Adult lactose digestion status and effects on disease

Canadian Journal of Gastroenterology and Hepatology

Volumn 29, Issue 3, 2015, Pages 149-156

  Szilagyi, Andrew ^a  

^a MCGILL UNIVERSITY   (Canada)

Author keywords

Adaptation; Evolution; Intolerance; Lactose

Indexed keywords

LACTASE; LACTOSE;

ADULT; BIBLIOGRAPHIC DATABASE; DIGESTIVE SYSTEM FUNCTION DISORDER; ENVIRONMENTAL CHANGE; FOOD INTAKE; HUMAN; INTESTINE FLORA; LACTOSE INTOLERANCE; MEDICAL PARAMETERS; NUTRITIONAL INTOLERANCE; PHENOTYPE; POPULATION; PRIORITY JOURNAL; REVIEW; ULCERATIVE COLITIS; COLON; ENZYMOLOGY; EVIDENCE BASED MEDICINE; GENETICS; GROWTH, DEVELOPMENT AND AGING; INFLAMMATORY BOWEL DISEASES; LACTOBACILLUS; METABOLISM; MICROBIOLOGY; RISK FACTOR;

ADULT; COLON; EVIDENCE-BASED MEDICINE; HUMANS; INFLAMMATORY BOWEL DISEASES; LACTASE; LACTOBACILLUS; LACTOSE; LACTOSE INTOLERANCE; PHENOTYPE; RISK FACTORS;

EID: 84927135588     PISSN: 22912789     EISSN: 22912797     Source Type: Journal    
DOI: 10.1155/2015/904686     Document Type: Review

References (131)

