短鏈脂肪酸與嬰兒異位性皮膚炎及高脂飲食小鼠腸道免疫之相關性探討

Study on the association of short chain fatty acids with infant atopic dermatitis and intestinal immunity of high-fat diet fed mice

10.6342/NTU201703241

沈瑩柔

異位性皮膚炎 ； 脂肪酸 ； 短鏈脂肪酸 ； 母乳 ； 腸道免疫 ； 比菲德氏菌 ； 益生菌 ； 寒天寡醣 ； atopic dermatitis ； fatty acids ； short chain fatty acids ； breast milk ； intestinal immunity ； Bifidobacterium ； probiotics ； agaro-oligosaccharide

臺灣大學生化科技學系學位論文

2017年

碩士

林璧鳳

繁體中文

短鏈脂肪酸為腸道菌代謝水溶性纖維的產物，與腸道免疫的關係日益受到重視，目前被認為具有抗發炎的作用，能改善氣喘、肥胖、腸道發炎等疾病。故本研究探討短鏈脂肪酸是否與過敏疾病和腸道免疫反應有關。分別檢測異位性皮膚炎嬰兒所哺餵的母乳，及給予高油飲食小鼠添加益生質寒天寡醣，探討短鏈脂肪酸與免疫反應的相關性。第一部份實驗樣品於臺大醫院小兒科過敏門診，收集6個月齡以下罹患異位性皮膚炎嬰兒的母乳，分別測定短鏈脂肪酸 (C2~C4) 及中長鏈脂肪酸 (C8-C24) 含量，並對母親進行1個月的飲食頻率問卷調查。結果顯示，異位性皮膚炎嬰兒所攝取母乳的MUFAs、n-3 PUFAs、palmitic acid及arachidonic acid脂肪酸百分比較高，而capric acid和myristic acid較低，短鏈脂肪酸則無顯著差異。第二部分以高油飲食小鼠模式，探討短鏈脂肪酸和腸道菌組成對腸道免疫之影響。實驗設計為給予5週齡C57BL/6J小鼠28% 高油飼料 (HF組，油脂熱量為51%)，高油添加3%寒天寡醣 (HF-AOS組)、或添加109/day CFU市售益生菌粉末 (HF-PRO組)。餵飼8週後犧牲，分析脾臟、腸繫膜淋巴結與皮耶式體的免疫指標，盲腸和糞便的短鏈脂肪酸以及糞便IgA含量。結果顯示，高油飲食造成小鼠糞便比菲德氏菌屬顯著下降，而HF-PRO組添加益生菌確實顯著增加糞便比菲德氏菌屬的含量。HF-PRO組小鼠MLN的CD103+樹突細胞比例也較高，PP細胞分泌IL-2顯著較HF組低，脾臟細胞和MLN細胞IL-17分泌量趨勢較HF組高，而脾臟細胞IL-2分泌量顯著較HF組高。HF-AOS組母鼠宮旁脂顯著最輕，血清和肝臟脂質含量顯著最少，但在糞便中顯著最多，顯示寒天寡醣可能會抑制脂質吸收。HF-AOS組盲腸顯著最重，糞便的腸桿菌科含量略高，盲腸及糞便的短鏈脂肪酸含量顯著最低。MLN細胞分泌IFN-γ有增加的趨勢，糞便IgA的濃度顯著最高。另外大腸組織切片也觀察到絨毛破損、黏液分泌量較少，推測本實驗添加寒天寡醣的量偏高可能吸附腸道水份，造成黏膜細胞受損，腸道蠕動較快速，使得腸道菌無法利用寒天寡醣發酵生成短鏈脂肪酸，使腸道免疫趨向抵抗感染的發炎反應。綜合以上，本研究發現母乳有較低比率的SFAs、較高比率的MUFAs及n-3 PUFAs可能與嬰兒異位性皮膚炎相關，但未呈現母乳的短鏈脂肪酸含量與嬰兒異位性皮膚炎有關。高油飲食小鼠添加寒天寡醣劑量可能過高，導致小鼠輕微腹瀉且腸道處於較發炎的狀態，而高油飲食添加益生菌，顯著降低PP細胞IL-2的分泌量，但有促進MLN細胞分泌IL-17及脾臟細胞分泌IL-2和IL-17的趨勢，意喻高油飲食下補充益生菌，改善腸道免疫的效果有限。

The microbial metabolites short chain fatty acids (SCFAs) are fermented from soluble dietary fiber. Significant attention has been focused on the relationship between SCFAs and intestinal immunity. SCFAs was shown to have the anti-inflammatory effect, and could ameliorate asthma, obesity, intestinal inflammation. Thus, the aim of this study is to investigate the association of SCFAs with allergic disease and intestinal immunity. To investigate the effect of SCFAs on immune response, we analyzed breast milk from the infant with atopic dermatitis (AD), and related parameters from high-fat diet fed mice supplemented with prebiotics agaro-oligosaccharide. In the first part, we cooperated with the Department of the Pediatric at NTU hospital to collect breast milk from infants’ mothers to detect the C8-C24 fatty acids composition and short chain fatty acids (SCFAs) concentration. We also analyzed maternal diet by FFQ (food frequency questionnaire). The results showed that the percentages of MUFAs, n-3 PUFAs, palmitic acid and arachidonic acid of breast milk were higher, and capric acid and myristic acid were lower in the AD group than the health group. SCFAs concentration had no significant difference between two groups. In the second part, we investigated the effect of SCFAs and microbiota on intestinal immunity in high-fat diet fed mice. 5 week-old C57BL/6J mice were fed either 28% fat diet (HF group), HF containing 3% AOS (HF-AOS group) or 109/day CFU probiotics (HF-PRO group) for 8 weeks. Immune indicators of spleen, MLN, PP, fecal and cecal SCFAs, and fecal IgA were also detected. The results showed that fecal Bifidobacterium was decreased in high-fat diet fed mice, and probiotics increased fecal Bifidobacterium in the HF-PRO group. CD103+ dendritic cell percentage was increased in MLN, IL-2 secretion from PP was lower, IL-17 secretion from MLN was higher, and IL-2 and IL-17 secretion from splenocytes were higher in the HF-PRO group compared with the HF group. The parametrial white adipose from female mice was the lightest in the HF-AOS group. The lipid content in serum and liver were the least, but the lipid content was the highest in the HF-AOS group. These data showed that AOS might inhibit the absorption of lipid. The cecum was heaviest, fecal Enterobacteriaceae increased, and fecal and cecal SCFAs were decreased in the HF-AOS group. Fecal IgA and IFN-γ secreted from MLN cells were increased in the HF-AOS group. Evaluating colon histomorphology from H&E and PAS stained, the villous were damaged and with less mucin. We surmised that the mucus was damaged due to the high dose of AOS and its water containing ability. It also led to pro-inflammatory response in mice intestine with less SCFAs production. In conclusion, the lower percentage of SFAs and the higher percentage of MUFAs and n-3 PUFAs might be associated with infant AD. But there was no association between breast milk SCFAs and infant AD. Our results found out that 3% AOS in high-fat diet fed mice might lead to dysbiosis and inflammation in mice intestine, which might due to overdose. High-fat diet with probiotics could decrease IL-2 secretion from PP, but tend to promote IL-17 secretion in MLN and IL-2 and IL-17 secretion in spleen. Thus, the results indicated that the effect of probiotics on high-fat diet fed mice was limited.

1. Adam, C. L., Gratz, S. W., Peinado, D. I., Thomson, L. M., Garden, K. E., Williams, P. A., et al. (2016). Effects of dietary fibre (pectin) and/or increased protein (casein or pea) on satiety, body weight, adiposity and caecal fermentation in high fat diet-induced obese rats. PLoS One, 11(5).
   連結：
2. Adam, C. L., Williams, P. A., Dalby, M. J., Garden, K., Thomson, L. M., Richardson, A. J., et al. (2014). Different types of soluble fermentable dietary fibre decrease food intake, body weight gain and adiposity in young adult male rats. Nutrition & Metabolism, 11, 36.
   連結：
3. Agrawal, R., Wisniewski, J. A., & Woodfolk, J. A. (2011). The role of regulatory T cells in atopic dermatitis. Current Problems in Dermatology, 41, 112-124.
