Gut Microbiota Composition Before and After Use of Proton Pump Inhibitors

Hojo, Mariko; Asahara, Takashi; Nagahara, Akihito; Takeda, Tsutomu; Matsumoto, Keīichi; Ueyama, Hiroya; Matsumoto, Kenshi; Asaoka, Daisuke; Takahashi, Takuya; Nomoto, Koji; Yamashiro, Yuichiro; Watanabe, Sumio

doi:10.1007/s10620-018-5122-4

Cited by 82 publications

(82 citation statements)

References 60 publications

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“…These results have been replicated in subsequent studies 41,42 . To the best of our knowledge, this is the first study which has assessed the effect of PPI on the small intestinal bacterial load utilising qPCR, with the majority of previous studies focusing on stool samples 43‐45 and/or samples from the oral cavity 40,46 . Thus, our data provide further evidence that PPI therapy is associated with a small intestinal “dysbiosis” but expands this concept to variations in bacterial load on tissue.…”

Section: Discussionsupporting

confidence: 62%

Duodenal bacterial load as determined by quantitative polymerase chain reaction in asymptomatic controls, functional gastrointestinal disorders and inflammatory bowel disease

Shah

Talley

Koloski

et al. 2020

Aliment Pharmacol Ther

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Summary Background Small intestinal bacterial overgrowth may play a role in gastrointestinal and non‐gastrointestinal diseases. Aims To use quantitative polymerase chain reaction (qPCR) to determine and compare bacterial loads of duodenal biopsies in asymptomatic controls, and patients with functional gastrointestinal disorders (FGIDs) and inflammatory bowel disease (IBD) including ulcerative colitis (UC) and Crohn’s disease (CD). To define effects of gastric acid inhibition on bacterial load, explore links of bacterial load and gastrointestinal symptoms in response to a standardised nutrient challenge and compare bacterial load with glucose breath test results. Methods In 237 patients (63 controls, 84 FGID and 90 IBD), we collected mucosal samples under aseptic conditions during endoscopy extracted and total DNA. Bacterial load metric was calculated utilising qPCR measurements of the bacterial 16S rRNA gene, normalised to human beta‐actin expression. Standard glucose breath test and nutrient challenge test were performed. Results The duodenal microbial load was higher in patients with FGID (0.22 ± 0.03) than controls (0.07 ± 0.05; P = 0.007) and patients with UC (0.01 ± 0.05) or CD (0.02 ± 0.09), (P = 0.0001). While patients treated with proton pump inhibitors (PPI) had significantly higher bacterial loads than non‐users (P < 0.05), this did not explain differences between patient groups and controls. Bacterial load was significantly (r = 0.21, P < 0.016) associated with the symptom response to standardised nutrient challenge test. Methane, but not hydrogen values on glucose breath test were associated with bacterial load measured utilising qPCR. Conclusions Utilising qPCR, a diagnosis of FGID and treatment with PPI were independently associated with increased bacterial loads. Increased bacterial loads are associated with an augmented symptom response to a standardised nutrient challenge.

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Section: Discussionsupporting

confidence: 62%

Duodenal bacterial load as determined by quantitative polymerase chain reaction in asymptomatic controls, functional gastrointestinal disorders and inflammatory bowel disease

Shah

Talley

Koloski

et al. 2020

Aliment Pharmacol Ther

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“…These studies focused on the concomitant use of these two drugs and showed no influence of PPIs on the pharmacokinetics of NSAIDs [ 45 , 46 ]. However, PPI use might increase the risk of an imbalance in gut microbiota composition, even 8 weeks after PPI treatment [ 47 , 48 ]. This change in microbiota composition has been shown to exacerbate NSAID side effects [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Use of nonsteroidal anti-inflammatory drugs and breast cancer risk in a prospective cohort of postmenopausal women

