Patterns of Antibiotic Exposure and Clinical Disease Activity in Inflammatory Bowel Disease

Hashash, Jana G.; Chintamaneni, Preethi; Rivers, Claudia M. Ramos; Koutroubakis, Ioannis E.; Regueiro, Miguel; Baidoo, Leonard; Swoger, Jason M.; Barrie, Arthur; Schwartz, Marc; Dunn, Michael A.; Binion, David G.

doi:10.1097/mib.0000000000000534

Cited by 13 publications

(4 citation statements)

References 42 publications

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“…These findings suggest that antibiotic-induced dysbiosis of colon microbiota can modulate the immune response in the gut. Consistent with our findings a recent prospective observational study [89] reported that antibiotic exposure over the 4-year study period in patients with IBD for both IBD and non-IBD-related reasons is associated with the more severe clinical presentation. Antibiotic-exposed patients have an elevated rate of C-reactive protein compared with nonantibiotic-exposed patients, which indicates increased inflammation.…”

Section: Discussionsupporting

confidence: 93%

The long-term consequences of antibiotic therapy: Role of colonic short-chain fatty acids (SCFA) system and intestinal barrier integrity

Holota

Dovbynchuk

Kaji³

et al. 2019

PLoS ONE

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Epidemiological studies revealed that antibiotics exposure increases a risk of inflammatory bowel diseases (IBD) development. It remained largely unknown how antibiotic-induced dysbiosis confers the risk for enhanced inflammatory response. The aim of the present study was to test the hypothesis that SCFAs, their receptors and transporters mediate the antibiotic long-term effects on the functional state of colonic mucosa and susceptibility to the experimental colitis. Male Wistar rats were treated daily for 14 days with antibiotic ceftriaxone (300 mg/kg, i.m.) or vehicle; euthanized by CO 2 inhalation followed by cervical dislocation in 1, 14 or 56 days after antibiotic withdrawal. We found increased cecum weight and sustained changes in microbiota composition after ceftriaxone treatment with increased number of conditionally pathogenic enterobacteria, E . coli , Clostridium , Staphylococcus spp . and hemolytic bacteria even at 56 days after antibiotic withdrawal. The concentration of SCFAs was decreased after ceftriaxone withdrawal. We found decreased immunoreactivity of the FFA2, FFA3 receptors, SMCT1 and increased MCT1 & MCT4 transporters of SCFAs in colon mucosa. These changes evoked a significant shift in colonic mucosal homeostasis: the disturbance of oxidant-antioxidant balance; activation of redox-sensitive transcription factor HIF1α and ERK1/2 MAP kinase; increased colonic epithelial permeability and bacterial translocation to blood; morphological remodeling of the colonic tissue. Ceftriaxone pretreatment significantly reinforced inflammation during experimental colitis 56 days after ceftriaxone withdrawal, which was confirmed by increased histopathology of colitis, Goblet cell dysfunction, colonic dilatation and wall thickening, and increased serum levels of inflammatory cytokines (TNF-α and IL-10). Since the recognition of the importance of microbiota metabolic activity rather than their composition in the development of inflammatory disorders, e.g. IBD, the present study is the first report on the role of the SCFA system in the long lasting side effects of antibiotic treatment and its implication in IBD development.

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Section: Discussionsupporting

confidence: 93%

The long-term consequences of antibiotic therapy: Role of colonic short-chain fatty acids (SCFA) system and intestinal barrier integrity

Holota

Dovbynchuk

Kaji³

et al. 2019

PLoS ONE

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“…In line with the concept that a reduced abundance and the loss of certain taxa may be the consequence of antibiotic exposure, a recently published meta-analysis [60] demonstrated that an exposure to antibiotics appears to increase the odds of diagnosing CD but not UC. In addition, there is some evidence that the need for antibiotic treatment in IBD is associated with more severe disease course [61]. Although being plausible that short- and long-term changes in the composition of normal human microbiota affect the susceptibility and course of IBD, a causal relationship between antibiotic-induced dysbiosis and the development of IBD has not been proven yet.…”

Section: Antibiotics - Friend or Foe In The Pathogenesis And Course Omentioning

confidence: 99%

Effects of Antibiotics on Gut Microbiota

Lange

Buerger²,

Stallmach³

et al. 2016

Dig Dis

480

311

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The gut microbiota influences essential human functions including digestion, energy metabolism, and inflammation by modulating multiple endocrine, neural, and immune pathways of the host. Its composition and complexity varies markedly across individuals and across different sites of the gut, but provides a certain level of resilience against external perturbation. Short-term antibiotic treatment is able to shift the gut microbiota to long-term alternative dysbiotic states, which may promote the development and aggravation of disease. Common features of post-antibiotic dysbiosis include a loss of taxonomic and functional diversity combined with reduced colonization resistance against invading pathogens, which harbors the danger of antimicrobial resistance. This review summarizes the antibiotic-related changes of the gut microbiota and potential consequences in health and disease.

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“…New research is focusing on the evaluation of the effectiveness of biological therapies within our patient cohort. We are also dedicating research efforts on quality of care metrics including the management of surveillance colonoscopies in patients with colonic IBD, infection rates, medication exposure, and the frequency and outcomes related to micronutrient repletion [40, 41]. Furthermore, the infrastructure currently afforded by this registry allows application of machine learning algorithms to discover patterns in the data.…”

Section: Discussionmentioning

confidence: 99%

Development of an Inflammatory Bowel Disease Research Registry Derived from Observational Electronic Health Record Data for Comprehensive Clinical Phenotyping

et al. 2016

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Background Inflammatory bowel disease (IBD) is a heterogeneous collection of chronic inflammatory disorders of the digestive tract. Clinical, genetic, and pathological heterogeneity makes it increasingly difficult to translate efficacy studies into real-world practice. Our objective was to develop a comprehensive natural history registry derived from multi-year observational data to facilitate effectiveness and clinical phenotypic research in IBD. Methods A longitudinal, consented registry with prospectively collected data was developed at UPMC. All adult IBD patients receiving care at the tertiary care center of UPMC are eligible for enrollment. Detailed data in the electronic health record are accessible for registry research purposes. Data are exported directly from the electronic health record and temporally organized for research. Results To date, there are over 2565 patients participating in the IBD research registry. All patients have demographic data, clinical disease characteristics, and disease course data including healthcare utilization, laboratory values, health-related questionnaires quantifying disease activity and quality of life, and analytical information on treatment, temporally organized for 6 years (2009–2015). The data have resulted in a detailed definition of clinical phenotypes suitable for association studies with parameters of disease outcomes and treatment response. We have established the infrastructure required to examine the effectiveness of treatment and disease course in the real-world setting of IBD. Conclusions The IBD research registry offers a unique opportunity to investigate clinical research questions regarding the natural course of the disease, phenotype association studies, effectiveness of treatment, and quality of care research.

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Patterns of Antibiotic Exposure and Clinical Disease Activity in Inflammatory Bowel Disease

Abstract: The majority of patients with IBD receive antibiotic treatment, and these individuals demonstrate a more severe clinical course.

Cited by 13 publications

References 42 publications

The long-term consequences of antibiotic therapy: Role of colonic short-chain fatty acids (SCFA) system and intestinal barrier integrity

The long-term consequences of antibiotic therapy: Role of colonic short-chain fatty acids (SCFA) system and intestinal barrier integrity

Effects of Antibiotics on Gut Microbiota

Development of an Inflammatory Bowel Disease Research Registry Derived from Observational Electronic Health Record Data for Comprehensive Clinical Phenotyping

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