     PISSN: 10408398     EISSN: 15497852     Source Type: Journal    
DOI: 10.1080/10408398.2016.1211086     Document Type: Article

References (127)

1. Adlerberth, I., and Wold, A. E., (2009). Establishment of the gut microbiota in Western infants. Acta Paediatr. 98:229–238.
2. Albers, R., Van der Wielen, R., Brink, E., Hendriks, H., Dorovska-Taran, V., and Mohede, I., (2003). Effects of cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid (CLA) isomers on immune function in healthy men. Eur. J. Clin. Nutr. 57:595–603.
3. Alperovich, M., Neuman, M. I., Willett, W. C., and Curhan, G. C., (2007). Fatty acid intake and the risk of communityacquired pneumonia in U.S. women. Nutr. 23:196–202.
4. Arpaia, N., Campbell, C., Fan, X., Dikiy, S., van der Veeken, J., Liu, H., Cross, J. R., Pfeffer, K., Coffer, P. J., and Rudensky, A. Y., (2013). Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 504:451–455.
5. Arumugam, M., Raes, J., Pelletier, E., Le Paslier, D., Yamada, T., Mende, D. R., Fernandes, G. R., Tap, J., Bruls, T., and Batto, J. M., (2011). Enterotypes of the human gut microbiome. Nature. 473:174–180.
6. Atarashi, K., Tanoue, T., Oshima, K., Suda, W., Nagano, Y., Nishikawa, H., Fukuda, S., Saito, T., Narushima, S., and Hase, K., (2013). Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature. 500:232–236.
7. Atarashi, K., Tanoue, T., Shima, T., Imaoka, A., Kuwahara, T., Momose, Y., Cheng, G., Yamasaki, S., Saito, T., Ohba, Y., Taniguchi, T., Takeda, K., Hori, S., Ivanov, I. I., Umesaki, Y., Itoh, K., and Honda, K., (2011). Induction of colonic regulatory T cells by indigenous clostridium species. Science. 331:337–341.
8. Aw, D., Taylor-Brown, F., Cooper, K., and Palmer, D. B., (2009). Phenotypical and morphological changes in the thymic microenvironment from ageing mice. Biogerontology. 10:311–322.
9. Bartosch, S., Fite, A., Macfarlane, G. T., and McMurdo, M. E. T., (2004). Characterization of bacterial communities in feces from healthy elderly volunteers and hospitalized elderly patients by using real-time PCR and effects of antibiotic treatment on the fecal microbiota. Appl. Environ. Microbiol. 70:3575–3581.
10. Bates, B., Lennox, A., Prentice, A., Bates, C., Page, P., Nicholson, S., and Swan, G., (2014). National Diet and Nutrition Survey: Results from Years 1, 2, 3 and 4 (combined) of the Rolling Programme (2008/2009-2011/2012) 11, 09–2010.
11. Bates, B., Lennox, A., Prentice, A., Bates, C., and Swan, G., (2012). National Diet and Nutrition Survey: Headline results from Years 1, 2 and 3 (combined) of the Rolling Programme (2008/2009 - 2010/11). 1–79.
12. Bechoua, S., Dubois, M., Véricel, E., Chapuy, P., Lagarde, M., and Prigent, A.-F., (2003). Influence of very low dietary intake of marine oil on some fuctional aspects of immune cells in healthy elderly people. Br. J. Nutr. 89:523–531.
13. Bermudez‐Brito, M., Sahasrabudhe, N. M., Rösch, C., Schols, H. A., Faas, M. M., and Vos, P., (2015). The impact of dietary fibers on dendritic cell responses in vitro is dependent on the differential effects of the fibers on intestinal epithelial cells. Mol. Nutr. Food Res. 59:698–710.
14. Berndt, B. E., Zhang, M., Owyang, S. Y., Cole, T. S., Wang, T. W., Luther, J., Veniaminova, N. A., Merchant, J. L., Chen, C.-C., and Huffnagle, G. B., (2012). Butyrate increases IL-23 production by stimulated dendritic cells. Am. J. Physiol. Gastrointest. Liver Physiol. 303:G1384–G1392.
15. Biagi, E., Nylund, L., Candela, M., Ostan, R., Bucci, L., Pini, E., Nikkila, J., Monti, D., Satokari, R., Franceschi, C., Brigidi, P., and Vos, W., (2010). Through ageing, and beyond: Gut microbiota and inflammatory status in seniors and centenarians. Plos One. 5:14.