   連結：
4. Akdis, M., Verhagen, J., Taylor, A., Karamloo, F., Karagiannidis, C., Crameri, R., et al. (2004). Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells. Journal of Experimental Medicine, 199(11), 1567-1575.
   連結：
5. Andreas, N. J., Kampmann, B., & Mehring Le-Doare, K. (2015). Human breast milk: A review on its composition and bioactivity. Early Human Development, 91(11), 629-635.
   連結：
6. Annacker, O., Coombes, J. L., Malmstrom, V., Uhlig, H. H., Bourne, T., Johansson-Lindbom, B., et al. (2005). Essential role for CD103 in the T cell-mediated regulation of experimental colitis. Journal of Experimental Medicine, 202(8), 1051-1061.
   連結：
7. Asher, M. I., Montefort, S., Bjorksten, B., Lai, C. K., Strachan, D. P., Weiland, S. K., et al. (2006). Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys. Lancet, 368(9537), 733-743.
   連結：
8. Asseman, C., Mauze, S., Leach, M. W., Coffman, R. L., & Powrie, F. (1999). An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation. Journal of Experimental Medicine, 190(7), 995-1004.
   連結：
9. Atarashi, K., Nishimura, J., Shima, T., Umesaki, Y., Yamamoto, M., Onoue, M., et al. (2008). ATP drives lamina propria T(H)17 cell differentiation. Nature, 455(7214), 808-810.
   連結：
10. Bekiaris, V., Persson, E. K., & Agace, W. W. (2014). Intestinal dendritic cells in the regulation of mucosal immunity. Immunological Reviews, 260(1), 86-101.
    連結：
11. Berg, A. H., & Scherer, P. E. (2005). Adipose tissue, inflammation, and cardiovascular disease. Circulation Research, 96(9), 939-949.
    連結：
12. Bergmann, R. L., Diepgen, T. L., Kuss, O., Bergmann, K. E., Kujat, J., Dudenhausen, J. W., et al. (2002). Breastfeeding duration is a risk factor for atopic eczema. Clinical and Experimental Allergy, 32(2), 205-209.
    連結：
13. Bergtold, A., Desai, D. D., Gavhane, A., & Clyne, R. (2005). Cell surface recycling of internalized antigen permits dendritic cell priming of B cells. Immunity, 23(5), 503-514.
    連結：
14. Bermudez, B., Lopez, S., Ortega, A., Varela, L. M., Pacheco, Y. M., Abia, R., et al. (2011). Oleic acid in olive oil: from a metabolic framework toward a clinical perspective. Current Pharmaceutical Design, 17(8), 831-843.
    連結：
15. Bielecka, M., Biedrzycka, E., Majkowska, A., Juskiewicz, J., & Wroblewska, M. (2002). Effect of non-digestible oligosaccharides on gut microecosystem in rats. Food Research International, 35(2-3), 139-144.
    連結：
16. Bischoff, S. C., & Kramer, S. (2007). Human mast cells, bacteria, and intestinal immunity. Immunological Reviews, 217, 329-337.
    連結：
17. Bjorksten, B. (1999). The environmental influence on childhood asthma. Allergy, 54 Suppl 49, 17-23.
    連結：
18. Bloemen, J. G., Venema, K., de Poll, M. C. V., Damink, S. W. O., Buurman, W. A., & Dejong, C. H. (2009). Short chain fatty acids exchange across the gut and liver in humans measured at surgery. Clinical Nutrition, 28(6), 657-661.
    連結：
19. Bluestone, J. A., & Abbas, A. K. (2003). Natural versus adaptive regulatory T cells. Nature Reviews Immunology, 3(3), 253-257.
    連結：
20. Bogunovic, M., Mortha, A., Muller, P. A., & Merad, M. (2012). Mononuclear phagocyte diversity in the intestine. Immunologic Research, 54(1-3), 37-49.
    連結：
21. Bopp, T., Becker, C., Klein, M., Klein-Hessling, S., Palmetshofer, A., Serfling, E., et al. (2007). Cyclic adenosine monophosphate is a key component of regulatory T cell mediated suppression. Journal of Experimental Medicine, 204(6), 1303-1310.
    連結：
22. Borsutzky, S., Cazac, B. B., Roes, J., & Guzman, C. A. (2004). TGF-beta receptor signaling is critical for mucosal IgA responses. Journal of Immunology, 173(5), 3305-3309.
    連結：
23. Brand, S. (2009). Crohn's disease: Th1, Th17 or both? The change of a paradigm: new immunological and genetic insights implicate Th17 cells in the pathogenesis of Crohn's disease. Gut, 58(8), 1152-1167.
    連結：
24. Brandl, K., Plitas, G., Mihu, C. N., Ubeda, C., Jia, T., Fleisher, M., et al. (2008). Vancomycin-resistant enterococci exploit antibiotic-induced innate immune deficits. Nature, 455(7214), 804-807.
    連結：
25. Brown, E. M., Sadarangani, M., & Finlay, B. B. (2013). The role of the immune system in governing host-microbe interactions in the intestine. Nature immunology, 14(7), 660-667.
    連結：
26. Calder, P. C. (2015a). Functional roles of fatty acids and their effects on human health. Journal of Parenteral and Enteral Nutrition, 39, 18s-32s.
    連結：
27. Calder, P. C. (2015b). Marine omega-3 fatty acids and inflammatory processes: Effects, mechanisms and clinical relevance. Biochimica Et Biophysica Acta-Molecular and Cell Biology of Lipids, 1851(4), 469-484.
    連結：
28. Cani, P. D., Bibiloni, R., Knauf, C., Neyrinck, A. M., Neyrinck, A. M., Delzenne, N. M., et al. (2008). Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes, 57(6), 1470-1481.
    連結：
29. Cani, P. D., Possemiers, S., Van de Wiele, T., Guiot, Y., Everard, A., Rottier, O., et al. (2009). Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut, 58(8), 1091-1103.
    連結：
30. Castillo, N. A., Perdigon, G., & de Moreno de Leblanc, A. (2011). Oral administration of a probiotic Lactobacillus modulates cytokine production and TLR expression improving the immune response against Salmonella enterica serovar Typhimurium infection in mice. BMC Microbiology, 11, 177.
    連結：
31. Chan, L. S., Robinson, N., & Xu, L. (2001). Expression of interleukin-4 in the epidermis of transgenic mice results in a pruritic inflammatory skin disease: an experimental animal model to study atopic dermatitis. Journal of Investigative Dermatology, 117(4), 977-983.
    連結：
32. Chang, A., Robison, R., Cai, M., & Singh, A. M. (2016). Natural History of Food-Triggered Atopic Dermatitis and Development of Immediate Reactions in Children. Journal of Allergy and Clinical Immunology-in Practice, 4(2), 229-236.
    連結：
33. Chawla, R., & Patil, G. R. (2010). Soluble dietary fiber. Comprehensive Reviews in Food Science and Food Safety, 9(2), 178-196.
    連結：
34. Clemente, J. C., Ursell, L. K., Parfrey, L. W., & Knight, R. (2012). The impact of the gut microbiota on human health: an integrative view. Cell, 148(6), 1258-1270.
    連結：
35. Collison, L. W., Workman, C. J., Kuo, T. T., Boyd, K., Wang, Y., Vignali, K. M., et al. (2007). The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature, 450(7169), 566-569.
    連結：
36. Cookson, W. O., & Moffatt, M. F. (2002). The genetics of atopic dermatitis. Current Opinion in Allergy and Clinical Immunology, 2(5), 383-387.
    連結：
37. Cox, M. A., Jackson, J., Stanton, M., Rojas-Triana, A., Bober, L., Laverty, M., et al. (2009). Short-chain fatty acids act as antiinflammatory mediators by regulating prostaglandin E-2 and cytokines. World Journal of Gastroenterology, 15(44), 5549-5557.
    連結：
38. Craig, S. W., & Cebra, J. J. (1971). Peyer's patches: an enriched source of precursors for IgA-producing immunocytes in the rabbit. Journal of Experimental Medicine, 134(1), 188-200.
    連結：
39. Deaglio, S., Dwyer, K. M., Gao, W., Friedman, D., Usheva, A., Erat, A., et al. (2007). Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. Journal of Experimental Medicine, 204(6), 1257-1265.
