Bacterial clade-specific analysis identifies distinct epithelial responses in inflammatory bowel disease

Gemma L. D'Adamo; Michelle Chonwerawong; Linden J. Gearing; Vanessa R. Marcelino; Jodee A. Gould; Emily L. Rutten; Sean M. Solari; Patricia W.R. Khoo; Trevor J. Wilson; Tamblyn Thomason; Emily L. Gulliver; Paul J. Hertzog; Edward M. Giles; Samuel C. Forster

doi:10.1016/j.xcrm.2023.101124

Bacterial clade-specific analysis identifies distinct epithelial responses in inflammatory bowel disease

Gemma L. D'Adamo, Michelle Chonwerawong, Linden J. Gearing, Vanessa R. Marcelino, Jodee A. Gould, Emily L. Rutten, Sean M. Solari, Patricia W.R. Khoo, Trevor J. Wilson, Tamblyn Thomason, Emily L. Gulliver, Paul J. Hertzog, Edward M. Giles, Samuel C. Forster

Hudson Institute - Department of Molecular and Translational Science

Research output: Contribution to journal › Article › Research › peer-review

5 Citations (Scopus)

Abstract

Abnormal immune responses to the resident gut microbiome can drive inflammatory bowel disease (IBD). Here, we combine high-resolution, culture-based shotgun metagenomic sequencing and analysis with matched host transcriptomics across three intestinal sites (terminal ileum, cecum, rectum) from pediatric IBD (PIBD) patients (n = 58) and matched controls (n = 42) to investigate this relationship. Combining our site-specific approach with bacterial culturing, we establish a cohort-specific bacterial culture collection, comprising 6,620 isolates (170 distinct species, 32 putative novel), cultured from 286 mucosal biopsies. Phylogeny-based, clade-specific metagenomic analysis identifies key, functionally distinct Enterococcus clades associated with either IBD or health. Strain-specific in vitro validation demonstrates differences in cell cytotoxicity and inflammatory signaling in intestinal epithelial cells, consistent with the colonic mucosa-specific response measured in patients with IBD. This demonstrates the importance of strain-specific phenotypes and consideration of anatomical sites in exploring the dysregulated host-bacterial interactions in IBD.

Original language	English
Article number	101124
Number of pages	14
Journal	Cell Reports Medicine
Volume	4
Issue number	7
DOIs	https://doi.org/10.1016/j.xcrm.2023.101124
Publication status	Published - 18 Jul 2023

Keywords

cell death
Enterococcus
epithelial cells
gastrointestinal tract
host-microbe interactions
inflammatory bowel disease
metagenomic
microbiome
pediatric IBD
ulcerative colitis

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10.1016/j.xcrm.2023.101124Licence: CC BY-NC-ND

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D'Adamo, G. L., Chonwerawong, M., Gearing, L. J., Marcelino, V. R., Gould, J. A., Rutten, E. L., Solari, S. M., Khoo, P. W. R., Wilson, T. J., Thomason, T., Gulliver, E. L., Hertzog, P. J., Giles, E. M., & Forster, S. C. (2023). Bacterial clade-specific analysis identifies distinct epithelial responses in inflammatory bowel disease. Cell Reports Medicine, 4(7), Article 101124. https://doi.org/10.1016/j.xcrm.2023.101124

@article{f0da00d552ab4116bfde933219be5ea2,

title = "Bacterial clade-specific analysis identifies distinct epithelial responses in inflammatory bowel disease",

abstract = "Abnormal immune responses to the resident gut microbiome can drive inflammatory bowel disease (IBD). Here, we combine high-resolution, culture-based shotgun metagenomic sequencing and analysis with matched host transcriptomics across three intestinal sites (terminal ileum, cecum, rectum) from pediatric IBD (PIBD) patients (n = 58) and matched controls (n = 42) to investigate this relationship. Combining our site-specific approach with bacterial culturing, we establish a cohort-specific bacterial culture collection, comprising 6,620 isolates (170 distinct species, 32 putative novel), cultured from 286 mucosal biopsies. Phylogeny-based, clade-specific metagenomic analysis identifies key, functionally distinct Enterococcus clades associated with either IBD or health. Strain-specific in vitro validation demonstrates differences in cell cytotoxicity and inflammatory signaling in intestinal epithelial cells, consistent with the colonic mucosa-specific response measured in patients with IBD. This demonstrates the importance of strain-specific phenotypes and consideration of anatomical sites in exploring the dysregulated host-bacterial interactions in IBD.",

keywords = "cell death, Enterococcus, epithelial cells, gastrointestinal tract, host-microbe interactions, inflammatory bowel disease, metagenomic, microbiome, pediatric IBD, ulcerative colitis",

author = "D'Adamo, {Gemma L.} and Michelle Chonwerawong and Gearing, {Linden J.} and Marcelino, {Vanessa R.} and Gould, {Jodee A.} and Rutten, {Emily L.} and Solari, {Sean M.} and Khoo, {Patricia W.R.} and Wilson, {Trevor J.} and Tamblyn Thomason and Gulliver, {Emily L.} and Hertzog, {Paul J.} and Giles, {Edward M.} and Forster, {Samuel C.}",