16. Birkett, A., Muir, J., Phillips, J., Jones, G., and O'Dea, K., (1996). Resistant starch lowers fecal concentrations of ammonia and phenols in humans. Am.J.Clin. Nutr. 63:766–772.
17. Bohmig, G. A., Krieger, P. M., Saemann, M. D., Wenhardt, C., Pohanka, E., and Zlabinger, G. J., (1997). N-butyratedownregulates the stimulatory function of peripheral blood-derived antigen-presenting cells: A potential mechanism for modulating T-cell responses by short-chain fatty acids. Immunology. 92:234–243.
18. Bunout, D., Hirsch, S., de la Maza, M., Munoz, C., Haschke, F., Steenhout, P., Klassen, P., Barrera, G., Gattas, V., and Petermann, M., (2002). Effects of prebiotics on the immune response to vaccination in the elderly. J. Parenter. Enteral. Nutr. 26:372–376.
19. Briceño, O., Lissina, A., Wanke, K., Afonso, G., Braun, A., Ragon, K., Miquel, T., Gostick, E., Papagno, L., and Stiasny, K., (2016). Reduced naïve CD8+ T-cell priming efficacy in elderly adults. Aging Cell. 15:14–21.
20. Camargo, A., Delgado-Lista, J., Garcia-Rios, A., Cruz-Teno, C., Yubero-Serrano, E. M., Perez-Martinez, P., Gutierrez-Mariscal, F. M., Lora-Aguilar, P., Rodriguez-Cantalejo, F., Fuentes-Jimenez, F., Jose Tinahones, F., Malagon, M. M., Perez-Jimenez, F., and Lopez-Miranda, J., (2012). Expression of proinflammatory, proatherogenic genes is reduced by the Mediterranean diet in elderly people. Br. J. Nutr. 108:500–508.
21. Campbell, W.W., Trappe, T. A., Wolfe, R. R., and Evans, W. J., (2001). The recommended dietary allowance for protein may not be adequate for older people to maintain skeletal muscle. J. Gerontol. Biol. Sci. Med. Sci. 56:M373–M380.
22. Castaneda, C., Charnley, J. M., Evans, W. J., and Crim, M. C., (1995). Elderly women accommodate to a low-protein diet with losses of body cell mass, muscle function, and immune response. Am. J. Clin. Nutr. 62:30–39.
23. Castle, S. C., (2000). Impact of age-related immune dysfunction on risk of infections. Z Gerontol. Geriatr. 33:341–349.
24. Christensen, K., Doblhammer, G., Rau, R., and Vaupel, J. W., (2009). Ageing populations: The challenges ahead. Lancet. 374:1196–1208.
25. Claesson, M. J., Jeffery, I. B., Conde, S., Power, S. E., O'Connor, E. M., Cusack, S., Harris, H. M. B., Coakley, M., Lakshminarayanan, B., O'Sullivan, O., Fitzgerald, G. F., Deane, J., O'Connor, M., Harnedy, N., O'Connor, K., O'Mahony, D., van Sinderen, D., Wallace, M., Brennan, L., Stanton, C., Marchesi, J. R., Fitzgerald, A. P., Shanahan, F., Hill, C., Ross, R. P., and O'Toole, P. W., (2012). Gut microbiota composition correlates with diet and health in the elderly. Nature. 488:178–184.
26. Coakley, M., Banni, S., Johnson, M., Mills, S., Devery, R., Fitzgerald, G., Paul Ross, R., and Stanton, C., (2009). Inhibitory effect of conjugated α-linolenic acid from bifidobacteria of intestinal origin on SW480 cancer cells. Lipids. 44:249–256.
27. Coakley, M., Ross, R. P., Nordgren, M., Fitzgerald, G., Devery, R., and Stanton, C., (2003). Conjugated linoleic acid biosynthesis by human-derived Bifidobacterium species. J. Appl. Microbiol. 94:138–145.
28. Cultrone, A., Tap, J., Lapaque, N., Doré, J., and Blottière, H. M., (2015). Metagenomics of the human intestinal tract: From who is there to what is done there. Curr. Opin. Food Sci. 4:64–68.
29. Czesnikiewicz-Guzik, M., Lee, W.-W., Cui, D., Hiruma, Y., Lamar, D. L., Yang, Z.-Z., Ouslander, J. G., Weyand, C. M., and Goronzy, J. J., (2008). T cell subset-specific susceptibility to aging. Clin. Immun. 127:107–118.