et al. 2020

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Background Although anti-inflammatory agents could theoretically have anticancer properties, results from cohort studies on nonsteroidal anti-inflammatory drugs (NSAIDs) and breast cancer (BC) risk are inconsistent. Methods We investigated the association between NSAID use and BC incidence in the French E3N prospective cohort, which includes 98,995 women born between 1925 and 1950 and insured by a health insurance plan that covers mostly teachers. Self-reported information on lifestyle and medical history has been collected biennially by questionnaires and matched with data from a drug reimbursement database covering the period 2004–2014. Women who self-reported current NSAID use in the 2000 or 2002 questionnaires or with at least two reimbursements in any previous 3-month period were defined as exposed to NSAIDs. Multivariable Cox regression models were used to estimate hazard ratios (HRs) for the association of NSAID use with BC risk. Results In the current analysis, 62,512 postmenopausal women were followed between 2004 and 2014 (9 years on average, starting at a mean age of 63 years; 2864 incident BC). In multivariable models, there was no statistically significant association between NSAID use and BC risk [HR = 1.00 (0.92–1.08), compared with non-exposed women]. The NSAID-BC associations did not differ by NSAID types, BC subtypes, risk factors, and comorbidities, nor by duration and dose of use. However, a statistically significant interaction was observed by proton pump inhibitor (PPI) drug use (Pinteraction = 0.01) whereby a decreased risk of BC with NSAID use was only observed among women who also used PPI before. Conclusion Only women who used NSAIDs after having used PPI had a lower risk of BC. This result is novel and requires replication in other studies.

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“…PPIs decrease the acidity in the stomach by inhibition of the H + /K + -ATPase enzyme in the parietal cells of the gastric glands. As a consequence, the pH of the proximal intestine is increased [29,32], which can affect the gut microbiome [33,34]. The use of PPIs has also been associated with a decreased absorption of vitamin B 12 , magnesium, calcium, iron, vitamin C, β-carotene, and zinc, which is at least in part a direct consequence of their reduced release from the food matrix and (or) effects on the absorption process [29,[35][36][37][38] At the clinical level, PPI use has been reported as a variable of importance, after gait speed, oxidative stress, and depression, in the prediction of muscle mass and function loss in aging (sarcopenia) [39].…”

Section: Adverse Effects Of Long Term Use Of Ppismentioning

confidence: 99%

“…To conclude, although generally considered safe, long-term use of PPIs could ultimately lead to deficiencies in several vitamins and minerals [36,37,43]. Furthermore, the changed pH can affect the gut microbiome [33,34], and finally, it can result in the presence of myopathy, which might affect muscle function and mass [39].…”

Section: Adverse Effects Of Long Term Use Of Ppismentioning

confidence: 99%

The Use of Proton Pump Inhibitors May Increase Symptoms of Muscle Function Loss in Patients with Chronic Illnesses

Vinke

Wesselink

Orten-Luiten

et al. 2020

IJMS

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Long-term use of proton pump inhibitors (PPIs) is common in patients with muscle wasting-related chronic diseases. We explored the hypothesis that the use of PPIs may contribute to a reduction in muscle mass and function in these patients. Literature indicates that a PPI-induced reduction in acidity of the gastrointestinal tract can decrease the absorption of, amongst others, magnesium. Low levels of magnesium are associated with impaired muscle function. This unwanted side-effect of PPIs on muscle function has been described in different disease backgrounds. Furthermore, magnesium is necessary for activation of vitamin D. Low vitamin D and magnesium levels together can lead to increased inflammation involved in muscle wasting. In addition, PPI use has been described to alter the microbiota’s composition in the gut, which might lead to increased inflammation. However, PPIs are often provided together with nonsteroidal anti-inflammatory drugs (NSAIDs), which are anti-inflammatory. In the presence of obesity, additional mechanisms could further contribute to muscle alterations. In conclusion, use of PPIs has been reported to contribute to muscle function loss. Whether this will add to the risk factor for development of muscle function loss in patients with chronic disease needs further investigation.

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Gut Microbiota Composition Before and After Use of Proton Pump Inhibitors

Cited by 82 publications

References 60 publications

Duodenal bacterial load as determined by quantitative polymerase chain reaction in asymptomatic controls, functional gastrointestinal disorders and inflammatory bowel disease

Duodenal bacterial load as determined by quantitative polymerase chain reaction in asymptomatic controls, functional gastrointestinal disorders and inflammatory bowel disease

Use of nonsteroidal anti-inflammatory drugs and breast cancer risk in a prospective cohort of postmenopausal women

The Use of Proton Pump Inhibitors May Increase Symptoms of Muscle Function Loss in Patients with Chronic Illnesses

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