    連結：
40. Delarue, J., & Magnan, C. (2007). Free fatty acids and insulin resistance. Current Opinion in Clinical Nutrition & Metabolic Care, 10(2), 142-148.
    連結：
41. Di Giacinto, C., Marinaro, M., Sanchez, M., Strober, W., & Boirivant, M. (2005). Probiotics ameliorate recurrent Th1-mediated murine colitis by inducing IL-10 and IL-10-dependent TGF-beta-bearing regulatory cells. Journal of Immunology, 174(6), 3237-3246.
    連結：
42. Djaldetti, M., & Bessler, H. (2017). Probiotic strains modulate cytokine production and the immune interplay between human peripheral blood mononucear cells and colon cancer cells. Fems Microbiology Letters, 364(3).
    連結：
43. Doucette, C. R., Horowitz, M. C., Berry, R., MacDougald, O. A., Anunciado-Koza, R., Koza, R. A., et al. (2015). A High Fat Diet Increases Bone Marrow Adipose Tissue (MAT) But Does Not Alter Trabecular or Cortical Bone Mass in C57BL/6J Mice. Journal of Cellular Physiology, 230(9), 2032-2037.
    連結：
44. Dumas, M. E., Barton, R. H., Toye, A., Cloarec, O., Blancher, C., Rothwell, A., et al. (2006). Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice. Proceedings of the National Academy of Sciences of the United States of America, 103(33), 12511-12516.
    連結：
45. Elia, M., & Cummings, J. H. (2007). Physiological aspects of energy metabolism and gastrointestinal effects of carbohydrates. European Journal of Clinical Nutrition, 61 Suppl 1, S40-74.
    連結：
46. Ellwood, P., Asher, M. I., Bjorksten, B., Burr, M., Pearce, N., & Robertson, C. F. (2001). Diet and asthma, allergic rhinoconjunctivitis and atopic eczema symptom prevalence: an ecological analysis of the International Study of Asthma and Allergies in Childhood (ISAAC) data. ISAAC Phase One Study Group. European Respiratory Journal, 17(3), 436-643.
    連結：
47. Erkkila, A., de Mello, V. D., Riserus, U., & Laaksonen, D. E. (2008). Dietary fatty acids and cardiovascular disease: an epidemiological approach. Progress in Lipid Research, 47(3), 172-187.
    連結：
48. Esser, D., van Dijk, S. J., Oosterink, E., Lopez, S., Muller, M., & Afman, L. A. (2015). High fat challenges with different fatty acids affect distinct atherogenic gene expression pathways in immune cells from lean and obese subjects. Molecular Nutrition & Food Research, 59(8), 1563-1572.
    連結：
49. Eswaran, S., Muir, J., & Chey, W. D. (2013). Fiber and functional gastrointestinal disorders. American Journal of Gastroenterology, 108(5), 718-727.
    連結：
50. Fallarino, F., Grohmann, U., Hwang, K. W., Orabona, C., Vacca, C., Bianchi, R., et al. (2003). Modulation of tryptophan catabolism by regulatory T cells. Nature immunology, 4(12), 1206-1212.
    連結：
51. Ferrucci, L., Cherubini, A., Bandinelli, S., Bartali, B., Corsi, A., Lauretani, F., et al. (2006). Relationship of plasma polyunsaturated fatty acids to circulating inflammatory markers. The Journal of Clinical Endocrinology & Metabolism, 91(2), 439-446.
    連結：
52. Finch, J., Munhutu, M. N., & Whitaker-Worth, D. L. (2010). Atopic dermatitis and nutrition. Clinics in Dermatology, 28(6), 605-614.
    連結：
53. Flint, H. J., Bayer, E. A., Rincon, M. T., Lamed, R., & White, B. A. (2008). Polysaccharide utilization by gut bacteria: potential for new insights from genomic analysis. Nature Reviews Microbiology, 6(2), 121-131.
    連結：
54. Flint, H. J., Scott, K. P., Duncan, S. H., Louis, P., & Forano, E. (2012). Microbial degradation of complex carbohydrates in the gut. Gut Microbes, 3(4), 289-306.
    連結：
55. Forouhi, N. G., Koulman, A., Sharp, S. J., Imamura, F., Kroger, J., Schulze, M. B., et al. (2014). Differences in the prospective association between individual plasma phospholipid saturated fatty acids and incident type 2 diabetes: the EPIC-InterAct case-cohort study. Lancet Diabetes & Endocrinology, 2(10), 810-818.
    連結：
56. Furusawa, Y., Obata, Y., Fukuda, S., Endo, T. A., Nakato, G., Takahashi, D., et al. (2013). Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature, 504(7480), 446-450.
    連結：
57. Garrett, W. S., Gallini, C. A., Yatsunenko, T., Michaud, M., DuBois, A., Delaney, M. L., et al. (2010). Enterobacteriaceae act in concert with the gut microbiota to induce spontaneous and maternally transmitted colitis. Cell Host & Microbe, 8(3), 292-300.
    連結：
58. Gdalevich, M., Mimouni, D., David, M., & Mimouni, M. (2001). Breast-feeding and the onset of atopic dermatitis in childhood: a systematic review and meta-analysis of prospective studies. Journal of the American Academy of Dermatology, 45(4), 520-527.
    連結：
59. Geleijnse, J. M., Giltay, E. J., Grobbee, D. E., Donders, A. R., & Kok, F. J. (2002). Blood pressure response to fish oil supplementation: metaregression analysis of randomized trials. Journal of Hypertension, 20(8), 1493-1499.
    連結：
60. Goldman, A. S. (2007). The immune system in human milk and the developing infant. Breastfeeding Medicine, 2(4), 195-204.
    連結：
61. Gondek, D. C., Lu, L. F., Quezada, S. A., Sakaguchi, S., & Noelle, R. J. (2005). Cutting edge: contact-mediated suppression by CD4+CD25+ regulatory cells involves a granzyme B-dependent, perforin-independent mechanism. Journal of Immunology, 174(4), 1783-1786.
    連結：
62. Gong, Y., Liu, L., He, X., Zhao, H., Yang, J., Li, L., et al. (2015). The th17/treg immune balance in ulcerative colitis patients with two different chinese syndromes: dampness-heat in large intestine and spleen and kidney yang deficiency syndrome. Evidence-Based Complementary and Alternative Medicine, 2015, 264317.
    連結：
63. Green, E. A., Gorelik, L., McGregor, C. M., Tran, E. H., & Flavell, R. A. (2003). CD4+CD25+ T regulatory cells control anti-islet CD8+ T cells through TGF-beta-TGF-beta receptor interactions in type 1 diabetes. Proceedings of the National Academy of Sciences of the United States of America, 100(19), 10878-10883.
    連結：
64. Gregor, M. F., & Hotamisligil, G. S. (2011). Inflammatory mechanisms in obesity. Annual Review of Immunology, 29, 415-445.
    連結：
65. Guilliams, M., Crozat, K., Henri, S., Tamoutounour, S., Grenot, P., Devilard, E., et al. (2010). Skin-draining lymph nodes contain dermis-derived CD103(-) dendritic cells that constitutively produce retinoic acid and induce Foxp3(+) regulatory T cells. Blood, 115(10), 1958-1968.
    連結：
66. Hacini-Rachinel, F., Nancey, S., Boschetti, G., Sardi, F., Doucet-Ladeveze, R., Durand, P. Y., et al. (2009). CD4+ T cells and Lactobacillus casei control relapsing colitis mediated by CD8+ T cells. Journal of Immunology, 183(9), 5477-5486.
    連結：
67. Haghikia, A., Jorg, S., Duscha, A., Berg, J., Manzel, A., Waschbisch, A., et al. (2015). Dietary fatty acids directly impact central nervous system autoimmunity via the small intestine. Immunity, 43(4), 817-829.
    連結：
68. Hamilton, M. K., Ronveaux, C. C., Rust, B. M., Newman, J. W., Hawley, M., Barile, D., et al. (2017). Prebiotic milk oligosaccharides prevent development of obese phenotype, impairment of gut permeability, and microbial dysbiosis in high fat-fed mice. American Journal of Physiology-Gastrointestinal and Liver Physiology, 312(5), G474-G487.