30. Daly, R. M., Gianoudis, J., Prosser, M., Kidgell, D., Ellis, K. A., O'Connell, S., and Nowson, C. A., (2015). The effects of a protein enriched diet with lean red meat combined with a multi-modal exercise program on muscle and cognitive health and function in older adults: Study protocol for a randomised controlled trial. Trials. 16:1–16.
31. Daly, R. M., O'Connell, S. L., Mundell, N. L., Grimes, C. A., Dunstan, D. W., and Nowson, C. A., (2014). Protein-enriched diet, with the use of lean red meat, combined with progressive resistance training enhances lean tissue mass and muscle strength and reduces circulating IL-6 concentrations in elderly women: A cluster randomized controlled trial. Am. J. Clin. Nutr. 99:899–910.
32. Daniel, H., Gholami, A. M., Berry, D., Desmarchelier, C., Hahne, H., Loh, G., Mondot, S., Lepage, P., Rothballer, M., and Walker, A., (2014). High-fat diet alters gut microbiota physiology in mice. ISME J. 8:295–308.
33. De Filippis, F., Pellegrini, N., Vannini, L., Jeffery, I. B., La Storia, A., Laghi, L., Serrazanetti, D. I., Di Cagno, R., Ferrocino, I., and Lazzi, C., (2015). High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome. Gut. 65:1812–1821.
34. De Filippo, C., Cavalieri, D., Di Paola, M., Ramazzotti, M., Poullet, J. B., Massart, S., Collini, S., Pieraccini, G., and Lionetti, P., (2010). Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc. Natl. Acad. Sci. 107:14691–14696.
35. Dedoussis, G. V., Kanoni, S., Mariani, E., Cattini, L., Herbein, G., Fulop, T., Varin, A., Rink, L., Jajte, J., Monti, D., Marcellini, F., Malavolta, M., and Mocchegiani, E., (2008). Mediterranean diet and plasma concentration of inflammatory markers in old and very old subjects in the ZINCAGE population study. Clin. Chem. Lab. Med. 46:990–996.
36. DESA, UN (2002). World Population Ageing 1950–2050. Report, United Nations' Department of Economic and Social Affairs Population Division (DESA).
37. Devillard, E., McIntosh, F. M., Paillard, D., Thomas, N. A., Shingfield, K. J., and Wallace, R. J., (2009). Differences between human subjects in the composition of the faecal bacterial community and faecal metabolism of linoleic acid. Microbiology. 155:513–520.
38. Duncan, S. H., Lobley, G., Holtrop, G., Ince, J., Johnstone, A., Louis, P., and Flint, H., (2008). Human colonic microbiota associated with diet, obesity and weight loss. Int. J. Obesity. 32:1720–1724.
39. Dunstan, J. A., Mori, T. A., Barden, A., Beilin, L. J., Taylor, A. L., Holt, P. G., and Prescott, S. L., (2003). Fish oil supplementation in pregnancy modifies neonatal allergen-specific immune responses and clinical outcomes in infants at high risk of atopy: A randomized, controlled trial. J. Allergy Clin. Immun. 112:1178–1184.
40. Fanaro, S., Chierici, R., Guerrini, P., and Vigi, V., (2003). Intestinal microflora in early infancy: Composition and development. Acta Pediatr. 92:48–55.
41. Forsey, R. J., Thompson, J. M., Ernerudh, J., Hurst, T. L., Strindhall, J., Johansson, B., Nilsson, B. O., and Wikby, A., (2003). Plasma cytokine profiles in elderly humans. Mech. Ageing Dev. 124:487–493.
42. Franceschi, C., Capri, M., Monti, D., Giunta, S., Olivieri, F., Sevini, F., Panourgia, M. P., Invidia, L., Celani, L., Scurti, M., Cevenini, E., Castellani, G. C., and Salvioli, S., (2007). Inflammaging and anti-inflammaging: A systemic perspective on aging and longevity emerged from studies in humans. Mech. Ageing Dev. 128:92–105.
43. Freeman, S. L., Fisher, L., German, J. B., Leung, P. S., Prince, H., Selmi, C., Naguwa, S. M., and Gershwin, M. E., (2010). Dairy proteins and the response to pneumovax in senior citizens: A randomized, double‐blind, placebo‐controlled pilot study. Ann. New York Acad. Sci. 1190:97–103.
