Variable alterations of the microbiota, without metabolic or immunological change, following faecal microbiota transplantation in patients with chronic pouchitis

J Landy; A W Walker; J V Li; H O Al-Hassi; E Ronde; N R English; E R Mann; D Bernardo; S D McLaughlin; J Parkhill; P J Ciclitira; S K Clark; S C Knight; A L Hart

doi:10.1038/srep12955

Variable alterations of the microbiota, without metabolic or immunological change, following faecal microbiota transplantation in patients with chronic pouchitis

J Landy, A W Walker, J V Li, H O Al-Hassi, E Ronde, N R English, E R Mann, D Bernardo, S D McLaughlin, J Parkhill, P J Ciclitira, S K Clark, S C Knight, A L Hart

The Rowett Institute of Nutrition and Health

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Abstract

Faecal microbiota transplantation (FMT) is effective in the treatment of Clostridium difficile infection, where efficacy correlates with changes in microbiota diversity and composition. The effects of FMT on recipient microbiota in inflammatory bowel diseases (IBD) remain unclear. We assessed the effects of FMT on microbiota composition and function, mucosal immune response, and clinical outcome in patients with chronic pouchitis. Eight patients with chronic pouchitis (current PDAI ≥7) were treated with FMT via nasogastric administration. Clinical activity was assessed before and four weeks following FMT. Faecal coliform antibiotic sensitivities were analysed, and changes in pouch faecal and mucosal microbiota assessed by 16S rRNA gene pyrosequencing and (1)H NMR spectroscopy. Lamina propria dendritic cell phenotype and cytokine profiles were assessed by flow cytometric analysis and multiplex assay. Following FMT, there were variable shifts in faecal and mucosal microbiota composition and, in some patients, changes in proportional abundance of species suggestive of a "healthier" pouch microbiota. However, there were no significant FMT-induced metabolic or immunological changes, or beneficial clinical response. Given the lack of clinical response following FMT via a single nasogastric administration our results suggest that FMT/bacteriotherapy for pouchitis patients requires further optimisation.

Original language	English
Article number	12955
Number of pages	10
Journal	Scientific Reports
Volume	5
DOIs	https://doi.org/10.1038/srep12955
Publication status	Published - 12 Aug 2015

Bibliographical note

The authors wish to thank Paul Scott for technical assistance and The Wellcome Trust Sanger Institute’s core sequencing teams for generating the 16S rRNA gene pyrosequencing data. We also wish to thank Dr Louise Bourdon and the Kennedy Galton Centre for assistance with PCR work for this study.

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Alan Walker
- School of Medicine, Medical Sciences & Nutrition, The Rowett Institute of Nutrition and Health - Personal Chair
Person: Academic

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Landy, J., Walker, A. W., Li, J. V., Al-Hassi, H. O., Ronde, E., English, N. R., Mann, E. R., Bernardo, D., McLaughlin, S. D., Parkhill, J., Ciclitira, P. J., Clark, S. K., Knight, S. C., & Hart, A. L. (2015). Variable alterations of the microbiota, without metabolic or immunological change, following faecal microbiota transplantation in patients with chronic pouchitis. Scientific Reports, 5, Article 12955. https://doi.org/10.1038/srep12955

Landy, J, Walker, AW, Li, JV, Al-Hassi, HO, Ronde, E, English, NR, Mann, ER, Bernardo, D, McLaughlin, SD, Parkhill, J, Ciclitira, PJ, Clark, SK, Knight, SC & Hart, AL 2015, 'Variable alterations of the microbiota, without metabolic or immunological change, following faecal microbiota transplantation in patients with chronic pouchitis', Scientific Reports, vol. 5, 12955. https://doi.org/10.1038/srep12955