1. Saviahti A, Launiala K, Kuitunen P. Congenital lactase deficiency. A clinical study on 16 patients. Arch Dis Child 1983;58:246-52.
2. Uchida N, Sakamoto O, Irie M, et al. Two novel mutations in the lactase gene in a Japanese infant with congenital lactase deficiency. Tohoku J Exp Med 2012;227:69-72.
3. Swallow DM. Genetics of lactase persistence and lactose intolerance. Ann Hum Genet 2003;37:197-219.
4. Maiuri L, Raia V, Potter J, et al. Mosaic pattern of lactase expression by villous enterocytes in human adult-type hypolactasia. Gastroenterology 1991;100:359-69.
5. KruseTA, Bolund L, Grzeschik KH, et al. The human lactase-phlorizin gene is located on chromosome 2. FEBS Lett 1988;240:123-6.
6. Enattah NS, Sahi T, Savilahti E, Terwilliger JD, Peltonen L, Järvelä I. Identification of a variant associated with adult-type hypolactasia. Nat Genet 2002;30:233-7.
7. Xu L, Sun H, Zhang X, et al. The G-22018 A allele matches the lactase persistence phenotype in northern Chinese populations. Scand J Gastroenterol 2010;45:168-74.
8. Ingram CJE, Elamin MF, Mulcare CA, et al. A novel polymorphism associated with lactose tolerance in Africa: Multiple causes for lactase persistence? Hum Genet 2007;120:779-88.
9. Tishkoff SA, Reed FA, Ranciaro A, et al. Convergent adaptation of human lactase persistence in Africa and Europe. Nat Genet 2007;39:31-40.
10. Imtiaz F, Savilahti E, Sarnesto A, et al.The T/G 13915 variant upstream of the lactase gene (LCT) is the founder allele of lactase persistence in an urban Saudi population. J Med Genet 2007;44:4e89.
11. Bersaglieri T, Sabeti PC, Patterson N, et al. Genetic signatures of strong recent positive selection at the lactase gene. Am J Hum Genet 2004;74:1111-20.
12. Burger J, Kirchner M, Bramanti B, Haak W, Thomas MG. Absence of the lactase-persistence-associated allele in early Neolithic Europeans. Proc Natl Acad Sci USA. 2007;104: 3736-41.
13. Forster P, Matsumura S. Did early humans go north or south. Science 2005;308:965-6.
14. Malyarchuk B, Derenko M, Denisova G, et al. Ancient links between Siberians and native Americans revealed by subtyping the Y chromosome haplogroup Q1A. J Hum Genet 2011;56:583-8.
15. Flatz G, Rotthauwe HW. Lactose nutrition and natural selection. Lancet 1973;2:76-7.
16. Simoons FJ. Primary adult lactose intolerance and the milking habit: a problem in biologic and cultural interrelations. II: A culture historical hypothesis. Am J Dig Dis 1970;15:695-710.
17. Simoons FJ. The geographic hypothesis and lactose malabsorption: A weighing of the evidence. Am J Dig Dis 1978;23:963-80.
18. Holden C, Mace R. Phylogenetic analysis of the evolution of lactose digestion in adults. Hum Biol 1997;69:605-28.
19. Gerbault P, Moret C, Currat M, Sanchez-Mazas A. Impact of selection and demography on the diffusion of lactase persistence. PLoS One, 2009;4:e6369doi:10.1371/journal.pone.0006369.
20. Misselwitz B, Pohl D, Fruhauf H, Fried M, Vavricka S, Fox M. Lactose malabsorpyion and intolerance: Pathogenesis, diagnosis and treatment. United Eur Gastroenterol J 2013;1:151-9.
21. Newcomer AD, McGill DB, Thomas PJ, Hofmann AF. Prospective comparison of indirect methods for detecting lactase deficiency. N Engl J Med 1975;293:1232-6.
22. Arola H. Diagnosis of hypolactasia and lactose malabsorption. Scand J Gastroeneterol 1994;202:26-35.
23. Waud JP, Matthews SB, Campbell AK. Measurement of breath hydrogen and methane, together with lactase genotype, defines the current best practice for investigation of lactose sensitivity. Ann Clin Biochem 2008;45(Pt 1):50-8.
24. Furnari M, Bonfanti D, Parodi A, et al. A comparison between lactose breath test and quick test on duodenal biopsies for diagnosing lactase deficiency in patients with self-reported lactose intolerance. J Clin Gastroenterol 2013;47:148-52.
