Systematic review: the role of bile acids in the pathogenesis of gastro-oesophageal reflux disease and related neoplasia

McQuaid, Kenneth R.; Laine, Loren; Fennerty, M. Brian; Souza, Rhonda F.; Spechler, Stuart J.

doi:10.1111/j.1365-2036.2011.04709.x

Cited by 168 publications

(160 citation statements)

References 102 publications

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“…Bile fluid consisted of a mixture of conjugated bile salts (400 μmol/L) considered to be “physiologic” 29, 30 (Supplementary Methods). …”

Section: Methodsmentioning

confidence: 99%

NF‐κB inhibition reverses acidic bile‐induced miR‐21, miR‐155, miR‐192, miR‐34a, miR‐375 and miR‐451a deregulations in human hypopharyngeal cells

Doukas¹,

Vageli²,

Sasaki³

2018

J Cellular Molecular Medi

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We previously demonstrated that acidic bile activates NF‐κB, deregulating the expression of oncogenic miRNA markers, in pre‐malignant murine laryngopharyngeal mucosa. Here, we hypothesize that the in vitro exposure of human hypopharyngeal cells to acidic bile deregulates cancer‐related miRNA markers that can be reversed by BAY 11‐7082, a pharmacologic NF‐κB inhibitor. We repetitively exposed normal human hypopharyngeal primary cells and human hypopharyngeal keratinocytes to bile fluid (400 μmol/L), at pH 4.0 and 7.0, with/without BAY 11‐7082 (20 μmol/L). We centred our study on the transcriptional activation of oncogenic miR‐21, miR‐155, miR‐192, miR‐34a, miR‐375, miR‐451a and NF‐κB‐related genes, previously linked to acidic bile‐induced pre‐neoplastic events. Our novel findings in vitro are consistent with our hypothesis demonstrating that BAY 11‐7082 significantly reverses the acidic bile‐induced oncogenic miRNA phenotype, in normal hypopharyngeal cells. BAY 11‐7082 strongly inhibits the acidic bile‐induced up‐regulation of miR‐192 and down‐regulation of miR‐451a and significantly decreases the miR‐21/375 ratios, previously related to poor prognosis in hypopharyngeal cancer. This is the first in vitro report that NF‐κB inhibition reverses acidic bile‐induced miR‐21, miR‐155, miR‐192, miR‐34a, miR‐375 and miR‐451a deregulations in normal human hypopharyngeal cells, suggesting that acidic bile‐induced events are directly or indirectly dependent on NF‐κB signalling.

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“…Bile fluid consisted of a mixture of conjugated bile salts (400 μmol/L) considered to be “physiologic” 29, 30 (Supplementary Methods). …”

Section: Methodsmentioning

confidence: 99%

NF‐κB inhibition reverses acidic bile‐induced miR‐21, miR‐155, miR‐192, miR‐34a, miR‐375 and miR‐451a deregulations in human hypopharyngeal cells

Doukas¹,

Vageli²,

Sasaki³

2018

J Cellular Molecular Medi

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“…Potentially important components of this refluxate are bile acids, including cholic Obesity and gastric cardia cancer 29 acid, chenodeoxycholic acid, and the secondarily dehydroxylated deoxycholic acid [68]. Bile acids may be especially relevant in the origin of gastroesophageal junction cancers, since they have recently been shown to also induce signaling pathways with metabolic consequences [69,70].…”

Section: Possible Mechanisms Linking Obesity With Gcamentioning

confidence: 99%

Obesity and related risk factors in gastric cardia adenocarcinoma

Olefson

Moss

2014

Gastric Cancer

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Over recent decades, the incidence of cancers of the gastroesophageal junction, including gastric cardia tumors, has increased markedly. This is a trend that has been well documented, especially in studies from the USA and northern Europe that have also demonstrated a concomitant rise in the ratio of cardia to distal gastric cancers. The rise in the prevalence of gastric cardia adenocarcinoma has been paralleled by the worldwide obesity epidemic, with almost all epidemiological studies reporting increased body mass index and obesity increase the risk of cardia cancer development. However, the strength of this association is less marked than the link between obesity and esophageal adenocarcinoma, and the mechanisms remain poorly understood. Other possible confounders of the relationship between obesity and cardia cancer include the decline in Helicobacter pylori infection and the widespread use of proton pump inhibitors, although these have rarely been controlled for in case-control and cohort studies investigating associations between obesity and cardia cancer. We review these epidemiological trends and discuss proposed mechanisms for the association, drawing attention to controversies over the difficulty of defining cardia cancer. The relative paucity of high-quality epidemiological studies from other regions of the world should prompt further investigation of this issue, especially in populations undergoing rapid socioeconomic change.

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“…However, there are no data yet to support such speculation. Th e potential relevance of the presence of bile for GERD is summarized in a recent systematic review suggesting that bile acids contribute to the pathogenesis of GERD symptoms, esophagitis, and Barrett ' s metaplasia ( 34 ).…”

Section: The Acid Pocket In Health and Diseasementioning

confidence: 99%

The Acid Pocket: A Target for Treatment in Reflux Disease?

Kahrilas

McColl

Fox³

et al. 2013

American Journal of Gastroenterology

133

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The nadir esophageal pH of refl ux observed during pH monitoring in the postprandial period is often more acidic than the concomitant intragastric pH. This paradox prompted the discovery of the " acid pocket " , an area of unbuffered gastric acid that accumulates in the proximal stomach after meals and serves as the reservoir for acid refl ux in healthy individuals and gastroesophageal refl ux disease (GERD) patients. However, there are differentiating features between these populations in the size and position of the acid pocket, with GERD patients predisposed to upward migration of the proximal margin onto the esophageal mucosa, particularly when supine. This upward migration of acid, sometimes referred to as an " acid fi lm " , likely contributes to mucosal pathology in the region of the squamocolumnar junction. Furthermore, movement of the acid pocket itself to a supradiaphragmatic location with hiatus hernia increases the propensity for acid refl ux by all conventional mechanisms. Consequently, the acid pocket is an attractive target for GERD therapy. It may be targeted in a global way with proton pump inhibitors that attenuate acid pocket development, or with alginate / antacid combinations that colocalize with the acid pocket and displace it distally, thereby demonstrating the potential for selective targeting of the acid pocket in GERD.

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Systematic review: the role of bile acids in the pathogenesis of gastro-oesophageal reflux disease and related neoplasia

Abstract: SUMMARY BackgroundFactors other than acid may play a role in gastro-oesophageal reflux disease (GERD) and its complications.

Cited by 168 publications

References 102 publications

NF‐κB inhibition reverses acidic bile‐induced miR‐21, miR‐155, miR‐192, miR‐34a, miR‐375 and miR‐451a deregulations in human hypopharyngeal cells

NF‐κB inhibition reverses acidic bile‐induced miR‐21, miR‐155, miR‐192, miR‐34a, miR‐375 and miR‐451a deregulations in human hypopharyngeal cells

Obesity and related risk factors in gastric cardia adenocarcinoma

The Acid Pocket: A Target for Treatment in Reflux Disease?

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