note = "Funding Information: This work was supported by the Australian National Health and Medical Research Council grants 1159239 (S.C.F.), 1181105 (S.C.F. E.M.G.), and 1186371 (S.C.F. P.J.H.); the Australian Research Council DP190101504 (S.C.F.) and DE220100965 (V.R.M.); the Walter Cottman Endowment Fund (E.M.G. S.C.F.); the Gastroenterological Society of Australia (E.M.G. S.C.F.); and the Kenneth Rainin Foundation (E.M.G. S.C.F.). S.C.F. is supported by a CSL Centenary Fellowship. The authors would also like to acknowledge the clinical staff in endoscopy at Monash Children's Hospital, the patients and parents that kindly consented to contribute to the study, the Monash eResearch Team, the Ramaciotti Centre for Cryo-Electron Microscopy (Monash University), the CSIRO UROP Program, Prof. Kim-Anh Le Cao, and the support of the Victorian State Government Operational Infrastructure Scheme. Funding for the open-access charge was provided by Monash University. Conceptualization, S.C.F. E.M.G. and G.L.D.; methodology, G.L.D. S.C.F. E.M.G. M.C. J.A.G. T.J.W. and P.J.H.; investigation, G.L.D. M.C. E.L.R. T.T. J.A.G. and P.W.R.K.; data curation: G.L.D. L.J.G. S.M.S. and V.R.M.; formal analysis: G.L.D. L.J.G. S.M.S. V.R.M. and S.C.F.; writing – original draft, G.L.D. S.C.F. and E.M.G.; writing – review & editing, G.L.D. S.C.F. E.M.G. M.C. L.J.G. V.R.M. J.A.G. E.L.R. S.M.S. P.W.R.K. T.J.W. T.T. E.L.G. and P.J.H.; project administration, G.L.D. E.M.G. and S.C.F.; supervision, S.C.F. E.M.G. and P.J.H.; funding acquisition, S.C.F. E.M.G and P.J.H. We have filed a patent related to this work (WO2021163758). S.C.F. has acted as a scientific advisor to Microbiotica and Biomebank Australia. We worked to ensure gender balance in the recruitment of human subjects. We worked to ensure ethnic or other types of diversity in the recruitment of human subjects. We worked to ensure that the study questionnaires were prepared in an inclusive way. Funding Information: This work was supported by the Australian National Health and Medical Research Council grants 1159239 (S.C.F.), 1181105 (S.C.F., E.M.G.), and 1186371 (S.C.F., P.J.H.); the Australian Research Council DP190101504 (S.C.F.) and DE220100965 (V.R.M.); the Walter Cottman Endowment Fund (E.M.G., S.C.F.); the Gastroenterological Society of Australia (E.M.G., S.C.F.); and the Kenneth Rainin Foundation (E.M.G., S.C.F.). S.C.F. is supported by a CSL Centenary Fellowship. The authors would also like to acknowledge the clinical staff in endoscopy at Monash Children{\textquoteright}s Hospital , the patients and parents that kindly consented to contribute to the study, the Monash eResearch Team , the Ramaciotti Centre for Cryo-Electron Microscopy ( Monash University ), the CSIRO UROP Program, Prof. Kim-Anh Le Cao, and the support of the Victorian State Government Operational Infrastructure Scheme . Funding for the open-access charge was provided by Monash University . Publisher Copyright: {\textcopyright} 2023 The Author(s)",

year = "2023",

month = jul,

day = "18",

doi = "10.1016/j.xcrm.2023.101124",

language = "English",

volume = "4",

journal = "Cell Reports Medicine",

issn = "2666-3791",

publisher = "Cell Press",

number = "7",

}

D'Adamo, GL, Chonwerawong, M, Gearing, LJ, Marcelino, VR, Gould, JA, Rutten, EL, Solari, SM, Khoo, PWR, Wilson, TJ, Thomason, T, Gulliver, EL, Hertzog, PJ, Giles, EM & Forster, SC 2023, 'Bacterial clade-specific analysis identifies distinct epithelial responses in inflammatory bowel disease', Cell Reports Medicine, vol. 4, no. 7, 101124. https://doi.org/10.1016/j.xcrm.2023.101124

TY - JOUR

T1 - Bacterial clade-specific analysis identifies distinct epithelial responses in inflammatory bowel disease

AU - D'Adamo, Gemma L.

AU - Chonwerawong, Michelle

AU - Gearing, Linden J.

AU - Marcelino, Vanessa R.

AU - Gould, Jodee A.

AU - Rutten, Emily L.

AU - Solari, Sean M.

AU - Khoo, Patricia W.R.

AU - Wilson, Trevor J.

AU - Thomason, Tamblyn

AU - Gulliver, Emily L.

AU - Hertzog, Paul J.

AU - Giles, Edward M.

AU - Forster, Samuel C.