25. Enattah NS, Kuokkanen M, Forsblom C, et al. Correlation of intestinal disaccharidase activities with the C/T-13910 variant and age. World J Gastroenterol 2007;13:3508-12.
26. Marton A, Xue X, Szilagyi A. Meta-analysis: The diagnostic accuracy of lactose breath hydrogen or lactose tolerance tests for predicting the north European lactase polymorphism C/T-13910. Aliment Pharmacol Ther 2012;35:429-40.
27. Farup PG, Monsbakken KW, Vandvik PO. Lactose malabsorption in a population with irritable bowel syndrome: Prevalence and symptoms. A case-control study. Scand J Gastroenterol 2004;7:645-9.
28. Szilagyi A, Malolepszy P, Yesovitch S, et al. Inverse dose effect of pretest dietary lactose intake on breath hydrogen results and symptoms in lactase non persistent subjects. Dig Dis Sci 2005;50:2178-82.
29. Mishkin S. Dairy sensitivity, lactose malabsorption, and elimination diets in inflammatory bowel disease. Am J Clin Nutr 1997;65:564-7.
30. Eadala P, Mathews SB, Waud JP, Gren JT, Campbell AK. Association of lactose sensitivity with inflammatory bowel disease-demonstrated by analysis of genetic polymorphism, breath gases and symptoms. Aliment Pharmacol Ther 2011;34:735-46.
31. Gibson PR, Shepherd SJ. Personal view: Food for thought-Western lifestyle and susceptibility to Crohn's disease. The FODMAP hypothesis. Aliment Pharmacol Ther 2005;21:1399-409.
32. Yang J, Fox M, Cong Y, et al. Lactose intolerance in irritable bowel syndrome patients with diarrhea: The roles of anxiety, activation of the innate mucosal system and visceral sensitivity. Aliment Pharmacol Ther 2014;39:302-11.
33. Gibson PR Shepherd SJ. Evidence-based dietary management of functional gastrointestinal symptoms: The FODMAP approach. J Gastroenterol Hepatol 2010;25:252-8.
34. Montalto M, Gallo L, Santoro L, et al. Low-dose lactose in drugs neither increases breath hydrogen excretion nor causes gastrointestinal symptoms. Aliment Pharmacol Ther 2008;28:1003-12.
35. Casellas F, Aparici A, Casaus M, Rodríguez P, Malagelada JR.Subjective perception of lactose intolerance does not always indicate lactose malabsorption. Clin Gastroenterol Hepatol 2010;8:581-6.
36. Tomba C, Baldassarri A, Coletta M, Cesana BM, Basilisco G. Is the subjective perception of lactose intolerance influenced by the psychological profile? Aliment Pharmacol Ther 2012;36:660-9.
37. Hertzler SR, Huynh BC, Savaiano DA. How much lactose is low lactose. J Am Diet Assoc 1996;96:243-6.
38. Suarez FL, Savaiano DA, Levitt MD. A comparison after the consumption of milk or lactose-hydrolyzed milk by people with self-reported severe lactose intolerance. N Engl J Med 1995;333:1-4.
39. Suarez FL, Savaiano D, Arbisi P, Levitt MD. Tolerance to the daily ingestion of two cups of milk by individuals claiming lactose intolerance. Am J Clin Nutr 1997;65:1502-6.
40. Suchy FJ, Brannon PM, Carpenter TO, et al. National institute of health consensus development conference: Lactose intolerance in health. Ann Intern Med 2010;152:792-6.
41. Hertzler SR, Savaiano DA. Colonic adaptation to daily lactose feeding in lactose maldigesters reduces lactose intolerance. Am J Clin Nutr 1996;64:232-6.
42. Savaiano DA, Ritter A, Klaenhammer TR, et al. Improving lactose digestion and symptoms of lactose intolerance with a novel galactooligosaccharide (RP-G28): A randomized, double-blind clinical trial. Nutr J 2013;12:160-9.
43. Shrier I, Szilagyi A, Correa JA. Impact of lactose containing foods and the genetics of lactase on diseases: An analytical review of population data. Nutr Cancer 2008;60:292-300.
44. Jiang, T; Savaiano, DA. In vitro lactose fermentation by human colonic bacteria is modified by Lactobacillus acidophilus supplementation. J Nutr 1997;1237:1489-95.
