Gastric Acid Suppression Is Associated with an Increased Risk of Adverse Outcomes in Inflammatory Bowel Disease

Shah, Rajesh; Richardson, Peter; Yu, Hong Jing; Kramer, Jennifer R.; Hou, Jason K.

doi:10.1159/000455008

Cited by 46 publications

(35 citation statements)

References 15 publications

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“…Regarding IBDs, various observations have led researchers to postulate that chronic PPI administration may have a negative effect on such conditions[129,130]. At present, the data on microbial imbalance during IBD have not been not fully elucidated.…”

Section: Colonmentioning

confidence: 99%

Proton pump inhibitors and dysbiosis: Current knowledge and aspects to be clarified

Bruno¹,

Zaccari²,

Rocco³

et al. 2019

WJG

181

158

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Proton pump inhibitors (PPIs) are common medications within the practice of gastroenterology. These drugs, which act through the irreversible inhibition of the hydrogen/potassium pump (H+/K+-ATPase pump) in the gastric parietal cells, are used in the treatment of several acid-related disorders. PPIs are generally well tolerated but, through the long-term reduction of gastric acid secretion, can increase the risk of an imbalance in gut microbiota composition ( i.e ., dysbiosis). The gut microbiota is a complex ecosystem in which microbes coexist and interact with the human host. Indeed, the resident gut bacteria are needed for multiple vital functions, such as nutrient and drug metabolism, the production of energy, defense against pathogens, the modulation of the immune system and support of the integrity of the gut mucosal barrier. The bacteria are collected in communities that vary in density and composition within each segment of the gastrointestinal (GI) tract. Therefore, every change in the gut ecosystem has been connected to an increased susceptibility or exacerbation of various GI disorders. The aim of this review is to summarize the recently available data on PPI-related microbiota alterations in each segment of the GI tract and to analyze the possible involvement of PPIs in the pathogenesis of several specific GI diseases.

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Section: Colonmentioning

confidence: 99%

Proton pump inhibitors and dysbiosis: Current knowledge and aspects to be clarified

Bruno¹,

Zaccari²,

Rocco³

et al. 2019

WJG

181

158

View full text Add to dashboard Cite

show abstract

“…In addition, they also found significant associations between PPIs and mild flares, which suggested that overall acid suppression with implied changes in the intestinal microbiota may be a driving factor. To confirm these associations between PPI use and the outcome of IBD, Shah et al [36] conducted a nested case-control study of patients with IBD within a large, national patient care database. They showed that prescriptions for PPIs were associated with an increased risk of IBD-related hospitalization or surgery in ulcerative colitis patients (adjusted incidence density ratio 1.11, 95% CI 1.02-1.21) and CD patients (adjusted incidence density ratio 1.12, 95% CI 1.02-1.22).…”

Section: Infectious and Inflammatory Diseases Possibly Associated Witmentioning

confidence: 99%

Intestinal Dysbiosis Secondary to Proton-Pump Inhibitor Use

Naito

Kashiwagi²,

Takagi³

et al. 2018

Digestion

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Background: Gut dysbiosis associated with the use of proton-pump inhibitors (PPIs) has been found to lead to the occurrence of infectious and inflammatory adverse events. A longitudinal observational cohort study has demonstrated the heightened risk of death associated with PPI use. Summary: We evaluated meta-analyses to determine the association between PPI use and infectious and inflammatory diseases. Meta-analyses showed that PPI use is a potential risk for the development of enteric infections caused by Clostridium difficile, as well as small intestinal bacterial overgrowth, spontaneous bacterial peritonitis, community-acquired pneumonia, hepatic encephalopathy, and adverse outcomes in inflammatory bowel disease. We also examined changes in the composition and function of the gut microbiota with the use of PPIs. PPI use significantly increased the presence of Streptococcaceae and Enterococcaceae, which are risk factors for C. difficile infection, and decreased that of Faecalibacterium, a commensal anti-inflammatory microorganism. Key Message: High-throughput, microbial 16S rRNA gene sequencing has allowed us to investigate the association between the gut microbiome and PPI use. Future prospective comparison studies are necessary to confirm this association, and to develop new strategies to prevent complications of PPI use

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“…11,14,15 Several individual (e.g., male gender) and environmental (e.g., smoking, vitamin D deficiency, NSAID use, PPI use) risk factors have been associated with the risk of IBD or its complications. 2,[16][17][18][19][20][21] High vitamin D levels are a known protective factor for both CD and UC. 18 A range of comorbidities, likely due to a common pathogenesis of immune dysregulation, have also been shown to correlate with IBD, including history of autoimmune disease 22,23 and eosinophilia.…”

Section: Introductionmentioning

confidence: 99%

Vitamin D intake is associated with decreased risk of immune checkpoint inhibitor‐induced colitis

Grover

Dougan

Tyan

et al. 2020

Cancer

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BACKGROUND: There is a lack of predictive markers informing on the risk of colitis in patients treated with immune checkpoint inhibitors (ICIs). The aim of this study was to identify potential factors associated with development of ICI colitis. METHODS: We performed a retrospective analysis of melanoma patients at Dana-Farber Cancer Institute who received PD-1, CTLA-4, or combination ICIs between May 2011 to October 2017. Clinical and laboratory characteristics associated with pathologically confirmed ICI colitis were evaluated using multivariable logistic regression analyses. External confirmation was performed on an independent cohort from Massachusetts General Hospital. RESULTS: The discovery cohort included 213 patients of whom 37 developed ICI colitis (17%). Vitamin D use was recorded in 66/213 patients (31%) before starting ICIs. In multivariable regression analysis, vitamin D use conferred significantly reduced odds of developing ICI colitis (OR 0.35, 95% CI 0.1-0.9). These results were also demonstrated in the confirmatory cohort (OR 0.46, 95% CI 0.2-0.9) of 169 patients of whom 49 developed ICI colitis (29%). Pre-treatment neutrophil-to-lymphocyte ratio (NLR) ≥5 predicted reduced odds of colitis (OR 0.34, 95% CI 0.1-0.9) only in the discovery cohort. CONCLUSIONS: This is the first study to report that among patients treated with ICIs, vitamin D intake is associated with reduced risk for ICI colitis. This finding is consistent with prior reports of prophylactic use of vitamin D in ulcerative colitis and graft-versus-host-disease. This observation should be validated prospectively in future studies.

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Gastric Acid Suppression Is Associated with an Increased Risk of Adverse Outcomes in Inflammatory Bowel Disease

Cited by 46 publications

References 15 publications

Proton pump inhibitors and dysbiosis: Current knowledge and aspects to be clarified

Proton pump inhibitors and dysbiosis: Current knowledge and aspects to be clarified

Intestinal Dysbiosis Secondary to Proton-Pump Inhibitor Use

Vitamin D intake is associated with decreased risk of immune checkpoint inhibitor‐induced colitis

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