Background and Aim: The etiology and pathogenesis of Barrett’s esophagus (BE) have been widely studied during recent decades. However, the association between BE and possible risk factors, including abdominal obesity (AO), metabolic syndrome (MetS), insulin resistance (IR), and the microbiome has not reached a consensus and lacks a systematic assessment. The purpose of our study is to evaluate, quantify, and summarize the association between these factors and BE risk. Methods: A systematic search of Pubmed, Embase, and Cochrane Library databases was performed to identify relevant studies before September 2018. Studies were estimated with the OR, the weighted mean difference (WMD), and the 95% CI by using a random effects model. Subgroup analysis and publication bias were also performed. Results: A total of 46 citations were included in the analysis, and 119,273 subjects were analyzed (AO 13, MetS 15, IR 9, and microbiome: 9). The pooled results showed that AO (p < 0.01, OR 1.30, 95% CI 1.11–1.52, I2 = 31.9%), MetS (p < 0.01, OR 1.68, 95% CI 1.40–2.01, I2 = 87.6%), and IR (p < 0.01, WMD 0.23, 95% CI 0.11–0.35, I2 = 55.8%) were all significantly associated with an increased risk of BE, but except for the microbiome (p > 0.05, OR 1.27, 95% CI 0.66–2.43, I2 = 46.7%). In addition, subgroup analyses were stratified by waist-to-hip ratio, waist circumference, body mass index, diagnosis criteria, strain type, geographical region, and study design, respectively. Moreover, we observed no evidence of publication bias in Egger’s and Begg’s tests. Conclusions: Our study reveals that AO, MetS, and IR are significantly associated with BE risk, except for the microbiome. The mechanism of BE induced by 3 risk factors should be further explored.

1.
Spechler SJ. Barrett esophagus and risk of esophageal cancer: a clinical review.
JAMA
. 2013 Aug;310(6):627–36.
2.
Hagen CE, Lauwers GY, Mino-Kenudson M. Barrett esophagus: diagnostic challenges.
Semin Diagn Pathol
. 2014 Mar;31(2):100–13.
3.
Tadiparthi R, Bansal A, Sharma P. What’s new in columnar lined esophagus (Barrett’s metaplasia)?
Curr Opin Gastroenterol
. 2008 Jul;24(4):516–20.
4.
Shiota S, Singh S, Anshasi A, El-Serag HB. Prevalence of Barrett’s Esophagus in Asian Countries: A Systematic Review and Meta-analysis.
Clin Gastroenterol Hepatol
. 2015 Nov;13(11):1907–18.
5.
Falk GW, Jacobson BC, Riddell RH, Rubenstein JH, El-Zimaity H, Drewes AM, et al. Barrett’s esophagus: prevalence-incidence and etiology-origins.
Ann N Y Acad Sci
. 2011 Sep;1232(1):1–17.
6.
Shaheen NJ, Falk GW, Iyer PG, Gerson LB; American College of Gastroenterology. ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus.
Am J Gastroenterol
. 2016 Jan;111(1):30–50.
7.
Thrift AP. Determination of risk for Barrett’s esophagus and esophageal adenocarcinoma.
Curr Opin Gastroenterol
. 2016 Jul;32(4):319–24.
8.
Kendall BJ, Macdonald GA, Hayward NK, Prins JB, O’Brien S, Whiteman DC; Study of Digestive Health. The risk of Barrett’s esophagus associated with abdominal obesity in males and females.
Int J Cancer
. 2013 May;132(9):2192–9.
9.
Drahos J, Ricker W, Pfeiffer RM, Cook MB. Metabolic syndrome and risk of esophageal adenocarcinoma in elderly patients in the United States: an analysis of SEER-Medicare data.
Cancer
. 2017 Feb;123(4):657–65.
10.
Chandar AK, Iyer PG. Role of Obesity in the Pathogenesis and Progression of Barrett’s Esophagus.
Gastroenterol Clin North Am
. 2015 Jun;44(2):249–64.
11.
Baghdadi J, Chaudhary N, Pei Z, Yang L. Microbiome, innate immunity, and esophageal adenocarcinoma.
Clin Lab Med
. 2014 Dec;34(4):721–32.
12.
Hunt RH, Yaghoobi M. The Esophageal and Gastric Microbiome in Health and Disease.
Gastroenterol Clin North Am
. 2017 Mar;46(1):121–41.
13.
Sanghi V, Thota PN. Barrett’s esophagus: novel strategies for screening and surveillance.
Ther Adv Chronic Dis
. 2019 Mar;10:2040622319837851.
14.