45. Jiang T, Savaiano DA. Modification of colonic fermentation by bifidobacteria and pH in vitro. Impact on lactose metabolism, short-chain fatty acid, and lactate production. Dig Dis Sci 1997;42:2370-7.
46. Makivuokko HA, Saarinen MT, Ouwehand AC, Rautonen NE. Effects of lactose on colon microbial community structure and function in a four-stage semi-continuous culture system. Biosci Biotechno Biochem 2006;70:2056-63.
47. Ito M, Kimura M. Influence of lactose on faecal microflora in lactose maldigesters. Microb Ecol Health Dis 1993;6:73-6.
48. Szilagyi A. Review article: Lactose-a potential prebiotic. Aliment Pharmacol Ther 2002;16:1591-602.
49. Szilagyi A, Shrier I, Heilpern D, et al. Differential impact of lactose/lactase phenotype on colonic microflora. Can J Gastroenterol 2010;24:373-9.
50. Oku T, Nakamura S, Ichinose M. Maximum permissive dose of lactose and lactitol for transitory diarrhea, and utilizable capacity for lactose in Japanese female adults. J Nutr Sci Vitaminol 2005;51:51-7.
51. Gilat T, Russo S, Gelman-Malachi E, Aldor TA. Lactase in man: A nonadaptable enzyme. Gastroenterology 1972;62:1125-7.
52. He T, Venema K, Priebe MG, Welling GW, Brummer R.-J, Vonk RJ. The role of colonic metabolism in lactose intolerance. Eur J Clinical Invest 2008;38:541-7.
53. Duncan SH, Louis P, Flint HJ. Lactate-utilizing bacteria, isolated from human feces, that produce butyrate as a major fermentation product. Appl Environ Microbiol 2004;70:5810-7.
54. Commane D, Hughes R, Short C, Rowland I. The potential mechanisms involved in the anti-carcinogenic action of probiotics. Mut Res 2005;591:276-89.
55. Severin S, Wenshui X. Milk biologically active components as nutraceuticals. Rev Crit Rev Food Sci Nutr 2005;45:645-56.
56. Szilagyi A, Nathwani U, Vinokuroff C, Correa JA, Shier I. Evaluation of relationships among national colorectal cancer mortality rates, genetic lactase non persistence status and per capita yearly milk and milk product consumption. Nut Cancer 2006;55:151-6.
57. Park Y, Leitzmann MF, Subar, et al. Dairy food, calcium, and risk of cancer in the NIH-AARP diet and health study. Arch Intern Med 2009;169:391-401.
58. Norat T, Riboli E. Dairy products and colorectal cancer: A review of possible mechanisms and epidemiological evidence. Eur J Clin Nutr 2003;57:1-17.
59. Grau MV, Baron JA, Sandler RS, et al. Prolonged effect of calcium supplementation on risk of colorectal adenomas in a randomized trial. J Natl Cancer Inst 2007;99:129-36.
60. Grau MV, Baron JA, Sandler RS, et al. Vitamin D, calcium supplementation, and colorectal adenomas: Results of a randomized trial. J Natl Cancer Inst 2003;95:1765-71.
61. Torfadottir JE, Steingrimsdottir L, Mucci L, et al. Milk intake in early life and risk of advanced prostate cancer. Am J Epidemiol 2012;175:144-53.
62. Pettersson A, Kasperzyk JL, Kenfield SA, et al. Milk and dairy consumption among men with prostate cancer and risk of metastases and prostate cancer death. Cancer Epidemiol Biomarkers Prev 2012;21:428-36.
63. Song Y, Chavarro JE, Cao Y, et al. Whole milk intake is associated with prostate cancer-specific mortality among U.S. male physicians. J Nutr 2013;143:189-96.
64. Travis RC, Appleby PN, Siddiq A, et al. Genetic variation in lactase gene, dairy product intake and risk for prostate cancer in the European prospective investigation into cancer and nutrition. Int J Cancer 2013;132:1901-10.
65. Agarwal MM, Rana SV, Mandal AK, et al. Lactose intolerance in prostate cancer patients: Incidence and associated factors. Scand J Gastroeneterol 2008;43:270-6.
66. Davies TW, Palmer, CR, Lipscombe JM. Adolescent milk, dairy product and fruit consumption and testicular cancer. Br J Cancer 1998;74:657-60.
67. Stang A, Ahrens W, Baumgrdt-Elms C. Adolescent milk fat and galactose consumption and testicular cell cancer. Cancer Epidemiol Biomark Prev 2006;15:2189-95.