44. Furusawa, Y., Obata, Y., Fukuda, S., Endo, T. A., Nakato, G., Takahashi, D., Nakanishi, Y., Uetake, C., Kato, K., and Kato, T., (2013). Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. 504:446–450.
45. Gabert, L., Vors, C., Louche‐Pélissier, C., Sauvinet, V., Lambert‐Porcheron, S., Drai, J., Laville, M., Désage, M., and Michalski, M. C., (2011). 13C tracer recovery in human stools after digestion of a fat‐rich meal labelled with [1, 1, 1‐13C3] tripalmitin and [1, 1, 1‐13C3] triolein. Rapid Commun. Mass Spectrom. 25:2697–2703.
46. Gibson, A., J. D., Edgar, C. E., Neville, S. E., Gilchrist, M. C., McKinley, C. C., Patterson, I. S., Young and J. V., Woodside. (2012). Effect of fruit and vegetable consumption on immune function in older people: A randomized controlled trial. Am. J. Clin. Nutr. 96(6):1429–1436. doi: 10.3945/ajcn.112.039057.
47. Gorissen, L., Raes, K., Weckx, S., Dannenberger, D., Leroy, F., De Vuyst, L., and De Smet, S., (2010). Production of conjugated linoleic acid and conjugated linolenic acid isomers by Bifidobacterium species. Appl. Microbiol. Biotechnol. 87:2257–2266.
48. Grassi, M., Petraccia, L., Mennuni, G., Fontana, M., Scarno, A., Sabetta, S., and Fraioli, A., (2011). Changes, functional disorders, and diseases in the gastrointestinal tract of elderly. Nutr. Hospitalaria. 26:659–668.
49. Grieger, J. A., Miller, M. D., and Cobiac, L., (2014). Investigation of the effects of a high fish diet on inflammatory cytokines, blood pressure, and lipids in healthy older Australians. Food. Nutr. Res. 58:20369.
50. Guigoz, Y., Rochat, F., Perruisseau-Carrier, G., Rochat, I., and Schiffrin, E.J., (2002). Effects of oligosaccharide on the faecal flora and non-specific immune system in elderly people. Nutr. Res. 22:13–25.
51. Hamer, H. M., Jonkers, D., Venema, K., Vanhoutvin, S., Troost, F. J., and Brummer, R. J., (2008). Review article: The role of butyrate on colonic function. Aliment. Pharmacol. Ther. 27:104–119.
52. He, F., Ouwehand, A. C., Isolauri, E., Hosoda, M., Benno, Y., and Salminen, S., (2001). Differences in composition and mucosal adhesion of bifidobacteria isolated from healthy adults and healthy seniors. Curr. Microbiol. 43:351–354.
53. He, K., Liu, K., Daviglus, M. L., Jenny, N. S., Mayer-Davis, E., Jiang, R., Steffen, L., Siscovick, D., Tsai, M., and Herrington, D., (2009). Associations of dietary long-chain n-3 polyunsaturated fatty acids and fish with biomarkers of inflammation and endothelial activation (from the multi-ethnic study of atherosclerosis [MESA]). Am. J. Cardiol. 103:1238–1243.
54. Hickson, M., (2006). Malnutrition and ageing. Postgrad. Med. J. 82:2–8.
55. Hopkins, M. J., Sharp, R., and Macfarlane, G. T., (2002). Variation in human intestinal microbiota with age. Digest. Liver Dis. 34:S12–S18.
56. Health & Social Care Information Centre, Adult Social Care Statistics Team (ASCST). (2015). Community Care Statistics, Social Services Activity, England–2014–2015. HSCIC. http://www.hscic.gov.uk/pubs/commcaressa1415
57. Hughes, R., Pollock, J. R. A., and Bingham, S., (2002). Effect of vegetables, tea, and soy on endogenous N-Nitrosation, fecal ammonia, and fecal water genotoxicity during a high red meat diet in humans. Nutr. Cancer. 42:70–77.
58. Kelley, D., Simon, V., Taylor, P., Rudolph, I., Benito, P., Nelson, G., Mackey, B., and Erickson, K., (2001). Dietary supplementation with conjugated linoleic acid increased its concentration in human peripheral blood mononuclear cells, but did not alter their function. Lipids. 36:669–674.
59. Kelley, D., Taylor, P., Rudolph, I., Benito, P., Nelson, G., Mackey, B., and Erickson, K., (2000). Dietary conjugated linoleic acid did not alter immune status in young healthy women. Lipids. 35:1065–1071.
