Suppression of gastric acid secretion in patients with gastroesophageal reflux disease results in gastric bacterial overgrowth and deconjugation of bile acids

Theisen, Jörg; Nehra, D; Citron, Diane M.; Johansson, Jan; Hagen, Jeffrey A.; Crookes, Peter F.; DeMeester, Steven R.; Bremner, Cedric G.; DeMeester, Tom R.; Peters, Jeffrey H.

doi:10.1016/s1091-255x(00)80032-3

Cited by 203 publications

(142 citation statements)

References 17 publications

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“…While our data for abscess was not statistically significant, there appeared to be a trend towards higher rate of infection. Of the cultures that were positive, there was a higher rate of Gram-negative (enteric) This data supports the conclusion of several studies on rodents and humans that found an association between acid suppression and bacterial overgrowth/infection [6][7][8][9]. In a landmark study by Franklin et al, it was found that the previously held notion of a ''sterile'' foregut was challenged by the finding of polymicrobial gastric flora.…”

Section: Discussionsupporting

confidence: 73%

The impact of proton-pump inhibitors on intraperitoneal sepsis: a word of caution for transgastric NOTES procedures

et al. 2009

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Background During transgastric natural orifice transluminal endoscopic surgery (NOTES), there is an iatrogenic perforation of the gastric wall with leakage of gastric contents into the peritoneal cavity. The aim of this study is to determine the effect of proton-pump inhibitors (PPI) and alterations of gastric pH on infection during transgastric surgery. Methods Thirty 250-g male Sprague-Dawley rats were divided into a study group (SG, n = 15) and a control group (CG, n =15). SG were given 5 mg/kg pantoprazole for 3 days before procedure and another dose 1 h before. CG received saline at similar time points. A mini-laparotomy with gastrotomy was performed. Aspiration of 2.0 cc gastric contents was removed from the stomach and injected into the peritoneal cavity of both groups. Gastric pH and peritoneal pH levels were obtained. Gastric aspirate was sent for culture. White blood cell counts (WBC) were obtained on postoperative days 1, 7, and 14, and C-reactive protein (CRP) levels were obtained on postoperative day 1. At day 14, a necropsy was performed and aerobic and anaerobic cultures of the peritoneal cavity were obtained. Results There were no deaths in either group. The average gastric pH in the SG was 5.13 versus 3.26 (p = 0.03) in the CG. The average peritoneal pH was similar in both groups. The WBC in the SG was 4.5 vs. 3.5 (1,000 cells/ mm) in the CG. There was no elevation in CRP levels in either group. Bacterial cultures were positive in 3/15 (20%) rats in the CG and in 9/15 (60%) in the SG (p = 0.008). Intra-abdominal abscesses were found in 2/15 (13%) rats in the CG and in 5/15 (33%) in the SG (p = 0.08). Conclusions Pretreatment with a PPI resulted in a higher rate of peritoneal bacterial contamination and abscess formation. The acidic environment of the stomach appears to be protective against infection when intraperitoneal contamination occurs as a result of gastrotomy.

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Section: Discussionsupporting

confidence: 73%

The impact of proton-pump inhibitors on intraperitoneal sepsis: a word of caution for transgastric NOTES procedures

et al. 2009

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“…Famotidine was shown not to affect serum bile acid concentrations in healthy humans. 22 Although 1 study in humans showed that omeprazole significantly lowered the concentration of taurine-conjugated bile acids as a result of bacterial overgrowth, 23 only 1 cat in our study was receiving this medication. The results of our study still were significant when this 1 cat was removed from statistical analysis, with cats that had predominantly large intestinal clinical signs having significantly lower whole-blood taurine concentrations than cats with small intestinal and mixed bowel clinical signs (P = 0.040), and this finding also was significant when assessed only in cats with chronic inflammatory enteropathy (P = 0.025).…”

Section: Discussionmentioning

confidence: 69%

Whole-blood taurine concentrations in cats with intestinal disease

2018

Advances in Small Animal Medicine and Surgery

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Background: Increased delivery of taurine-conjugated bile acids to the distal bowel can lead to dysbiosis resulting in colitis in mouse models of inflammatory bowel disease. A similar situation also could occur in cats with intestinal disease and might therefore result in decreased whole-body taurine concentration.Hypothesis/Objectives: To determine whether whole-blood taurine concentrations are decreased at the time of diagnosis in cats with intestinal disease and to correlate concentrations with clinical and laboratory variables.Animals: Twenty-one cats with chronic inflammatory enteropathy and 7 cats with intestinal neoplasia from the University of Bristol.Methods: Cats that had undergone a thorough investigation consisting of a CBC, serum biochemistry, serum cobalamin and folate concentrations, transabdominal ultrasound examination and histopathology of intestinal biopsy specimens, as well as additional testing if indicated, were included. Whole-blood from these cats collected at the time of histologic diagnosis and stored in ethylenediaminetetraacetic acid was retrospectively analyzed for taurine with an automated high-performance liquid chromatography amino acid analyzer.Results: Although whole-blood taurine concentrations remained within the reference range, those cats with predominantly large intestinal clinical signs had significantly lower concentrations than did cats with small intestinal and mixed bowel clinical signs (P = 0.033) and this difference also was significant when assessed only in cats with chronic inflammatory enteropathy (P = 0.019).Conclusions and Clinical Importance: Additional studies are needed to determine whether large intestinal signs in cats with chronic inflammatory enteropathy are caused by alterations in the microbiota arising as a consequence of increased delivery of taurine-conjugated bile acids.

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“…25,28,29 Bile acids have been shown to activate both survival and anti-apoptotic pathways in cultured cells, and unconjugated bile acids are increased in the refluxate in patients on a high-fat diet and in patients taking proton pump inhibitors. 30 The exposure to bile acids has been reported to lead to promoter demethylation and activation of the Cdx2 promoter in esophageal cells. 25,31 The L2-IL-1b mouse model demonstrates that bile acids accelerate the development of BE and EAC, but only in the setting of an existing inflammatory condition in the esophagus (e.g., in L2-IL-1β mice), analogous to reflux-induced esophagitis in humans.…”

Section: Importance Of Inflammation and Bile Acidsmentioning

confidence: 99%

Barrett esophagus

et al. 2012

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T he incidence of esophageal adenocarcinoma (EAC) is rapidly rising in the western world and accounts for 2% of all cancer-related deaths. The precursor lesion for EAC is Barrett esophagus (BE), which is strongly associated with gastresophageal reflux disease. A major limitation to the study of EAC has been the absence of tractable and genetically modifiable preclinical models of BE. A mouse model of BE and EAC that resembles human disease could provide novel insights into the origins and molecular pathogenesis of BE. In addition, validated animal models could help stratify BE patients given the limited predictive power of current standard endoscopic measures and clinical assessment. Here, we review the findings from recently developed mouse models of BE and EAC and their impact on clinical decision making, surveillance programs and therapeutic options. The data, taken together, suggest potential origins of BE from the gastric cardia, a role of bile acid and hypergatrinemia for carcinogenesis, a growing importance for columnar-like epithelium and a critical role for Notch signaling.

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Suppression of gastric acid secretion in patients with gastroesophageal reflux disease results in gastric bacterial overgrowth and deconjugation of bile acids

Cited by 203 publications

References 17 publications

The impact of proton-pump inhibitors on intraperitoneal sepsis: a word of caution for transgastric NOTES procedures

The impact of proton-pump inhibitors on intraperitoneal sepsis: a word of caution for transgastric NOTES procedures

Whole-blood taurine concentrations in cats with intestinal disease

Barrett esophagus

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