68. Mao QQ, Dai Y, Lin YW, Qin J, Xie LP, Zheng XY. Milk consumption and bladder cancer risk: Meta-analysis of published epidemiological studies. Nut Cancer 2011;63:1263-71.
69. Hayatsu H, Hayatsu T. Suppressing effect of Lactobacillus casei administration on the urinary mutagenicity arising from ingestion of fried ground beef in the human. Cancer Lett 1993;73:173-9.
70. Aso Y, Akaza H, Kotake T, Tsukamoto T, Imai K, Naito S. Preventive effect of a Lactobacillus casei preparation on the recurrence of superficial bladder cancer in a double-blind trial. The BLP study group. Eur Urol 1995;27:104-9.
71. Cramer DW. Lactase persistence and milk consumption as determinants of ovarian cancer risk. Am J Epidemiol 1989;130:904-10.
72. Qin LQ, Xu JY, Wang PY, et al. Milk/dairy products consumption, galactose metabolism and ovarian cancer: Meta-analysis of epidemiological studies. Eur J Cancer Prev 2005;14:13-9.
73. Larsson SC, Orsini N, Wolk A. Milk, milk products and lactose intake and ovarian cancer risk: A meta-analysis of epidemiological studies. Int J Cancer 2006;118:431-41.
74. Genkinger JM, Hunter, DJ, Spiegelman D, et al. Dairy products and ovarian cancer: A pooled analysis of 12 cohort studies. Cancer Epidemiol Biomarkers Prev 2006;15:364-72.
75. Faber MT, Jensen A, Søgaard M, et al. Use of dairy products, lactose, and calcium and risk of ovarian cancer-results from a Danish case-control study. Acta Oncol 2012;51:454-64.
76. Mommers M, Schouten LJ, Goldbohm RA, van den Brandt PA. Dairy consumption and ovarian cancer risk in the Netherlands Cohort Study on Diet and Cancer. Br J Cancer 2006;94:165-70.
77. Schulz M, Nöthlings U, Allen N, et al. No association of consumption of animal foods with risk of ovarian cancer. Cancer Epidemiol Biomark Prev 2007;16:852-5.
78. Ganmaa D, Sato A. The possible role of female sex hormones in milk from pregnant cows in the development of breast, ovarian and corpus uteri cancers. Med Hypotheses 2005;65:1028-37.
79. Krog V, Berrino F, Sieri S, et al. Meat, eggs, dairy products, and risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Am J Clin Nutr 2009;90:602-12.
80. Dong JY, Zhang L, He K, Qin LQ. Dairy consumption and risk of breast cancer: A meta-analysis of prospective cohort studies. Breast Cancer Res Treat 2011;127:23-31.
81. Sankaranarayanan R, Varghese C, Duffy SW, Padmakumary G, Day NE, Nair MK. A case-control study of diet and lung cancer in Kerala, south India. Int J Cancer 1994;58:644-9.
82. Richman E, Rhodes JM. Review article: Evidence-based dietary advice for patients with inflammatory bowel disease. Aliment Pharmacol Ther 2013;38:1156-71.
83. Vernia P, Loizos P, Di Giuseppantonio I, Amore B, Chiappini A, Cannizzaro S. Dietary calcium intake in patients with inflammatory bowel disease. J Crohn's Colitis 2014;8:312-7.
84. Ghishan FK, Kiela PR. Advances in the understanding of mineral and bone metabolism in inflammatory bowel diseases. Am J Physiol Gastrointest Liver Physiol 2011;300:G191-201.
85. Ananthakrishnan AN, Cheng SC, Cai T, et al. Association between reduced plasma 25-hydroxy vitamin D and increased risk of cancer in patients with inflammatoy bowel diseases. Clin Gastoenterol Hepatol 2014;12:821-7.
86. Asakura H, Suzuki K, Kitahora T, Morizane T. Is there a link between food and intestinal microbes and the occurrence of Crohn's disease an ulcerative colitis. J Gastroenterol Hepatol 2008;23:1794-801.
87. Joachim G. The relationship between habits of food consumption and reported reactions to food in people with inflammatory bowel disease-testing the limits. Nutr Health 1999;13:69-83.
88. Gilat T, Hacohen D, Lilos P Langman MJ. Childhood factors in ulcerative colitis and Crohn's disease. An international cooperative study. Scand J Gastroenterol 1987;22:1009-24.