60. Kew, S., Banerjee, T., Minihane, A. M., Finnegan, Y. E., Williams, C. M., and Calder, P. C., (2003). Relation between the fatty acid composition of peripheral blood mononuclear cells and measures of immune cell function in healthy, free-living subjects aged 25–72 y. Am. J. Clin. Nutr. 77:1278–1286.
61. Khan, N., Shariff, N., Cobbold, M., Bruton, R., Ainsworth, J. A., Sinclair, A. J., Nayak, L., and Moss, P. A., (2002). Cytomegalovirus seropositivity drives the CD8 T cell repertoire toward greater clonality in healthy elderly individuals. J. Immun. 169:1984–1992.
62. Koeth, R. A., Wang, Z., Levison, B. S., Buffa, J. A., Sheehy, B. T., Britt, E. B., Fu, X., Wu, Y., Li, L., and Smith, J. D., (2013). Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nature Med. 19:576–585.
63. Kraemer, W. J., Hatfield, D. L., Comstock, B. A., Fragala, M. S., Davitt, P. M., Cortis, C., Wilson, J. M., Lee, E. C., Newton, R. U., and Dunn-Lewis, C., (2014). Influence of HMB supplementation and resistance training on cytokine responses to resistance exercise. J. Am. Coll. Nutr. 33:247–255.
64. Kukkonen, K., Savilahti, E., Haahtela, T., Juntunen-Backman, K., Korpela, R., Poussa, T., Tuure, T., and Kuitunen, M., (2007). Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: A randomized, double-blind, placebo-controlled trial. J. Allergy Clin. Immunol. 119:192–198.
65. Lecerf, J.-M., Dépeint, F., Clerc, E., Dugenet, Y., Niamba, C. N., Rhazi, L., Cayzeele, A., Abdelnour, G., Jaruga, A., and Younes, H., (2012). Xylo-oligosaccharide (XOS) in combination with inulin modulates both the intestinal environment and immune status in healthy subjects, while XOS alone only shows prebiotic properties. Brit. J.Nutr. 108:1847–1858.
66. Ley, R. E., Turnbaugh, P. J., Klein, S., and Gordon, J. I., (2006). Microbial ecology: Human gut microbes associated with obesity. Nature. 444:1022–1023.
67. Liu, L., Li, L., Min, J., Wang, J., Wu, H., Zeng, Y., Chen, S., and Chu, Z., (2012). Butyrate interferes with the differentiation and function of human monocyte-derived dendritic cells. Cell. Immunol. 277:66–73.
68. Man, A. L., Gicheva, N., and Nicoletti, C., (2014). The impact of ageing on the intestinal epithelial barrier and immune system. Cell. Immunol. 289:112–118.
69. Marchesi, J. R., Adams, D. H., Fava, F., Hermes, G. D., Hirschfield, G. M., Hold, G., Quraishi, M. N., Kinross, J., Smidt, H., and Tuohy, K. M., (2016). The gut microbiota and host health: A new clinical frontier. Gut. 65:330–339.
70. Maukonen, J., and Saarela, M., (2015). Human gut microbiota: Does diet matter? Proc. Nutr. Soc. 74:23–36.
71. McIntosh, F. M., Shingfield, K. J., Devillard, E., Russell, W. R., and Wallace, R. J., (2009). Mechanism of conjugated linoleic acid and vaccenic acid formation in human faecal suspensions and pure cultures of intestinal bacteria. Microbiology. 155:285–294.
72. Merchant, A. T., Curhan, G. C., Rimm, E. B., Willett, W. C., and Fawzi, W. W., (2005). Intake of n-6 and n-3 fatty acids and fish and risk of community-acquired pneumonia in US men. Am. J. Clin. Nutr. 82:668–674.
73. Meydani, S. N., Endres, S., Woods, M. M., Goldin, B. R., Soo, C., Morrill-Labrode, A., Dinarello, C. A., and Gorbach, S. L., (1991). Oral (n-3) fatty acid supplementation suppresses cytokine production and lymphocyte proliferation: comparison between young and older women. J. Nutr. 121:547–555.
74. Mena, M.-P., Sacanella, E., Vazquez-Agell, M., Morales, M., Fito, M., Escoda, R., Serrano-Martinez, M., Salas-Salvado, J., Benages, N., Casas, R., Lamuela-Raventos, R. M., Masanes, F., Ros, E., and Estruch, R., (2009). Inhibition of circulating immune cell activation: A molecular antiinflammatory effect of the Mediterranean diet. Am. J. Clin. Nutr. 89:248–256.