Hu L, Huang X, You C, Li J, Hong K, Li P, et al. Prevalence of overweight, obesity, abdominal obesity and obesity-related risk factors in southern China.
PLoS One
. 2017 Sep;12(9):e0183934.
15.
Du X, Hidayat K, Shi BM. Abdominal obesity and gastroesophageal cancer risk: systematic review and meta-analysis of prospective studies.
Biosci Rep
. 2017 May;37(3):37.
16.
Zafar U, Khaliq S, Ahmad HU, Manzoor S, Lone KP. Metabolic syndrome: an update on diagnostic criteria, pathogenesis, and genetic links.
Hormones (Athens)
. 2018 Sep;17(3):299–313.
17.
Oda E. Historical perspectives of the metabolic syndrome.
Clin Dermatol
. 2018 Jan-Feb;36(1):3–8.
18.
Wang G. Raison d’être of insulin resistance: the adjustable threshold hypothesis.
J R Soc Interface
. 2014 Dec;11(101):20140892.
19.
Tang Q, Li X, Song P, Xu L. Optimal cut-off values for the homeostasis model assessment of insulin resistance (HOMA-IR) and pre-diabetes screening: developments in research and prospects for the future.
Drug Discov Ther
. 2015 Dec;9(6):380–5.
20.
Clemons NJ, Phillips WA, Lord RV. Signaling pathways in the molecular pathogenesis of adenocarcinomas of the esophagus and gastroesophageal junction.
Cancer Biol Ther
. 2013 Sep;14(9):782–95.
21.
May M, Abrams JA. Emerging Insights into the Esophageal Microbiome.
Curr Treat Options Gastroenterol
. 2018 Mar;16(1):72–85.
22.
Zaidi AH, Kelly LA, Kreft RE, Barlek M, Omstead AN, Matsui D, et al. Associations of microbiota and toll-like receptor signaling pathway in esophageal adenocarcinoma.
BMC Cancer
. 2016 Feb;16(1):52.
23.
Munch NS, Fang HY, Ingermann J, Maurer HC, Anand A, Kellner V, et al. High-fat Diet Accelerates Carcinogenesis in a Mouse Model of Barrett's Esophagus via Interleukin 8 and Alterations to the Gut Microbiome.
Gastroenterology
. 2019 Aug;157(2):492–506.e2.
24.
Matsuzaki J, Suzuki H, Kobayakawa M, Inadomi JM, Takayama M, Makino K, et al. Association of Visceral Fat Area, Smoking, and Alcohol Consumption with Reflux Esophagitis and Barrett’s Esophagus in Japan.
PLoS One
. 2015 Jul;10(7):e0133865.
25.
He Q, Li JD, Huang W, Zhu WC, Yang JQ. Metabolic syndrome is associated with increased risk of Barrett esophagus: A meta-analysis.
Medicine (Baltimore)
. 2016 Aug;95(31):e4338.
26.
Holub JL, Silberg DG, Michaels LC, Williams JL, Morris CD, Eisen G. Acid-related upper endoscopy findings in patients with diabetes versus non-diabetic patients.
Dig Dis Sci
. 2010 Oct;55(10):2853–9.
27.
Blackett KL, Siddhi SS, Cleary S, Steed H, Miller MH, Macfarlane S, et al. Oesophageal bacterial biofilm changes in gastro-oesophageal reflux disease, Barrett’s and oesophageal carcinoma: association or causality?
Aliment Pharmacol Ther
. 2013 Jun;37(11):1084–92.
28.
Liu N, Ando T, Ishiguro K, Maeda O, Watanabe O, Funasaka K, et al. Characterization of bacterial biota in the distal esophagus of Japanese patients with reflux esophagitis and Barrett’s esophagus.
BMC Infect Dis
. 2013 Mar;13(1):130.
29.
El-Serag HB, Hashmi A, Garcia J, Richardson P, Alsarraj A, Fitzgerald S, et al. Visceral abdominal obesity measured by CT scan is associated with an increased risk of Barrett’s oesophagus: a case-control study.
Gut
. 2014 Feb;63(2):220–9.
30.
Sawada A, Fujiwara Y, Nagami Y, Tanaka F, Yamagami H, Tanigawa T, et al. Alteration of Esophageal Microbiome by Antibiotic Treatment Does Not Affect Incidence of Rat Esophageal Adenocarcinoma.
Dig Dis Sci
. 2016 Nov;61(11):3161–8.
31.
Drahos J, Ricker W, Pfeiffer RM, Cook MB. Metabolic syndrome and risk of esophageal adenocarcinoma in elderly patients in the United States: an analysis of SEER-Medicare data.
