In our colonoscopy-based study, diverticulosis showed a significant association with BN chewing in Taiwanese male. No obvious association in the female group was the fact of few participants had the habit of BN chewing which is compatible with low prevalence rates of BN chewing behavior among women in Taiwan.12 Furthermore, BN chewing had prominent effect in logistic regression among the combination analysis among most seen substances: cigarette, alcohol and BN. Lin et al. had showed that BN consumption had significant dose-response effects on general obesity. 13 To better understanding how much the obesity played in the association between BN chewing and diverticulosis, our subgroup analysis found obesity weighting the BN chewing in the presence of diverticulosis. As far as we are concerned, we first examined the relationship between diverticulosis and BN chewing.
Diverticulosis is a condition with the presence of colonic diverticula, and previous study showed about 4% of patient will develop acute diverticulitis in 11-years follow-up. 14 Although the clear pathological mechanisms that cause the formation of colonic diverticula are still unknown, modern studies used to believe that there were complex interactions including lifestyle, colonic dysbiosis, colonic motility, genetic factors, and microscopic inflammation.15 However, the chain between inflammation(systemic or mucosal) and the formation of asymptomatic diverticulosis was broken since Peery et al. claimed that colonic diverticulosis was not associated with mucosal inflammation. 16
BN chewing, also known as betel quid or areca nut chewing, was thought to possess digestion improvement and refreshing by the users.2 However, its health benefits is lack of evidence and on the other hand, reviewing evidence of BN toxicity, the IARC has deemed BN (with or without tobacco) as group 1 carcinogen to humans since 2004.4 Furthermore, BN is not only an addictive substance but also causes systemic effects which are mainly due to the principle alkaloid arecoline with the activation of muscarinic receptors and acetylcholine receptors.17
There are some mechanisms linking diverticulosis and BN chewing. First, BN chewing is associated to increasing gastrointestinal motility which is noted among patients with diverticulosis.18 The possible mechanism for arecoline causing increasing gastrointestinal motility may be the result of stimulation of M3 receptor at distal colonic smooth muscle.19 Furthermore, substances in BN stimulate the release of inflammatory mediators: prostanoids, interleukin6, and tumor necrosis factor-α20, and reactive oxygen species. They also activate nuclear factor-κβ21, which are changes with the potential to cause chronic inflammation. The studies mentioned above could support our finding that BN chewing had higher prevalence of diverticulosis. In recent population-based study, Jarbrink-Sehgal et al. found no low-grade colonic inflammation in subjects with diverticulosis by pathologic evidence which highlighted the other possible mechanisms for the formation of diverticulosis.22 Jones RB et al. also indicated no obvious alternation of gut microbiota with or without diverticulosis.23 Through recent studies, the important association between colonic motility and diverticulosis goes without saying.
The present study has some notable limitations. First, it has a cross-sectional design; therefore, the causal relationship between BN chewing and diverticulosis was not assessed. A long-term observation period should be considered in future studies. Second, the presence of diverticulum was observed by colonic scope, and was recorded only with the presence without further subgroup analysis for the right, left, or sigmoid diverticulosis. Third, the questionnaire of daily quantity of betel use was not performed for further dosage effect evaluation. In addition, the participants in our study could not represent nationally, so further study for general population was necessary to obtain external validation.