    連結：
69. Heath, W. R., & Carbone, F. R. (2009). Dendritic cell subsets in primary and secondary T cell responses at body surfaces. Nature immunology, 10(12), 1237-1244.
    連結：
70. Higashimura, Y., Naito, Y., Takagi, T., Mizushima, K., Hirai, Y., Harusato, A., et al. (2013). Oligosaccharides from agar inhibit murine intestinal inflammation through the induction of heme oxygenase-1 expression. Journal of Gastroenterology, 48(8), 897-909.
    連結：
71. Higashimura, Y., Naito, Y., Takagi, T., Tanimura, Y., Mizushima, K., Harusato, A., et al. (2014). Preventive effect of agaro-oligosaccharides on non-steroidal anti-inflammatory drug-induced small intestinal injury in mice. Journal of Gastroenterology and Hepatology, 29(2), 310-317.
    連結：
72. Higashimura, Y., Naito, Y., Takagi, T., Uchiyama, K., Mizushima, K., Ushiroda, C., et al. (2016). Protective effect of agaro-oligosaccharides on gut dysbiosis and colon tumorigenesis in high-fat diet-fed mice. The American Journal of Physiology-Gastrointestinal and Liver Physiology, 310(6), G367-375.
    連結：
73. Homann, N. (2001). Alcohol and upper gastrointestinal tract cancer: the role of local acetaldehyde production. Addiction Biology, 6(4), 309-323.
    連結：
74. Hooper, L. V., & Gordon, J. I. (2001). Commensal host-bacterial relationships in the gut. Science, 292(5519), 1115-1118.
    連結：
75. Hooper, L. V., & Macpherson, A. J. (2010). Immune adaptations that maintain homeostasis with the intestinal microbiota. Nature Reviews Immunology, 10(3), 159-169.
    連結：
76. Hoppu, U., Rinne, M., Lampi, A. M., & Isolauri, E. (2005). Breast milk fatty acid composition is associated with development of atopic dermatitis in the infant. Journal of Pediatric Gastroenterology and Nutrition, 41(3), 335-338.
    連結：
77. Hu, F. B., Stampfer, M. J., Manson, J. E., Ascherio, A., Colditz, G. A., Speizer, F. E., et al. (1999). Dietary saturated fats and their food sources in relation to the risk of coronary heart disease in women. American Journal of Clinical Nutrition, 70(6), 1001-1008.
    連結：
78. Huang, W. C., Tsai, T. H., Chuang, L. T., Li, Y. Y., Zouboulis, C. C., & Tsai, P. J. (2014). Anti-bacterial and anti-inflammatory properties of capric acid against Propionibacterium acnes: a comparative study with lauric acid. Journal of Dermatological Science, 73(3), 232-240.
    連結：
79. Innis, S. M. (2014). Impact of maternal diet on human milk composition and neurological development of infants. The American journal of clinical nutrition, 99(3), 734S-741S.
    連結：
80. Insull, W., Jr., Hirsch, J., James, T., & Ahrens, E. H., Jr. (1959). The fatty acids of human milk. II. Alterations produced by manipulation of caloric balance and exchange of dietary fats. Journal of Clinical Investigation, 38(2), 443-450.
    連結：
81. Isolauri, E., Arvola, T., Sutas, Y., Moilanen, E., & Salminen, S. (2000). Probiotics in the management of atopic eczema. Clinical & Experimental Allergy, 30(11), 1604-1610.
    連結：
82. Ivanov, II, Atarashi, K., Manel, N., Brodie, E. L., Shima, T., Karaoz, U., et al. (2009). Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell, 139(3), 485-498.
    連結：
83. Iwasaki, A., & Kelsall, B. L. (1999). Freshly isolated Peyer's patch, but not spleen, dendritic cells produce interleukin 10 and induce the differentiation of T helper type 2 cells. Journal of Experimental Medicine, 190(2), 229-239.
    連結：
84. Joetham, A., Takeda, K., Taube, C., Miyahara, N., Matsubara, S., Koya, T., et al. (2007). Naturally occurring lung CD4(+)CD25(+) T cell regulation of airway allergic responses depends on IL-10 induction of TGF-beta. Journal of Immunology, 178(3), 1433-1442.
    連結：
85. Jung, C., Hugot, J. P., & Barreau, F. (2010). Peyer's Patches: The Immune Sensors of the Intestine. International Journal of Inflammation.
    連結：
86. Jung, T., & Stingl, G. (2008). Atopic dermatitis: therapeutic concepts evolving from new pathophysiologic insights. Journal of Allergy and Clinical Immunology, 122(6), 1074-1081.
    連結：
87. Jungersen, M., Wind, A., Johansen, E., Christensen, J. E., Stuer-Lauridsen, B., & Eskesen, D. (2014). The Science behind the Probiotic Strain Bifidobacterium animalis subsp. lactis BB-12((R)). Microorganisms, 2(2), 92-110.
    連結：
88. Kalliomaki, M., Collado, M. C., Salminen, S., & Isolauri, E. (2008). Early differences in fecal microbiota composition in children may predict overweight. American Journal of Clinical Nutrition, 87(3), 534-538.
    連結：
89. Kankaanpaa, P., Nurmela, K., Erkkila, A., Kalliomaki, M., Holmberg-Marttila, D., Salminen, S., et al. (2001). Polyunsaturated fatty acids in maternal diet, breast milk, and serum lipid fatty acids of infants in relation to atopy. Allergy, 56(7), 633-638.
    連結：
90. Kawamoto, S., Maruya, M., Kato, L. M., Suda, W., Atarashi, K., Doi, Y., et al. (2014). Foxp3(+) T cells regulate immunoglobulin a selection and facilitate diversification of bacterial species responsible for immune homeostasis. Immunity, 41(1), 152-165.
    連結：
91. Kim, Choi, M. S., & Han, S. N. (2011). High fat diet-induced obesity leads to proinflammatory response associated with higher expression of NOD2 protein. Nutrition Research and Practice, 5(3), 219-223.
    連結：
92. Kim, & Ho, S. B. (2010). Intestinal goblet cells and mucins in health and disease: recent insights and progress. Current Gastroenterology Reports, 12(5), 319-330.
    連結：
93. Kim, M., Qie, Y., Park, J., & Kim, C. H. (2016). Gut microbial metabolites fuel host antibody responses. Cell Host & Microbe, 20(2), 202-214.
    連結：
94. Klein-Platat, C., Drai, J., Oujaa, M., Schlienger, J. L., & Simon, C. (2005). Plasma fatty acid composition is associated with the metabolic syndrome and low-grade inflammation in overweight adolescents. American Journal of Clinical Nutrition, 82(6), 1178-1184.
    連結：
95. Knip, M., & Siljander, H. (2016). The role of the intestinal microbiota in type 1 diabetes mellitus. Nature Reviews Endocrinology, 12(3), 154-167.
    連結：
96. Koch, C., Dolle, S., Metzger, M., Rasche, C., Jungclas, H., Ruhl, R., et al. (2008). Docosahexaenoic acid (DHA) supplementation in atopic eczema: a randomized, double-blind, controlled trial. British Journal of Dermatology, 158(4), 786-792.
    連結：
97. Kohm, A. P., Carpentier, P. A., Anger, H. A., & Miller, S. D. (2002). Cutting edge: CD4+CD25+ regulatory T cells suppress antigen-specific autoreactive immune responses and central nervous system inflammation during active experimental autoimmune encephalomyelitis. Journal of Immunology, 169(9), 4712-4716.
    連結：
98. Koutrolos, M., Berer, K., Kawakami, N., Wekerle, H., & Krishnamoorthy, G. (2014). Treg cells mediate recovery from EAE by controlling effector T cell proliferation and motility in the CNS. Acta Neuropathologica Communications, 2, 163.
    連結：
99. Kramer, M. S., Guo, T., Platt, R. W., Shapiro, S., Collet, J. P., Chalmers, B., et al. (2002). Breastfeeding and infant growth: biology or bias? Pediatrics, 110(2), 343-347.
    連結：
100. Kunz, B., Oranje, A. P., Labreze, L., Stalder, J. F., Ring, J., & Taieb, A. (1997). Clinical validation and guidelines for the SCORAD index: consensus report of the European Task Force on Atopic Dermatitis. Dermatology, 195(1), 10-19.