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abstract = "Faecal microbiota transplantation (FMT) is effective in the treatment of Clostridium difficile infection, where efficacy correlates with changes in microbiota diversity and composition. The effects of FMT on recipient microbiota in inflammatory bowel diseases (IBD) remain unclear. We assessed the effects of FMT on microbiota composition and function, mucosal immune response, and clinical outcome in patients with chronic pouchitis. Eight patients with chronic pouchitis (current PDAI ≥7) were treated with FMT via nasogastric administration. Clinical activity was assessed before and four weeks following FMT. Faecal coliform antibiotic sensitivities were analysed, and changes in pouch faecal and mucosal microbiota assessed by 16S rRNA gene pyrosequencing and (1)H NMR spectroscopy. Lamina propria dendritic cell phenotype and cytokine profiles were assessed by flow cytometric analysis and multiplex assay. Following FMT, there were variable shifts in faecal and mucosal microbiota composition and, in some patients, changes in proportional abundance of species suggestive of a {"}healthier{"} pouch microbiota. However, there were no significant FMT-induced metabolic or immunological changes, or beneficial clinical response. Given the lack of clinical response following FMT via a single nasogastric administration our results suggest that FMT/bacteriotherapy for pouchitis patients requires further optimisation.",

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AU - Al-Hassi, H O

AU - Ronde, E

AU - English, N R

AU - Mann, E R

AU - Bernardo, D

AU - McLaughlin, S D

AU - Parkhill, J

AU - Ciclitira, P J

AU - Clark, S K

AU - Knight, S C

AU - Hart, A L

N1 - The authors wish to thank Paul Scott for technical assistance and The Wellcome Trust Sanger Institute’s core sequencing teams for generating the 16S rRNA gene pyrosequencing data. We also wish to thank Dr Louise Bourdon and the Kennedy Galton Centre for assistance with PCR work for this study.

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N2 - Faecal microbiota transplantation (FMT) is effective in the treatment of Clostridium difficile infection, where efficacy correlates with changes in microbiota diversity and composition. The effects of FMT on recipient microbiota in inflammatory bowel diseases (IBD) remain unclear. We assessed the effects of FMT on microbiota composition and function, mucosal immune response, and clinical outcome in patients with chronic pouchitis. Eight patients with chronic pouchitis (current PDAI ≥7) were treated with FMT via nasogastric administration. Clinical activity was assessed before and four weeks following FMT. Faecal coliform antibiotic sensitivities were analysed, and changes in pouch faecal and mucosal microbiota assessed by 16S rRNA gene pyrosequencing and (1)H NMR spectroscopy. Lamina propria dendritic cell phenotype and cytokine profiles were assessed by flow cytometric analysis and multiplex assay. Following FMT, there were variable shifts in faecal and mucosal microbiota composition and, in some patients, changes in proportional abundance of species suggestive of a "healthier" pouch microbiota. However, there were no significant FMT-induced metabolic or immunological changes, or beneficial clinical response. Given the lack of clinical response following FMT via a single nasogastric administration our results suggest that FMT/bacteriotherapy for pouchitis patients requires further optimisation.

AB - Faecal microbiota transplantation (FMT) is effective in the treatment of Clostridium difficile infection, where efficacy correlates with changes in microbiota diversity and composition. The effects of FMT on recipient microbiota in inflammatory bowel diseases (IBD) remain unclear. We assessed the effects of FMT on microbiota composition and function, mucosal immune response, and clinical outcome in patients with chronic pouchitis. Eight patients with chronic pouchitis (current PDAI ≥7) were treated with FMT via nasogastric administration. Clinical activity was assessed before and four weeks following FMT. Faecal coliform antibiotic sensitivities were analysed, and changes in pouch faecal and mucosal microbiota assessed by 16S rRNA gene pyrosequencing and (1)H NMR spectroscopy. Lamina propria dendritic cell phenotype and cytokine profiles were assessed by flow cytometric analysis and multiplex assay. Following FMT, there were variable shifts in faecal and mucosal microbiota composition and, in some patients, changes in proportional abundance of species suggestive of a "healthier" pouch microbiota. However, there were no significant FMT-induced metabolic or immunological changes, or beneficial clinical response. Given the lack of clinical response following FMT via a single nasogastric administration our results suggest that FMT/bacteriotherapy for pouchitis patients requires further optimisation.

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Variable alterations of the microbiota, without metabolic or immunological change, following faecal microbiota transplantation in patients with chronic pouchitis

Abstract

Bibliographical note

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