Cancer
. 2017 Feb;123(4):657–65.
32.
Kramer JR, Fischbach LA, Richardson P, Alsarraj A, Fitzgerald S, Shaib Y, et al. Waist-to-hip ratio, but not body mass index, is associated with an increased risk of Barrett's esophagus in white men.
Clin Gastroenterol Hepatol
. 2013;11:373–81.e371.
33.
Akiyama T, Yoneda M, Maeda S, Nakajima A, Koyama S, Inamori M. Visceral obesity and the risk of Barrett’s esophagus.
Digestion
. 2011;83(3):142–5.
34.
Nishida C, Ko GT, Kumanyika S. Body fat distribution and noncommunicable diseases in populations: overview of the 2008 WHO Expert Consultation on Waist Circumference and Waist-Hip Ratio.
Eur J Clin Nutr
. 2010 Jan;64(1):2–5.
35.
Slattery ML, Ferucci ED, Murtaugh MA, Edwards S, Ma KN, Etzel RA, et al. Associations among body mass index, waist circumference, and health indicators in American Indian and Alaska Native adults.
Am J Health Promot
. 2010 Mar-Apr;24(4):246–54.
36.
Mitchell DR, Derakhshan MH, Wirz AA, Ballantyne SA, McColl KE. Abdominal Compression by Waist Belt Aggravates Gastroesophageal Reflux, Primarily by Impairing Esophageal Clearance.
Gastroenterology
. 2017 Jun;152(8):1881–8.
37.
Lee SW, Lien HC, Lee TY, Tung CF, Yeh HZ, Chang CS. Impact of Obesity on a Chinese Population with Erosive Esophagitis and Barrett’s Esophagus.
Gut Liver
. 2017 May;11(3):377–82.
38.
Lin XH, Luo JC. Metabolic syndrome and gastrointestinal-hepatobiliary diseases.
J Chin Med Assoc
. 2017 Jan;80(1):3–4.
39.
Cadman L, Nelsen EM, Tian J, Schleck C, Zinsmeister AR, Locke GR, et al. Metabolic Syndrome is a Risk Factor for Barrett’s Esophagus: A Population Based Case Control Study.
Gastroenterology
. 2011;140(5):140.
40.
Veugelers PJ, Porter GA, Guernsey DL, Casson AG. Obesity and lifestyle risk factors for gastroesophageal reflux disease, Barrett esophagus and esophageal adenocarcinoma.
Dis Esophagus
. 2006;19(5):321–8.
41.
Lebovitz HE. Insulin resistance: definition and consequences.
Exp Clin Endocrinol Diabetes
. 2001;109(suppl 2):S135–48.
42.
Greer KB, Thompson C, Brenner L, Bednarchik B, Falk GW, Grady WM, et al. 15 Insulin Resistance and Central Adiposity as a Risk Factors for Barrett’s Esophagus.
Gastroenterology
. 2010;138(5):S-2.
43.
Thrift AP, Hilal J, El-Serag HB. Metabolic syndrome and the risk of Barrett’s oesophagus in white males.
Aliment Pharmacol Ther
. 2015 Jun;41(11):1182–9.
44.
Charmandari E, Weise M, Bornstein SR, Eisenhofer G, Keil MF, Chrousos GP, et al. Children with classic congenital adrenal hyperplasia have elevated serum leptin concentrations and insulin resistance: potential clinical implications.
J Clin Endocrinol Metab
. 2002 May;87(5):2114–20.
45.
Winzer BM, Paratz JD, Whitehead JP, Whiteman DC, Reeves MM. The feasibility of an exercise intervention in males at risk of oesophageal adenocarcinoma: a randomized controlled trial.
PLoS One
. 2015 Feb;10(2):e0117922.
46.
Wang ZK, Yang YS. Upper gastrointestinal microbiota and digestive diseases.
World J Gastroenterol
. 2013 Mar;19(10):1541–50.
47.
Baba Y, Iwatsuki M, Yoshida N, Watanabe M, Baba H. Review of the gut microbiome and esophageal cancer: pathogenesis and potential clinical implications.
Ann Gastroenterol Surg
. 2017 Jun;1(2):99–104.
48.
Ajayi TA, Cantrell S, Spann A, Garman KS. Barrett’s esophagus and esophageal cancer: links to microbes and the microbiome.
PLoS Pathog
. 2018 Dec;14(12):e1007384.
49.
Snider EJ, Compres G, Freedberg DE, Giddins MJ, Khiabanian H, Lightdale CJ, et al. Barrett’s esophagus is associated with a distinct oral microbiome.
Clin Transl Gastroenterol
. 2018 Feb;9(3):135.
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