75. Minot, S., Bryson, A., Chehoud, C., Wu, G. D., Lewis, J. D., and Bushman, F. D., (2013). Rapid evolution of the human gut virome. Proc. Natl. Acad. Sci. 110:12450–12455.
76. Murakami, S., Kurihara, S., Koikawa, N., Nakamura, A., Aoki, K., Yosigi, H., Sawaki, K., and Ohtani, M., (2009). Effects of oral supplementation with cystine and theanine on the immune function of athletes in endurance exercise: Randomized, double-blind, placebo-controlled trial. Biosci. Biotechnol. Biochem. 73:817–821.
77. Murphy, J. L., Jones, A., Brookes, S., and Wootton, S. A., (1995). The gastrointestinal handling and metabolism of [1-13C] palmitic acid in healthy women. Lipids. 30:291–298.
78. Nguyen, T. L. A., Vieira-Silva, S., Liston, A., and Raes, J., (2015). How informative is the mouse for human gut microbiota research? Dis. Models Mech. 8:1–16.
79. Nugent, A., Roche, H., Noone, E., Long, A., Kelleher, D., and Gibney, M., (2005). The effects of conjugated linoleic acid supplementation on immune function in healthy volunteers. Eur. J. Clin. Nutr. 59:742–750.
80. O'Toole, P. W., and Brigidi, P., (2013). The intestinal microbiota and aging. In: Guarino, A., and Walker, W. A., Eds., Probiotic Bacteria and Their Effect on Human Health and Well-Being. Karger Medical and Scientific Publishers, Basel(Switzerland), pp. 25–31.
81. O'Shea, M., Bassaganya-Riera, J., and Mohede, I. C., (2004). Immunomodulatory properties of conjugated linoleic acid. Am. J. Clin. Nutr. 79:1199S–1206S.
82. Office for National Statistics (ONS), OFNS. (2014). Changes in the Older Care Home Population at Local Authority Level Between 2001 and 2011.
83. Ouwehand, A. C., Isolauri, E., Kirjavainen, P. V., and Salminen, S. J., (1999). Adhesion of four Bifidobacterium strains to human intestinal mucus from subjects in different age groups. FEMS Microbiol. Lett. 172:61–64.
84. Palmer, C., Bik, E. M., DiGiulio, D. B., Relman, D. A., and Brown, P. O., (2007). Development of the human infant intestinal microbiota. PLoS Biol. 5:e177.
85. Pischon, T., Hankinson, S. E., Hotamisligil, G. S., Rifai, N., Willett, W. C., and Rimm, E. B., (2003). Habitual dietary intake of n-3 and n-6 fatty acids in relation to inflammatory markers among US men and women. Circulation. 108:155–160.
86. Plé, Coline, Jérôme, Breton, Catherine, Daniel, and Benoît, Foligné. (2015). Maintaining gut ecosystems for health: Are transitory food bugs stowaways or part of the crew? Int. J. Food Microbiol. 213:139–143.
87. Qin, J., Li, R., Raes, J., Arumugam, M., Burgdorf, K. S., Manichanh, C., Nielsen, T., Pons, N., Levenez, F., and Yamada, T., (2010). A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 464:59–65.
88. Rayner, C. K., and Horowitz, M., (2013). Physiology of the ageing gut. Curr. Opin. Clin. Nutr. Metab. Care. 16:33–38.
89. Rees, D., Miles, E. A., Banerjee, T., Wells, S. J., Roynette, C. E., Wahle, K. W., and Calder, P. C., (2006). Doserelated effects of eicosapentaenoic acid on innate immune function in healthy humans: a comparison of young and older men. Am. J. Clin. Nutr. 83:331–342.
90. Reques Velasco, P., (2008). Longevity and geographical location.Geodemographic analysis of the centenarian population in Spain. Rev. Esp. deGeriatria Gerontol. 43:96–105.
91. Reyes, A., Haynes, M., Hanson, N., Angly, F. E., Heath, A. C., Rohwer, F., and Gordon, J. I., (2010). Viruses in the faecalmicrobiota of monozygotic twins and their mothers. Nature. 466:334–338.