89. Jantchou P, Morois S, Clavel-Chapelon F, Boutron-Ruault MC, Carbonnel F. Animal protein intake and risk of inflammatory bowel disease: The E3N prospective study. Am J Gastroenterol 2010;105:2195-201.
90. Abubakar I, Myhill DJ, Hart AR, et al. A case-control study of drinking water and dairy products in Crohn's disease-further investigation of the possible role of Mycobacterium avium paratuberculosis. Am J Epidemiol 2007;165:776-83.
91. Buning C, Ockenaga J, Kruger S, et al. The C/C (-13910) and G/G (-22018) genotypes for adult-type hypolactasia are not associated with inflammatory bowel disease. Scand J Gastroenterol 2003;38:538-42.
92. Nolan DJ, Han DY, Lam WJ, Morgan AR, Fraser AG, Tapsell LC. Genetic adult lactase persistence is associated with risk of Crohn's disease in a New Zealand population. BMC Res Notes 2010;3:339-43.
93. Kettunen J, Silander K, Saarela O, et al. European lactase persistence genotype shows evidence of association with increase in body mass index. Hum Mol Genet 2010;19:1129-36.
94. Chen M, Pan A, Malik VS, Hu FB. Effects of dairy intake on body weight and fat: meta-analysis of randomized controlled trials. Am J Clin Nutr 2012;96:735-47.
95. Louie JC, Flood VM, Rangan AM, et al. Higher regular fat dairy consumption is associated with lower incidence of metabolic syndrome but not type 2 diabetes. Nutr Metab Cardiovasc Dis 2013;23:816-21.
96. Birlouez-Aragon I, Ravelontseheno L, Villate-Cathelineau B, Cathelineau G, Abitbol G. Disturbed galactose metabolism in elderly and diabetic humans is associated with cataract formation. J Nutr 1993;123:1370-6.
97. Nicklas TA, Haiyan Q, Hughes SO, et al. Self-percieved lactose intolerance results in lower intakes of calcium and dairy foods and is associated with hypertension and diabetes in adults. Am J Clin Nutr 2011;94:191-8.
98. Nettleton JA, Steffen LM, Loehr LR, Rosamond WD, Folsom AR. Incident heart failure is associated with lower whole-grain intake and greater high-fat dairy and egg intake in the Atherosclerosis Risk in Communities (ARIC) study. J Am Diet Assoc 2008;108:1881-7.
99. Huth PJ, Park KM. Influence of dairy product and milk fat consumption on cardiovascular disease risk: A review of the evidence. Adv Nutr 2012;3:266-85.
100. Louie JC, Flood VM, Burlitsky G, Rangan AM, Gill TP, Mitchell P. Dairy consumption and the risk of 15-year cardiovascular disease mortality in a cohort of older Australians. Nutrients 2013;5:441-54.
101. Garland CF, Garland FC. Do sunlight and vitamin D reduce the likelihood of colon cancer? Int J Epidemiol 1980;9:227-31.
102. Grant WB. A meta-analysis of second cancers after a diagnosis of non-melanoma skin cancer: Additional evidence that solar ultraviolet-B irradiance reduces the risk of internal cancers. J Steroid Biochem Mol Biol 2007;103:668-74.
103. Mohr SB, Garland CF, Gorham ED, Grant WB, Garland FC. Ultraviolet B and incidence rates of leukemia worldwide. Am J Prev Med 2011:41:68-74.
104. Simpson S Jr, Blizzard L, Otahal P, Van der Mei I, Taylor B. Latitude is significantly associated with the prevalence of multiple sclerosis: A meta-analysis. J Neurol Neurosurg Psychiatry 2011;82:1132-41.
105. Zitterman A. Vitamin D in preventive medicine: Are we ignoring the evidence? Br J Nutr 2003;89:552-72.
106. Cantorna MT, Mahon BD. Mounting evidence for vitamin D as an environmental factor affecting autoimmune disease prevalence. Exp Biol Med (Maywood) 2004;229:1136-42.
107. International Agency for Research Group. Dietary fiber, transit-time, faecal bacteria, steroids, and colon cancer in two Scandinavian populations. Lancet 1977;2:207-11.
108. Nanji AA, Denardi FG. Primary adult lactose intolerance protects against development of inflammatory bowel disease. Med Hypotheses 1986;19:1-6.