     連結：
101. Lahl, K., Loddenkemper, C., Drouin, C., Freyer, J., Arnason, J., Eberl, G., et al. (2007). Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease. Journal of Experimental Medicine, 204(1), 57-63.
     連結：
102. Lan, R. Y., Ansari, A. A., Lian, Z. X., & Gershwin, M. E. (2005). Regulatory T cells: Development, function and role in autoimmunity. Autoimmunity Reviews, 4(6), 351-363.
     連結：
103. Larrosa, M., Luceri, C., Vivoli, E., Pagliuca, C., Lodovici, M., Moneti, G., et al. (2009). Polyphenol metabolites from colonic microbiota exert anti-inflammatory activity on different inflammation models. Molecular Nutrition & Food Research, 53(8), 1044-1054.
     連結：
104. Le Leu, R. K., Brown, I. L., Hu, Y., Bird, A. R., Jackson, M., Esterman, A., et al. (2005). A synbiotic combination of resistant starch and Bifidobacterium lactis facilitates apoptotic deletion of carcinogen-damaged cells in rat colon. The Journal of nutrition, 135(5), 996-1001.
     連結：
105. Le Poul, E., Loison, C., Struyf, S., Springael, J. Y., Lannoy, V., Decobecq, M. E., et al. (2003). Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. Journal of Biological Chemistry, 278(28), 25481-25489.
     連結：
106. Lee, J., Seto, D., & Bielory, L. (2008). Meta-analysis of clinical trials of probiotics for prevention and treatment of pediatric atopic dermatitis. Journal of Allergy and Clinical Immunology, 121(1), 116-121.
     連結：
107. Lee, J. Y., Plakidas, A., Lee, W. H., Heikkinen, A., Chanmugam, P., Bray, G., et al. (2003). Differential modulation of Toll-like receptors by fatty acids: preferential inhibition by n-3 polyunsaturated fatty acids. Journal of Lipid Research, 44(3), 479-486.
     連結：
108. Lee, J. Y., Sohn, K. H., Rhee, S. H., & Hwang, D. (2001). Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4. Journal of Biological Chemistry, 276(20), 16683-16689.
     連結：
109. Lee, Y., Ba, Z., Roberts, R. F., Rogers, C. J., Fleming, J. A., Meng, H., et al. (2017). Effects of Bifidobacterium animalis subsp. lactis BB-12(R) on the lipid/lipoprotein profile and short chain fatty acids in healthy young adults: a randomized controlled trial. Nutrition Journal, 16(1), 39.
     連結：
110. Lewkowich, I. P., Herman, N. S., Schleifer, K. W., Dance, M. P., Chen, B. L., Dienger, K. M., et al. (2005). CD4(+) CD25(+) T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function. Journal of Experimental Medicine, 202(11), 1549-1561.
     連結：
111. Ley, R. E., Turnbaugh, P. J., Klein, S., & Gordon, J. I. (2006). Microbial ecology: human gut microbes associated with obesity. Nature, 444(7122), 1022-1023.
     連結：
112. Liong, M. T., & Shah, N. P. (2005). Optimization of cholesterol removal, growth and fermentation patterns of Lactobacillus acidophilus ATCC 4962 in the presence of mannitol, fructo‐oligosaccharide and inulin: a response surface methodology approach. Journal of applied microbiology, 98(5), 1115-1126.
     連結：
113. Louis, N. A., & Lin, P. W. (2009). The intestinal immune barrier. NeoReviews, 10(4), e180-e190.
     連結：
114. Lu, Y., Fan, C., Li, P., Lu, Y., Chang, X., & Qi, K. (2016). Short Chain Fatty Acids Prevent High-fat-diet-induced Obesity in Mice by Regulating G Protein-coupled Receptors and Gut Microbiota. Scientific Reports, 6, 37589.
     連結：
115. Lu, Y. Y., Fan, C. N., Li, P., Lu, Y. F., Chang, X. L., & Qi, K. M. (2016). Short chain fatty acids prevent high-fat-diet-induced obesity in mice by regulating G protein-coupled receptors and gut microbiota. Scientific Reports, 6.
     連結：
116. Macpherson, A. J., & Slack, E. (2007). The functional interactions of commensal bacteria with intestinal secretory IgA. Current Opinion in Gastroenterology, 23(6), 673-678.
     連結：
117. Macpherson, A. J., & Smith, K. (2006). Mesenteric lymph nodes at the center of immune anatomy. Journal of Experimental Medicine, 203(3), 497-500.
     連結：
118. Macpherson, A. J., & Uhr, T. (2004). Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science, 303(5664), 1662-1665.
     連結：
119. Marson, A., Kretschmer, K., Frampton, G. M., Jacobsen, E. S., Polansky, J. K., Maclsaac, K. D., et al. (2007). Foxp3 occupancy and regulation of key target genes during T-cell stimulation. Nature, 445(7130), 931-935.
     連結：
120. Maslowski, K. M., Vieira, A. T., Ng, A., Kranich, J., Sierro, F., Yu, D., et al. (2009). Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature, 461(7268), 1282-1286.
     連結：
121. Maynard, C. L., Harrington, L. E., Janowski, K. M., Oliver, J. R., Zindl, C. L., Rudensky, A. Y., et al. (2007). Regulatory T cells expressing interleukin 10 develop from Foxp3+ and Foxp3- precursor cells in the absence of interleukin 10. Nature immunology, 8(9), 931-941.
     連結：
122. Mazmanian, S. K., Liu, C. H., Tzianabos, A. O., & Kasper, D. L. (2005). An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell, 122(1), 107-118.
     連結：
123. Mazmanian, S. K., Round, J. L., & Kasper, D. L. (2008). A microbial symbiosis factor prevents intestinal inflammatory disease. Nature, 453(7195), 620-625.
     連結：
124. McGeachy, M. J., Stephens, L. A., & Anderton, S. M. (2005). Natural recovery and protection from autoimmune encephalomyelitis: contribution of CD4+CD25+ regulatory cells within the central nervous system. Journal of Immunology, 175(5), 3025-3032.
     連結：
125. McGuckin, M. A., Eri, R., Simms, L. A., Florin, T. H. J., & Radford-Smith, G. (2009). Intestinal Barrier Dysfunction in Inflammatory Bowel Diseases. Inflammatory Bowel Diseases, 15(1), 100-113.
     連結：
126. Mensink, R. P., Zock, P. L., Kester, A. D., & Katan, M. B. (2003). Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. The American journal of clinical nutrition, 77(5), 1146-1155.
     連結：
127. Miyake, Y., Sasaki, S., Tanaka, K., Ohfuji, S., & Hirota, Y. (2009). Maternal fat consumption during pregnancy and risk of wheeze and eczema in Japanese infants aged 16-24 months: the Osaka Maternal and Child Health Study. Thorax, 64(9), 815-821.
     連結：
128. Mora, J. R., Iwata, M., Eksteen, B., Song, S. Y., Junt, T., Senman, B., et al. (2006). Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells. Science, 314(5802), 1157-1160.
     連結：
129. Moreyra, A. E., Wilson, A. C., & Koraym, A. (2005). Effect of combining psyllium fiber with simvastatin in lowering cholesterol. Archives of Internal Medicine, 165(10), 1161-1166.
     連結：
130. Mucida, D., Park, Y., Kim, G., Turovskaya, O., Scott, I., Kronenberg, M., et al. (2007a). Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science, 317(5835), 256-260.
     連結：
131. Mucida, D., Park, Y., Kim, G., Turovskaya, O., Scott, I., Kronenberg, M., et al. (2007b). Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science, 317(5835), 256-260.
     連結：
132. Murphy, E. F., Cotter, P. D., Healy, S., Marques, T. M., O'Sullivan, O., Fouhy, F., et al. (2010). Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models. Gut, 59(12), 1635-1642.
     連結：
133. Mussatto, S. I., & Mancilha, I. M. (2007). Non-digestible oligosaccharides: A review. Carbohydrate Polymers, 68(3), 587-597.