92. Richter, E. A., Kiens, B., Raben, A., Tvede, N., and Pedersen, B. K., (1991). Immune parameters in male atheletes after a lacto-ovo vegetarian diet and a mixed Western diet. Med. Sci. Sport. Exer. 23:517–521.
93. Ruth, M., and Field, C., (2013). The immune modifying effects of amino acids on gut-associated lymphoid tissue. J. Anim. Sci. Biotechnol. 4:27.
94. Ryan-Borchers, T. A., Park, J. S., Chew, B. P., McGuire, M. K., Fournier, L. R., and Beerman, K. A., (2006). Soy isoflavones modulate immune function in healthy postmenopausal women. Am. J. Clin. Nutr. 83:1118–1125.
95. Schepers, E., Meert, N., Glorieux, G., Goeman, J., Van der Eycken, J., and Vanholder, R., (2007). P-cresylsulphate, the main in vivo metabolite of p-cresol, activates leucocyte free radical production. Nephrol. Dial.Transpl. 22:592–596.
96. Scholz, J. L., Diaz, A., Riley, R. L., Cancro, M. P., and Frasca, D., (2013). A comparative review of aging and B cell function in mice and humans. Curr. Opin. Immunol. 25:504–510.
97. Schwartz, S., Friedberg, I., Ivanov, I. V., Davidson, L. A., Goldsby, J. S., Dahl, D. B., Herman, D., Wang, M., Donovan, S. M., and Chapkin, R. S., (2012). A metagenomic study of diet-dependent interaction between gut microbiota and host in infants reveals differences in immune response. Genome Biol. 13:R32.
98. Scott, K. P., Gratz, S. W., Sheridan, P. O., Flint, H. J., and Duncan, S. H., (2013). The influence of diet on the gut microbiota. Pharmacol. Res. 69:52–60.
99. Silvester, K. R., Bingham, S. A., Pollock, J. R. A., Cummings, J. H., and O'Neill, I. K., (1997). Effect of meat and resistant starch on fecal excretion of apparent N‐nitroso compounds and ammonia from the human large bowel. Nutr. Cancer. 29:13–23.
100. Simonsen, L., Taylor, R. J., Young-Xu, Y., Haber, M., May, L., and Klugman, K. P., (2011). Impact of pneumococcal conjugate vaccination of infants on pneumonia and influenza hospitalization and mortality in all age groups in the United States. MBio 2(1):e00309–10.
101. Smith, P. M., Howitt, M. R., Panikov, N., Michaud, M., Gallini, C. A., Bohlooly-Y, M., Glickman, J. N., and Garrett, W. S., (2013). The microbial metabolites, short-chain fatty acids, regulate colonic treg cell homeostasis. Science. 341:569–573.
102. Solís, G., de los Reyes-Gavilan, C. G., Fernández, N., Margolles, A., and Gueimonde, M., (2010). Establishment and development of lactic acid bacteria and bifidobacteriamicrobiota in breast-milk and the infant gut. Anaerobe. 16:307–310.
103. Song, H., Grant, I., Rotondo, D., Mohede, I., Sattar, N., Heys, S., and Wahle, K., (2005). Effect of CLA supplementation on immune function in young healthy volunteers. Eur. J. Clin. Nutr. 59:508–517.
104. Stachowska, E., Dolegowska, B., Dziedziejko, V., Rybicka, M., Kaczmarczyk, M., Bober, J., Rac, M., Machalinski, B., and Chlubek, D., (2009). Prostaglandin E2 (PGE2) and thromboxane A2 (TXA2) synthesis is regulated by conjugated linoleic acids (CLA) in human macrophages. Acta Physiologica Polonica. 60:77.
105. Tang, W. W., Wang, Z., Levison, B. S., Koeth, R. A., Britt, E. B., Fu, X., Wu, Y., and Hazen, S. L., (2013). Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N. Engl. J. Med. 368:1575–1584.
106. Tap, J., Furet, J. P., Bensaada, M., Philippe, C., Roth, H., Rabot, S., Lakhdari, O., Lombard, V., Henrissat, B., and Corthier, G., (2015). Gut microbiota richness promotes its stability upon increased dietary fibre intake in healthy adults. Environ. Microbiol. 17:4954–4964.
107. Taub, D. D., and Longo, D. L., (2005). Insights into thymic aging and regeneration. Immunol.Rev. 205:72–93.
108. Thies, F., Nebe-von-Caron, G., Powell, J. R., Yaqoob, P., Newsholme, E. A., and Calder, P. C., (2001). Dietary supplementation with gamma-linolenic acid or fish oil decreases T lymphocyte proliferation in healthy older humans. J. Nutr. 131:1918–1927.
