Antibiotics and Inflammatory Bowel Diseases

Scribano, Maria Lia; Prantera, Cosimo

doi:10.1159/000354704

Cited by 24 publications

(14 citation statements)

References 52 publications

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“…Changes in microbial composition induced by antibiotic treatment established a disease course with recurrent inflammation, similar to observations in patients with IBD. 43 The clinical efficacy of microbial therapy in CD, including antibiotics, probiotics and FMT is not well established. Meta-analyses show no clear advantage of probiotics in maintenance of remission in patients with CD, but hint towards a beneficial effect of antibiotics.…”

Section: Discussionmentioning

confidence: 99%

Dysbiotic gut microbiota causes transmissible Crohn's disease-like ileitis independent of failure in antimicrobial defence

Schaubeck

Clavel

Ćalasan

et al. 2015

Gut

361

280

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ObjectivesDysbiosis of the intestinal microbiota is associated with Crohn's disease (CD). Functional evidence for a causal role of bacteria in the development of chronic small intestinal inflammation is lacking. Similar to human pathology, TNFdeltaARE mice develop a tumour necrosis factor (TNF)-driven CD-like transmural inflammation with predominant ileal involvement.DesignHeterozygous TNFdeltaARE mice and wildtype (WT) littermates were housed under conventional (CONV), specific pathogen-free (SPF) and germ-free (GF) conditions. Microbial communities were analysed by high-throughput 16S ribosomal RNA gene sequencing. Metaproteomes were measured using LC-MS. Temporal and spatial resolution of disease development was followed after antibiotic treatment and transfer of microbial communities into GF mice. Granulocyte infiltration and Paneth cell function was assessed by immunofluorescence and gene expression analysis.ResultsGF-TNFdeltaARE mice were free of inflammation in the gut and antibiotic treatment of CONV-TNFdeltaARE mice attenuated ileitis but not colitis, demonstrating that disease severity and location are microbiota-dependent. SPF-TNFdeltaARE mice developed distinct ileitis-phenotypes associated with gradual loss of antimicrobial defence. 16S analysis and metaproteomics revealed specific compositional and functional alterations of bacterial communities in inflamed mice. Transplantation of disease-associated but not healthy microbiota transmitted CD-like ileitis to GF-TNFdeltaARE recipients and triggered loss of lysozyme and cryptdin-2 expression. Monoassociation of GF-TNFdeltaARE mice with the human CD-related Escherichia coli LF82 did not induce ileitis.ConclusionsWe provide clear experimental evidence for the causal role of gut bacterial dysbiosis in the development of chronic ileal inflammation with subsequent failure of Paneth cell function.

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Section: Discussionmentioning

confidence: 99%

Dysbiotic gut microbiota causes transmissible Crohn's disease-like ileitis independent of failure in antimicrobial defence

Schaubeck

Clavel

Ćalasan

et al. 2015

Gut

361

280

View full text Add to dashboard Cite

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“…Therapeutic manipulation of the microbiome can also be achieved through the administration of select antibiotics. In several human studies, metronidazole was associated with disease remission in patients with Crohn's disease . Metronidazole is a nitroimidazole antibiotic and antiprotozoal that is commonly used in small animals with acute and chronic gastrointestinal disorders.…”

Section: Therapeutic Manipulation Of the Gastrointestinal Microbiomementioning

confidence: 99%

The Gastrointestinal Microbiome: A Review

Barko

McMichael

Swanson

et al. 2017

Veterinary Internal Medicne

507

382

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The gastrointestinal microbiome is a diverse consortium of bacteria, archaea, fungi, protozoa, and viruses that inhabit the gut of all mammals. Studies in humans and other mammals have implicated the microbiome in a range of physiologic processes that are vital to host health including energy homeostasis, metabolism, gut epithelial health, immunologic activity, and neurobehavioral development. The microbial genome confers metabolic capabilities exceeding those of the host organism alone, making the gut microbiome an active participant in host physiology. Recent advances in DNA sequencing technology and computational biology have revolutionized the field of microbiomics, permitting mechanistic evaluation of the relationships between an animal and its microbial symbionts. Changes in the gastrointestinal microbiome are associated with diseases in humans and animals including inflammatory bowel disease, asthma, obesity, metabolic syndrome, cardiovascular disease, immune‐mediated conditions, and neurodevelopmental conditions such as autism spectrum disorder. While there remains a paucity of data regarding the intestinal microbiome in small animals, recent studies have helped to characterize its role in host animal health and associated disease states. This review is intended to familiarize small animal veterinarians with recent advances in the field of microbiomics and to prime them for a future in which diagnostic tests and therapies will incorporate these developments into clinical practice.

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“…Unfortunately, this historic use of antibiotics has relatively weak support by large randomized, placebo-controlled trials [22,23]. Several meta-analyses uphold a role for antibiotics in treating both Crohn’s disease and ulcerative colitis [24,25] and antibiotics are universally accepted as the primary treatment of pouchitis.…”

Section: Antibiotics As Primary and Adjunctive Treatmentmentioning

confidence: 99%

Therapeutic Manipulation of the Microbiome in IBD: Current Results and Future Approaches

Hansen

Sartor

2015

Curr Treat Options Gastro

103

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Opinion Statement Despite recent major strides in our understanding of the genetic and microbial influences that contribute to the development of the inflammatory bowel diseases (IBDs), their etiology continues to be enigmatic. Results from experiments in animal models of IBDs overwhelmingly support a causal role of the microbiota in these diseases, though whether such a cause-effect relationship exists in human IBDs is still uncertain. Therefore, virtually all currently-approved, and most often prescribed, treatments for IBDs are directed toward the over-active immune response in these diseases rather than the intestinal bacteria. Nevertheless, there is an important need for non-immunosuppressive therapies that may present a more favorable risk-benefit profile such as those that selectively target the disruptions in gut microbiota that accompany IBDs. This need has led to clinical trials of various microbial-directed therapies including fecal microbial transplant, antibiotics, probiotics, and prebiotics. Unfortunately, these published studies, many of which are small, have generally failed to demonstrate a consistent benefit of these agents in IBDs, thus leading to slow acceptance of microbe-focused treatments for these conditions. In this article, we review and summarize the microbial basis for IBDs and the results of the most recent trials of fecal microbial transplant, antibiotics, probiotics, and prebiotics in IBDs. We also comment on possible safety concerns with these agents, speculate on why they have failed to show efficacy in certain clinical settings, and propose strategies to improve their usefulness.

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Antibiotics and Inflammatory Bowel Diseases

Cited by 24 publications

References 52 publications

Dysbiotic gut microbiota causes transmissible Crohn's disease-like ileitis independent of failure in antimicrobial defence

Dysbiotic gut microbiota causes transmissible Crohn's disease-like ileitis independent of failure in antimicrobial defence

The Gastrointestinal Microbiome: A Review

Therapeutic Manipulation of the Microbiome in IBD: Current Results and Future Approaches

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