     連結：
134. Nemets, B., Stahl, Z., & Belmaker, R. H. (2002). Addition of omega-3 fatty acid to maintenance medication treatment for recurrent unipolar depressive disorder. The American Journal of Psychiatry, 159(3), 477-479.
     連結：
135. Newson, R. B., Shaheen, S. O., Henderson, A. J., Emmett, P. M., Sherriff, A., & Calder, P. C. (2004). Umbilical cord and maternal blood red cell fatty acids and early childhood wheezing and eczema. Journal of Allergy and Clinical Immunology, 114(3), 531-537.
     連結：
136. Nishikawa, S., Yasoshima, A., Doi, K., Nakayama, H., & Uetsuka, K. (2007). Involvement of sex, strain and age factors in high fat diet-induced obesity in C57BL6J and BALB/cA mice. Experimental Animals, 56(4), 263-272.
     連結：
137. Nolting, J., Daniel, C., Reuter, S., Stuelten, C., Li, P., Sucov, H., et al. (2009). Retinoic acid can enhance conversion of naive into regulatory T cells independently of secreted cytokines. Journal of Experimental Medicine, 206(10), 2131-2139.
     連結：
138. Nutten, S. (2015). Atopic dermatitis: global epidemiology and risk factors. Annals of Nutrition and Metabolism, 66, 8-16.
     連結：
139. O'Hara, A. M., & Shanahan, F. (2006). The gut flora as a forgotten organ. Embo Reports, 7(7), 688-693.
     連結：
140. O'Mahony, C., Scully, P., O'Mahony, D., Murphy, S., O'Brien, F., Lyons, A., et al. (2008). Commensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-kappaB activation. PLOS Pathogens, 4(8), e1000112.
     連結：
141. Oien, T., Storro, O., & Johnsen, R. (2010). Do early intake of fish and fish oil protect against eczema and doctor-diagnosed asthma at 2 years of age? A cohort study. Journal of Epidemiology and Community Health, 64(2), 124-129.
     連結：
142. Olszak, T., An, D. D., Zeissig, S., Vera, M. P., Richter, J., Franke, A., et al. (2012). Microbial Exposure During Early Life Has Persistent Effects on Natural Killer T Cell Function. Science, 336(6080), 489-493.
     連結：
143. Ostman, S., Rask, C., Wold, A. E., Hultkrantz, S., & Telemo, E. (2006). Impaired regulatory T cell function in germ-free mice. European Journal of Immunology, 36(9), 2336-2346.
     連結：
144. Ott, S. J., Musfeldt, M., Wenderoth, D. F., Hampe, J., Brant, O., Folsch, U. R., et al. (2004). Reduction in diversity of the colonic mucosa associated bacterial microflora in patients with active inflammatory bowel disease. Gut, 53(5), 685-693.
     連結：
145. Owen, C. G., Martin, R. M., Whincup, P. H., Smith, G. D., & Cook, D. G. (2005). Effect of infant feeding on the risk of obesity across the life course: a quantitative review of published evidence. Pediatrics, 115(5), 1367-1377.
     連結：
146. Palm, N. W., de Zoete, M. R., Cullen, T. W., Barry, N. A., Stefanowski, J., Hao, L., et al. (2014). Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease. Cell, 158(5), 1000-1010.
     連結：
147. Pan, X. D., Chen, F. Q., Wu, T. X., Tang, H. G., & Zhao, Z. Y. (2009). Prebiotic oligosaccharides change the concentrations of short-chain fatty acids and the microbial population of mouse bowel. Journal of Zhejiang University SCIENCE B, 10(4), 258-263.
     連結：
148. Pandiyan, P., Zheng, L., Ishihara, S., Reed, J., & Lenardo, M. J. (2007). CD4+CD25+Foxp3+ regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+ T cells. Nature immunology, 8(12), 1353-1362.
     連結：
149. Persson, E. K., Scott, C. L., Mowat, A. M., & Agace, W. W. (2013). Dendritic cell subsets in the intestinal lamina propria: Ontogeny and function. European Journal of Immunology, 43(12), 3098-3107.
     連結：
150. Pesonen, M., Kallio, M. J. T., Ranki, A., & Siimes, M. A. (2006). Prolonged exclusive breastfeeding is associated with increased atopic dermatitis: a prospective follow-up study of unselected healthy newborns from birth to age 20 years. Clinical and Experimental Allergy, 36(8), 1011-1018.
     連結：
151. Rabionet, M., Gorgas, K., & Sandhoff, R. (2014). Ceramide synthesis in the epidermis. Biochimica et Biophysica Acta, 1841(3), 422-434.
     連結：
152. Ramsden, C. E., Hibbeln, J. R., Majchrzak, S. F., & Davis, J. M. (2010). n-6 Fatty acid-specific and mixed polyunsaturate dietary interventions have different effects on CHD risk: a meta-analysis of randomised controlled trials. British Journal of Nutrition, 104(11), 1586-1600.
     連結：
153. Reeves, P. G., Nielsen, F. H., & Fahey, G. C., Jr. (1993). 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. Journal of Nutrition, 123(11), 1939-1951.
     連結：
154. Reizis, B., Bunin, A., Ghosh, H. S., Lewis, K. L., & Sisirak, V. (2011). Plasmacytoid Dendritic Cells: Recent Progress and Open Questions. Annual Review of Immunology, 29, 163-183.
     連結：
155. Respondek, F., Gerard, P., Bossis, M., Boschat, L., Bruneau, A., Rabot, S., et al. (2013). Short-chain fructo-oligosaccharides modulate intestinal microbiota and metabolic parameters of humanized gnotobiotic diet induced obesity mice. PLoS One, 8(8), e71026.
     連結：
156. Ridlon, J. M., Kang, D. J., & Hylemon, P. B. (2006). Bile salt biotransformations by human intestinal bacteria. Journal of Lipid Research, 47(2), 241-259.
     連結：
157. Rocha, D. M., Bressan, J., & Hermsdorff, H. H. (2017). The role of dietary fatty acid intake in inflammatory gene expression: a critical review. Sao Paulo Medical Journal, 135(2), 157-168.
     連結：
158. Romieu, I., Torrent, M., Garcia-Esteban, R., Ferrer, C., Ribas-Fito, N., Anto, J. M., et al. (2007). Maternal fish intake during pregnancy and atopy and asthma in infancy. Clinical & Experimental Allergy, 37(4), 518-525.
     連結：
159. Rossi, M., Amaretti, A., & Raimondi, S. (2011). Folate production by probiotic bacteria. Nutrients, 3(1), 118-134.
     連結：
160. Round, J. L., Lee, S. M., Li, J., Tran, G., Jabri, B., Chatila, T. A., et al. (2011). The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota. Science, 332(6032), 974-977.
     連結：
161. Round, J. L., & Mazmanian, S. K. (2009). The gut microbiota shapes intestinal immune responses during health and disease. Nature Reviews Immunology, 9(5), 313-323.
     連結：
162. Rubtsov, Y. P., Rasmussen, J. P., Chi, E. Y., Fontenot, J., Castelli, L., Ye, X., et al. (2008). Regulatory T cell-derived interleukin-10 limits inflammation at environmental interfaces. Immunity, 28(4), 546-558.
     連結：
163. Sako, T., Matsumoto, K., & Tanaka, R. (1999). Recent progress on research and applications of non-digestible galacto-oligosaccharides. International Dairy Journal, 9(1), 69-80.
     連結：
164. Samur, G., Topcu, A., & Turan, S. (2009). Trans fatty acids and fatty acid composition of mature breast milk in turkish women and their association with maternal diet's. Lipids, 44(5), 405-413.
     連結：
165. Sato, A., Hashiguchi, M., Toda, E., Iwasaki, A., Hachimura, S., & Kaminogawa, S. (2003). CD11b(+) Peyer's patch dendritic cells secrete IL-6 and induce IgA secretion from naive B cells. Journal of Immunology, 171(7), 3684-3690.
     連結：
166. Sausenthaler, S., Koletzko, S., Schaaf, B., Lehmann, I., Borte, M., Herbarth, O., et al. (2007). Maternal diet during pregnancy in relation to eczema and allergic sensitization in the offspring at 2 y of age. The American journal of clinical nutrition, 85(2), 530-537.
