Maria Manuela Estevinho1, Cátia Rocha2, Luís Correia3, Paula Lago4, Paula Ministro5, Francisco Portela6, Eunice Trindade7, Joana Afonso8, Laurent Peyrin-Biroulet9, Fernando Magro10. 1. Department of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal; Department of Gastroenterology, Centro Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal. 2. Department of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal; Faculty of Medicine, University of Porto, Porto, Portugal; Instituto de Saúde Ambiental, Faculty of Medicine, University of Porto, Porto, Portugal. 3. Department of Gastroenterology and Hepatology, Hospital de Santa Maria, University of Lisbon, Lisbon, Portugal. 4. Department of Gastroenterology, Centro Hospitalar do Porto, Porto, Portugal. 5. Department of Gastroenterology, Centro Hospitalar Tondela-Viseu, Viseu, Portugal. 6. Centro Hospitalar, Universitário de Coimbra, Coimbra, Portugal. 7. Department of Paediatrics, Centro Hospitalar São João, Porto, Portugal. 8. Department of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal. 9. Institut National de la Sante et de la Recherche Médicale U954, Department of Gastroenterology, Nancy University Hospital, Lorraine University, Nancy, France. 10. Department of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal; Department of Gastroenterology, Centro Hospitalar São João, Porto, Portugal; Center for Drug Discovery and Innovative Medicines (MedInUP), Porto, Portugal. Electronic address: fm@med.up.pt.
Abstract
BACKGROUND & AIMS: We performed a systematic review of changes in fecal and colon microbiomes of patients with inflammatory bowel diseases (IBDs) receiving treatment with monoclonal antibodies against tumor necrosis factor, integrins, or cytokines. We explored associations among microbiome composition and functions (at baseline and throughout the treatment) and therapy-related outcomes to determine whether colon or fecal microbiomes might be used as biomarkers of response to therapy. METHODS: We searched the PubMed, Web of Science, and Science Direct databases through February 2019 for studies of associations among the microbiomes of fecal or colon samples, biologic therapies, and IBDs. We used the critical appraisal skills program checklist to assess the quality of the study methods. RESULTS: From the 787 citations identified, 10 studies met the inclusion criteria. Changes in microbiomes of fecal or colon samples after treatment did not differ significantly among biologic agents; all produced decreases in relative abundances of Escherichia and Enterococcus and increases in genera that produce short-chain fatty acids. Fecal or colon microbiomes of patients who responded to therapy with antagonists of tumor necrosis factor or interleukins had higher α-diversity and increased relative abundances of different genera (Faecalibacterium, Roseburia, or Clostridium) from the Clostridiales order, either at baseline or during follow-up evaluation. Patients in remission after treatment with antibodies against integrins had decreased abundances of Roseburia. CONCLUSIONS: In a systematic review of 10 studies, we found evidence for consistent changes in microbiomes of fecal and colon samples from patients with IBD who responded to treatment with biologic agents. Prospective studies are needed to determine what changes are associated significantly with treatment, whether these changes are causes or effects of response, or whether the composition of the intestinal microbiome can be used to select treatments for patients with IBD.
BACKGROUND & AIMS: We performed a systematic review of changes in fecal and colon microbiomes of patients with inflammatory bowel diseases (IBDs) receiving treatment with monoclonal antibodies against tumor necrosis factor, integrins, or cytokines. We explored associations among microbiome composition and functions (at baseline and throughout the treatment) and therapy-related outcomes to determine whether colon or fecal microbiomes might be used as biomarkers of response to therapy. METHODS: We searched the PubMed, Web of Science, and Science Direct databases through February 2019 for studies of associations among the microbiomes of fecal or colon samples, biologic therapies, and IBDs. We used the critical appraisal skills program checklist to assess the quality of the study methods. RESULTS: From the 787 citations identified, 10 studies met the inclusion criteria. Changes in microbiomes of fecal or colon samples after treatment did not differ significantly among biologic agents; all produced decreases in relative abundances of Escherichia and Enterococcus and increases in genera that produce short-chain fatty acids. Fecal or colon microbiomes of patients who responded to therapy with antagonists of tumor necrosis factor or interleukins had higher α-diversity and increased relative abundances of different genera (Faecalibacterium, Roseburia, or Clostridium) from the Clostridiales order, either at baseline or during follow-up evaluation. Patients in remission after treatment with antibodies against integrins had decreased abundances of Roseburia. CONCLUSIONS: In a systematic review of 10 studies, we found evidence for consistent changes in microbiomes of fecal and colon samples from patients with IBD who responded to treatment with biologic agents. Prospective studies are needed to determine what changes are associated significantly with treatment, whether these changes are causes or effects of response, or whether the composition of the intestinal microbiome can be used to select treatments for patients with IBD.
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