109. Thompson, L., and Spiller, R. C., (1995). Impact of polyunsaturated fatty acids on human colonic bacterial metabolism: An in vitro and in vivo study. Brit. J. Nutr. 74:733–741.
110. Tremaroli, V., and Bäckhed, F., (2012). Functional interactions between the gut microbiota and host metabolism. Nature. 489:242–249.
111. Tricon, S., Burdge, G. C., Kew, S., Banerjee, T., Russell, J. J., Grimble, R. F., Williams, C. M., Calder, P. C., and Yaqoob, P., (2004). Effects of cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid on immune cell function in healthy humans. Am. J. Clin. Nutr. 80:1626–1633.
112. Turnbaugh, P. J., and Gordon, J. I., (2009). The core gutmicrobiome, energy balance and obesity. J. Physiol. 587:4153–4158.
113. Turnbaugh, P. J., Ley, R. E., Mahowald, M. A., Magrini, V., Mardis, E. R., and Gordon, J. I., (2006). An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 444:1027–1131.
114. Virgin, H. W., (2014). The virome in mammalian physiology and disease. Cell. 157:142–150.
115. Vulevic, J., Drakoularakou, A., Yaqoob, P., Tzortzis, G., and Gibson, G. R., (2008). Modulation of the fecal microflora profile and immune function by a novel transgalactooligosaccharide mixture (B-GOS) in healthy elderly volunteers. Am. J. Clin. Nutr. 88:1438–1446.
116. Wikby, A., Johansson, B., Olsson, J., Löfgren, S., Nilsson, B.-O., andFerguson, F., (2002). Expansions of peripheral blood CD8 T-lymphocyte subpopulations and an association with cytomegalovirus seropositivity in the elderly: The Swedish NONA immune study. Exp. Gerontol. 37:445–453.
117. Wilson, K., Rosenberg, M. W., and Abonyi, S., (2011). Aboriginal peoples, health and healing approaches: The effects of age and place on health. Soc. Sci. Med. 72:355–364.
118. Wilson, T., (2014). New population and life expectancy estimates for the Indigenous population of Australia's Northern Territory, 1966–2011. PLoS One. 9:e97576.
119. Windey, K., De Preter, V., and Verbeke, K., (2012). Relevance of protein fermentation to gut health. Mol. Nutr. Food Res. 56:184–196.
120. Wolfe, R. R., Miller, S. L., and Miller, K. B., (2008). Optimal protein intake in the elderly. Clin. Nutr. 27:675–684.
121. Woodmansey, E. J., (2007). Intestinal bacteria and ageing. J. Appl. Microbiol. 102:1178–1186.
122. Woodmansey, E. J., McMurdo, M. E. T., Macfarlane, G. T., and Macfarlane, S., (2004). Comparison of compositions and metabolic activities of fecal microbiotas in young adults and in antibiotic-treated and non-antibiotic-treated elderly subjects. Appl. Environ. Microbiol. 70:6113–6122.
123. Wostmann, B. S., (1981). The germfree animal in nutritional studies. Annu. Rev. Nutr. 1:257–279.
124. Wu, D., Meydani, M., Leka, L. S., Nightingale, Z., Handelman, G. J., Blumberg, J. B., and Meydani, S. N., (1999). Effect of dietary supplementation with black currant seed oil on the immune response of healthy elderly subjects. Am. J. Clin. Nutr. 70:536–543.
125. Yang, J., and Rose, D. J., (2014). Long-term dietary pattern of fecal donor correlates with butyrate production and markers of protein fermentation during in vitro fecal fermentation. Nutr. Res. 34:749–759.
126. Zhu, K., Devine, A., Suleska, A., Tan, C., Toh, C., Kerr, D., and Prince, R., (2010). Adequacy and change in nutrient and food intakes with aging in a seven-year cohort study in elderly women. J. Nutr. Health. Aging. 14:723–729.
127. Zimmer, J., Lange, B., Frick, J.-S., Sauer, H., Zimmermann, K., Schwiertz, A., Rusch, K., Klosterhalfen, S., and Enck, P., (2012). A vegan or vegetarian diet substantially alters the human colonic faecalmicrobiota. Eur. J. Clin. Nutr. 66:53–60.