     連結：
167. Schwiertz, A., Taras, D., Schafer, K., Beijer, S., Bos, N. A., Donus, C., et al. (2010). Microbiota and SCFA in lean and overweight healthy subjects. Obesity (Silver Spring), 18(1), 190-195.
     連結：
168. Schwingshackl, L., & Hoffmann, G. (2014). Monounsaturated fatty acids, olive oil and health status: a systematic review and meta-analysis of cohort studies. Lipids in Health and Disease, 13, 154.
     連結：
169. Shortman, K., & Heath, W. R. (2010). The CD8+dendritic cell subset. Immunological Reviews, 234, 18-31.
     連結：
170. Singh, N., Gurav, A., Sivaprakasam, S., Brady, E., Padia, R., Shi, H., et al. (2014). Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity, 40(1), 128-139.
     連結：
171. Siri-Tarino, P. W., Sun, Q., Hu, F. B., & Krauss, R. M. (2010). Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease. The American journal of clinical nutrition, 91(3), 535-546.
     連結：
172. Sleeth, M. L., Thompson, E. L., Ford, H. E., Zac-Varghese, S. E., & Frost, G. (2010). Free fatty acid receptor 2 and nutrient sensing: a proposed role for fibre, fermentable carbohydrates and short-chain fatty acids in appetite regulation. Nutrition Research Reviews, 23(1), 135-145.
     連結：
173. Snijders, B. E., Thijs, C., Dagnelie, P. C., Stelma, F. F., Mommers, M., Kummeling, I., et al. (2007). Breast-feeding duration and infant atopic manifestations, by maternal allergic status, in the first 2 years of life (KOALA study). Journal of Pediatrics, 151(4), 347-351.
     連結：
174. Song, H., Yoo, Y., Hwang, J., Na, Y. C., & Kim, H. S. (2016). Faecalibacterium prausnitzii subspecies-level dysbiosis in the human gut microbiome underlying atopic dermatitis. Journal of Allergy and Clinical Immunology, 137(3), 852-860.
     連結：
175. Spencer, J., Klavinskis, L. S., & Fraser, L. D. (2012). The human intestinal IgA response; burning questions. Frontiers in Immunology, 3, 108.
     連結：
176. Stary, G., Bangert, C., Stingl, G., & Kopp, T. (2005). Dendritic cells in atopic dermatitis: expression of FcepsilonRI on two distinct inflammation-associated subsets. International Archives of Allergy and Immunology, 138(4), 278-290.
     連結：
177. Stenman, L. K., Waget, A., Garret, C., Klopp, P., Burcelin, R., & Lahtinen, S. (2014). Potential probiotic Bifidobacterium animalis ssp. lactis 420 prevents weight gain and glucose intolerance in diet-induced obese mice. Beneficial Microbes, 5(4), 437-445.
     連結：
178. Stevens, L., Zhang, W., Peck, L., Kuczek, T., Grevstad, N., Mahon, A., et al. (2003). EFA supplementation in children with inattention, hyperactivity, and other disruptive behaviors. Lipids, 38(10), 1007-1021.
     連結：
179. Striz, I., Brabcova, E., Kolesar, L., & Sekerkova, A. (2014). Cytokine networking of innate immunity cells: a potential target of therapy. Clinical Science, 126(9), 593-612.
     連結：
180. Suarez-Varela, M. M., Garcia-Marcos Alvarez, L., Kogan, M. D., Gonzalez, A. L., Gimeno, A. M., Aguinaga Ontoso, I., et al. (2008). Climate and prevalence of atopic eczema in 6- to 7-year-old school children in Spain. ISAAC phase III. International Journal of Biometeorology, 52(8), 833-840.
     連結：
181. Sugahara, H., Odamaki, T., Hashikura, N., Abe, F., & Xiao, J. Z. (2015). Differences in folate production by bifidobacteria of different origins. Bioscience of Microbiota, Food and Health, 34(4), 87-93.
     連結：
182. Swedberg, K. (2011). n-3 fatty acids in cardiovascular disease. New England Journal of Medicine, 365(12), 1159-1159.
     連結：
183. Talham, G. L., Jiang, H. Q., Bos, N. A., & Cebra, J. J. (1999). Segmented filamentous bacteria are potent stimuli of a physiologically normal state of the murine gut mucosal immune system. Infection and Immunity, 67(4), 1992-2000.
     連結：
184. Tan, J., McKenzie, C., Vuillermin, P. J., Goverse, G., Vinuesa, C. G., Mebius, R. E., et al. (2016). Dietary fiber and bacterial SCFA enhance oral tolerance and protect against food allergy through diverse cellular pathways. Cell Reports, 15(12), 2809-2824.
     連結：
185. Thaiss, C. A., Zmora, N., Levy, M., & Elinav, E. (2016). The microbiome and innate immunity. Nature, 535(7610), 65-74.
     連結：
186. Tollefson, M. M., Bruckner, A. L., & Section On, D. (2014). Atopic dermatitis: skin-directed management. Pediatrics, 134(6), 1251-1258.
     連結：
187. Tomlin, J., & Read, N. W. (1988). Laxative properties of indigestible plastic particles. British Medical Journal, 297(6657), 1175-1176.
     連結：
188. Topping, D. L., & Clifton, P. M. (2001). Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiological Reviews, 81(3), 1031-1064.
     連結：
189. Treem, W. R., Ahsan, N., Kastoff, G., & Hyams, J. S. (1996). Fecal short-chain fatty acids in patients with diarrhea-predominant irritable bowel syndrome: In vitro studies of carbohydrate fermentation. Journal of Pediatric Gastroenterology and Nutrition, 23(3), 280-286.
     連結：
190. Tricon, S., Burdge, G. C., Kew, S., Banerjee, T., Russell, J. J., Jones, E. L., et al. (2004). Opposing effects of cis-9,trans-11 and trans-10,cis-12 conjugated linoleic acid on blood lipids in healthy humans. The American journal of clinical nutrition, 80(3), 614-620.
     連結：
191. Trompette, A., Gollwitzer, E. S., Yadava, K., Sichelstiel, A. K., Sprenger, N., Ngom-Bru, C., et al. (2014). Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nature Medicine, 20(2), 159-166.
     連結：
192. Tsoureli-Nikita, E., Hercogova, J., Lotti, T., & Menchini, G. (2002). Evaluation of dietary intake of vitamin E in the treatment of atopic dermatitis: a study of the clinical course and evaluation of the immunoglobulin E serum levels. International Journal of Dermatology, 41(3), 146-150.
     連結：
193. Turnbaugh, P. J., Baeckhed, F., Fulton, L., & Gordon, J. I. (2008). Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host & Microbe, 3(4), 213-223.
     連結：
194. Uhlig, H. H., Coombes, J., Mottet, C., Izcue, A., Thompson, C., Fanger, A., et al. (2006). Characterization of Foxp3+CD4+CD25+ and IL-10-secreting CD4+CD25+ T cells during cure of colitis. Journal of Immunology, 177(9), 5852-5860.
     連結：
195. van der Heijden, R. A., Sheedfar, F., Morrison, M. C., Hommelberg, P. P., Kor, D., Kloosterhuis, N. J., et al. (2015). High-fat diet induced obesity primes inflammation in adipose tissue prior to liver in C57BL/6j mice. Aging (Albany NY), 7(4), 256-268.
     連結：
196. Villalpando, S., & Lopez-Alarcon, M. (2000). Growth faltering is prevented by breast-feeding in underprivileged infants from Mexico City. Journal of Nutrition, 130(3), 546-552.
     連結：
197. Voon, P. T., Ng, T. K. W., Lee, V. K. M., & Nesaretnam, K. (2011). Diets high in palmitic acid (16:0), lauric and myristic acids (12:0+14:0), or oleic acid (18:1) do not alter postprandial or fasting plasma homocysteine and inflammatory markers in healthy Malaysian adults. American Journal of Clinical Nutrition, 94(6), 1451-1457.
     連結：
198. Walker, W. A., & Iyengar, R. S. (2015). Breast milk, microbiota, and intestinal immune homeostasis. Pediatric Research, 77(1-2), 220-228.
     連結：
199. Wang, Q., Imamura, F., Lemaitre, R. N., Rimm, E. B., Wang, M., King, I. B., et al. (2014). Plasma phospholipid trans-fatty acids levels, cardiovascular diseases, and total mortality: the cardiovascular health study. Journal of the American Heart Association, 3(4).