109. Itan Y, Powell A, Beaumont MA, Burger J, Thomas MG. The origins of lactase persistence in Europe. PLoS Comput Biol 2009;5:e1000491. doi:10.1371/journal.pcbi.1000491.
110. Babu J, Kumar S, Babu P, et al. Frequency of lactose malabsorption among healthy southern and northern Indian populations by genetic analysis and lactose hydrogen breath and tolerance tests. Am J Clin Nutr 2010;91:140-6.
111. Heyer E, Brazier L, Segurel L, et al. Lactase persistence in central Asia: Phenotype, genotype, and evolution. Hum Biol 2011;83:379-92.
112. Gallego Romero I, Basu Mallick C, Liebert A, et al. Herders of Indian and European cattle share their predominant allele for lactase persistence. Mol Biol Evol 2012;29:249-60.
113. Peyrin-Biroulet I, Oussalah A, Bigard M-A. Crohn's disease: The hot hypothesis. Med Hypotheses 2009;73:94-6.
114. Garg M, Lubel JS, Sparrow MP, Holt SG, Gibson PR. Review article: Vitamin D and inflammatory bowel disease-established concepts and future directions. Aliment Pharmacol Ther 2012;36:324-44.
115. Ng Sc, Bernstein CN, Vatn MH, et al. Geographical variability and environmental risk factors in inflammatory bowel disease. Gut 2013;62:630-49.
116. Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med 2009;361:2066-78.
117. Ananthakrishnan AN, Hailiang H, Nguyen DD, Sauk J, Yajnik V, Xavier RJ. Differential effect of genetic burden on disease phenotypes in Crohn's disease and ulcerative colitis: Analysis of a North American cohort. Am J Gastroenterol 2014;109:395-400.
118. Lees CW, Barrett JC, Parkes M, Satsangi J. New IBD genetics: Common pathways with other diseases. Gut 2011;60:1739-53.
119. Itan Y, Jones BL, Ingram CJE, Swallow DM, Thomas MG. A worldwide correlation of lactase persistence phenotype and genotypes. BMC Evolutionary Biol 2010;10:36 〈www.biomedcentral. com/1471-2148/10/36〉 (Accessed March 6, 2015).
120. Molodecky NA, Soon IS, Rabi D, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on a systematic review. Gastroenterology 2012;142:46-54.
121. Szilagyi A, Leighton H, Burstein B, Xue X. Latitude, sunshine, and human lactase phenotype distributions may contribute to geographic patterns of modern disease: The inflammatory bowel disease model. Clin Epidemiol2014;6:183-98.
122. Gasche C, Nemeth M, Grundtner P, Willheim-Polli C, Ferenci P, Schwarzenbacher R. Evolution of Crohn's disease-associated Nod2 mutations. Immunogenetics 2008;60:115-20.
123. Naser SA, Arce M, Khaja, et al. Role of ATG16L, NOD2 and IL23R in Crohn's disease pathogenesis. World J Gastroenterol 2012;18:412-24.
124. Alfonso-Sanchez MA, Perez-Miranda AM, Garcia-Obregon S, Pena JA. An evolutionary approach to the high frequency of the delta F508 CFTR mutation in European populations. Med Hypotheses 2010;74:989-92.
125. Modiano G, Ciminellui BM, Pignatti PF. Cystic fibrosis and lactase persistence: A possible correlation. Eur J Hum Genet 2007;15:255-9.
126. Madry E, Fidler E, Sobczynska-Tomaszewska A, et al. Mild CFTR mutations and genetic predisposition to lactase persistence in cystic fibrosis. Eur J Hum Genet 2011;19:748-52.
127. Truedsson M, Carlson J, Simren M, Ohlsson B. Polymorphism in the oxytocin promoter region in patients with lactase non-persistence is not related to symptoms. BMC Gastroenterol 2009;9:90-107.
128. Sacerdote C, Guarrera S, Smith GD, et al. Lactase persistence and bitter taste response: Instrumental variables and Mendelian randomization in epidemiologic studies of dietary factors and cancer risk. Am J Epidemiol 2007;166:576-81.
129. Wu GD, Chen J, Hoffmann C, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science 2011;334:105-8.
130. Arumugam M, Raes J, Pelletier E, et al. Enterotypes of the human gut microbiome. Nature 2011;473:174-80.
131. Hecht G. AGA's approach to the microbiome. 2014;146:1119-21.