     連結：
200. Wang, Z., Klipfell, E., Bennett, B. J., Koeth, R., Levison, B. S., Dugar, B., et al. (2011). Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature, 472(7341), 57-63.
     連結：
201. Weiner, H. L. (2001). Induction and mechanism of action of transforming growth factor-beta-secreting Th3 regulatory cells. Immunological Reviews, 182, 207-214.
     連結：
202. Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., & Ferrante, A. W. (2003). Obesity is associated with macrophage accumulation in adipose tissue. Journal of Clinical Investigation, 112(12), 1796-1808.
     連結：
203. Wetzig, H., Schulz, R., Diez, U., Herbarth, O., Viehweg, B., & Borte, M. (2000). Associations between duration of breast-feeding, sensitization to hens' eggs and eczema infantum in one and two year old children at high risk of atopy. International Journal of Hygiene and Environmental Health, 203(1), 17-21.
     連結：
204. Wu, T. C., Lau, B. H., Chen, P. H., Wu, L. T., & Tang, R. B. (2010). Fatty acid composition of Taiwanese human milk. Journal of the Chinese Medical Association, 73(11), 581-588.
     連結：
205. Xu, W., Lan, Q., Chen, M., Chen, H., Zhu, N., Zhou, X., et al. (2012). Adoptive transfer of induced-Treg cells effectively attenuates murine airway allergic inflammation. PLoS One, 7(7), e40314.
     連結：
206. Yaqoob, P. (2002). Monounsaturated fatty acids and immune function. European Journal of Clinical Nutrition, 56 Suppl 3, S9-S13.
     連結：
207. Yin, Y. N., Yu, Q. F., Fu, N., Liu, X. W., & Lu, F. G. (2010). Effects of four Bifidobacteria on obesity in high-fat diet induced rats. The World Journal of Gastroenterology, 16(27), 3394-3401.
     連結：
208. Zelante, T., Iannitti, R. G., Cunha, C., De Luca, A., Giovannini, G., Pieraccini, G., et al. (2013). Tryptophan Catabolites from Microbiota Engage Aryl Hydrocarbon Receptor and Balance Mucosal Reactivity via Interleukin-22. Immunity, 39(2), 372-385.
     連結：
209. Zhang, C., Zhang, M., Pang, X., Zhao, Y., Wang, L., & Zhao, L. (2012). Structural resilience of the gut microbiota in adult mice under high-fat dietary perturbations. Multidisciplinary Journal of Microbial Ecology, 6(10), 1848-1857.
     連結：
210. Zhao, L. (2013). The gut microbiota and obesity: from correlation to causality. Nature Reviews Microbiology, 11(9), 639-647.
     連結：
211. Zhu, J., & Paul, W. E. (2008). CD4 T cells: fates, functions, and faults. Blood, 112(5), 1557-1569.
     連結：
212. 沈蓓婷 (2016)，母乳維生素A和D含量與異位性皮膚炎關聯性之探討
213. Castigli, E., Wilson, S. A., Scott, S., Dedeoglu, F., Xu, S., Lam, K. P., et al. (2005). TACI and BAFF-R mediate isotype switching in B cells. Journal of Experimental Medicine, 201(1), 35-39.
214. Cho, E. J., Rahman, M. A., Kim, S. W., Baek, Y. M., Hwang, H. J., Oh, J. Y., et al. (2008). Chitosan oligosaccharides inhibit adipogenesis in 3T3-L1 adipocytes. Journal of Microbiology and Biotechnology, 18(1), 80-87.
215. Cummings, J. H., Macfarlane, G. T., & Englyst, H. N. (2001). Prebiotic digestion and fermentation. The American journal of clinical nutrition, 73(2 Suppl), 415S-420S.
216. Erdman, S. E., Rao, V. P., Poutahidis, T., Ihrig, M. M., Ge, Z., Feng, Y., et al. (2003). CD4(+)CD25(+) regulatory lymphocytes require interleukin 10 to interrupt colon carcinogenesis in mice. Cancer Research, 63(18), 6042-6050.
217. Gill, C. I., & Rowland, I. R. (2002). Diet and cancer: assessing the risk. British Journal of Nutrition, 88 Suppl 1, S73-87.
218. Hoppu, U., Rinne, M., Salo-Vaananen, P., Lampi, A. M., Piironen, V., & Isolauri, E. (2005). Vitamin C in breast milk may reduce the risk of atopy in the infant. European Journal of Clinical Nutrition, 59(1), 123-128.
219. Inagaki, H., Suzuki, K., Nomoto, K., & Yoshikai, Y. (1996). Increased susceptibility to primary infection with Listeria monocytogenes in germfree mice may be due to lack of accumulation of L-selectin(+) CD44(+) T cells in sites of inflammation. Infection and Immunity, 64(8), 3280-3287.
220. Kim, Park, J., Yoon, H.-G., You, Y., Seo, Y. S., Kim, J. H., et al. (2016). Biological Activities of Fructooligosaccharides Produced by Aspergillus aculeatus in Mice Fed a High-fat Diet and Caco-2 Cell. Journal of Food and Nutrition Research, 4(6), 361-368.
221. Koletzko, B., Rodriguez-Palmero, M., Demmelmair, H., Fidler, N., Jensen, R., & Sauerwald, T. (2001). Physiological aspects of human milk lipids. Early Human Development, 65 Suppl, S3-S18.
222. Ley, R. E., Backhed, F., Turnbaugh, P., Lozupone, C. A., Knight, R. D., & Gordon, J. I. (2005). Obesity alters gut microbial ecology. Proceedings of the National Academy of Sciences of the United States of America, 102(31), 11070-11075.
223. McRorie, J., Pepple, S., & Rudolph, C. (1998). Effects of fiber laxatives and calcium docusate on regional water content and viscosity of digesta in the large intestine of the pig. Digestive Diseases and Sciences, 43(4), 738-745.
224. Odhiambo, J. A., Williams, H. C., Clayton, T. O., Robertson, C. F., Asher, M. I., & Group, I. P. T. S. (2009). Global variations in prevalence of eczema symptoms in children from ISAAC Phase Three. Journal of Allergy and Clinical Immunology, 124(6), 1251-1258 e1223.
225. Roediger, W. E., Moore, J., & Babidge, W. (1997). Colonic sulfide in pathogenesis and treatment of ulcerative colitis. Digestive Diseases and Sciences, 42(8), 1571-1579.
226. Roncarolo, M. G., Bacchetta, R., Bordignon, C., Narula, S., & Levings, M. K. (2001). Type 1 T regulatory cells. Immunological Reviews, 182, 68-79.
227. Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M., & Toda, M. (2011). Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25) breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. Journal of Immunology, 186(7), 3808-3821.
228. Shearer, G. C., Savinova, O. V., & Harris, W. S. (2012). Fish oil - How does it reduce plasma triglycerides? Biochimica Et Biophysica Acta-Molecular and Cell Biology of Lipids, 1821(5), 843-851.
229. Solvoll, K., Soyland, E., Sandstad, B., & Drevon, C. A. (2000). Dietary habits among patients with atopic dermatitis. European Journal of Clinical Nutrition, 54(2), 93-97.
230. Spiegel, J. E., Rose, R., Karabell, P., Frankos, V. H., & Schmitt, D. F. (1994). Safety and Benefits of Fructooligosaccharides as Food Ingredients. Food Technology, 48(1), 85-89.
231. Strauch, U. G., Grunwald, N., Obermeier, F., Gurster, S., & Rath, H. C. (2010). Loss of CD103+ intestinal dendritic cells during colonic inflammation. The World Journal of Gastroenterology, 16(1), 21-29.
232. Turnbaugh, P. J., Hamady, M., Yatsunenko, T., Cantarel, B. L., Duncan, A., Ley, R. E., et al. (2009). A core gut microbiome in obese and lean twins. Nature, 457(7228), 480-484.
233. Williams, H. C. (1995). Atopic eczema. British Medical Journal, 311(7015), 1241-1242.
234. Williams, H. C. (2000). Atopic dermatitis: the epidemiology, causes and prevention of atopic eczema: Cambridge University Press.