N1 - Funding Information: This work was supported by the Australian National Health and Medical Research Council grants 1159239 (S.C.F.), 1181105 (S.C.F. E.M.G.), and 1186371 (S.C.F. P.J.H.); the Australian Research Council DP190101504 (S.C.F.) and DE220100965 (V.R.M.); the Walter Cottman Endowment Fund (E.M.G. S.C.F.); the Gastroenterological Society of Australia (E.M.G. S.C.F.); and the Kenneth Rainin Foundation (E.M.G. S.C.F.). S.C.F. is supported by a CSL Centenary Fellowship. The authors would also like to acknowledge the clinical staff in endoscopy at Monash Children's Hospital, the patients and parents that kindly consented to contribute to the study, the Monash eResearch Team, the Ramaciotti Centre for Cryo-Electron Microscopy (Monash University), the CSIRO UROP Program, Prof. Kim-Anh Le Cao, and the support of the Victorian State Government Operational Infrastructure Scheme. Funding for the open-access charge was provided by Monash University. Conceptualization, S.C.F. E.M.G. and G.L.D.; methodology, G.L.D. S.C.F. E.M.G. M.C. J.A.G. T.J.W. and P.J.H.; investigation, G.L.D. M.C. E.L.R. T.T. J.A.G. and P.W.R.K.; data curation: G.L.D. L.J.G. S.M.S. and V.R.M.; formal analysis: G.L.D. L.J.G. S.M.S. V.R.M. and S.C.F.; writing – original draft, G.L.D. S.C.F. and E.M.G.; writing – review & editing, G.L.D. S.C.F. E.M.G. M.C. L.J.G. V.R.M. J.A.G. E.L.R. S.M.S. P.W.R.K. T.J.W. T.T. E.L.G. and P.J.H.; project administration, G.L.D. E.M.G. and S.C.F.; supervision, S.C.F. E.M.G. and P.J.H.; funding acquisition, S.C.F. E.M.G and P.J.H. We have filed a patent related to this work (WO2021163758). S.C.F. has acted as a scientific advisor to Microbiotica and Biomebank Australia. We worked to ensure gender balance in the recruitment of human subjects. We worked to ensure ethnic or other types of diversity in the recruitment of human subjects. We worked to ensure that the study questionnaires were prepared in an inclusive way. Funding Information: This work was supported by the Australian National Health and Medical Research Council grants 1159239 (S.C.F.), 1181105 (S.C.F., E.M.G.), and 1186371 (S.C.F., P.J.H.); the Australian Research Council DP190101504 (S.C.F.) and DE220100965 (V.R.M.); the Walter Cottman Endowment Fund (E.M.G., S.C.F.); the Gastroenterological Society of Australia (E.M.G., S.C.F.); and the Kenneth Rainin Foundation (E.M.G., S.C.F.). S.C.F. is supported by a CSL Centenary Fellowship. The authors would also like to acknowledge the clinical staff in endoscopy at Monash Children’s Hospital , the patients and parents that kindly consented to contribute to the study, the Monash eResearch Team , the Ramaciotti Centre for Cryo-Electron Microscopy ( Monash University ), the CSIRO UROP Program, Prof. Kim-Anh Le Cao, and the support of the Victorian State Government Operational Infrastructure Scheme . Funding for the open-access charge was provided by Monash University . Publisher Copyright: © 2023 The Author(s)

PY - 2023/7/18

Y1 - 2023/7/18

N2 - Abnormal immune responses to the resident gut microbiome can drive inflammatory bowel disease (IBD). Here, we combine high-resolution, culture-based shotgun metagenomic sequencing and analysis with matched host transcriptomics across three intestinal sites (terminal ileum, cecum, rectum) from pediatric IBD (PIBD) patients (n = 58) and matched controls (n = 42) to investigate this relationship. Combining our site-specific approach with bacterial culturing, we establish a cohort-specific bacterial culture collection, comprising 6,620 isolates (170 distinct species, 32 putative novel), cultured from 286 mucosal biopsies. Phylogeny-based, clade-specific metagenomic analysis identifies key, functionally distinct Enterococcus clades associated with either IBD or health. Strain-specific in vitro validation demonstrates differences in cell cytotoxicity and inflammatory signaling in intestinal epithelial cells, consistent with the colonic mucosa-specific response measured in patients with IBD. This demonstrates the importance of strain-specific phenotypes and consideration of anatomical sites in exploring the dysregulated host-bacterial interactions in IBD.

AB - Abnormal immune responses to the resident gut microbiome can drive inflammatory bowel disease (IBD). Here, we combine high-resolution, culture-based shotgun metagenomic sequencing and analysis with matched host transcriptomics across three intestinal sites (terminal ileum, cecum, rectum) from pediatric IBD (PIBD) patients (n = 58) and matched controls (n = 42) to investigate this relationship. Combining our site-specific approach with bacterial culturing, we establish a cohort-specific bacterial culture collection, comprising 6,620 isolates (170 distinct species, 32 putative novel), cultured from 286 mucosal biopsies. Phylogeny-based, clade-specific metagenomic analysis identifies key, functionally distinct Enterococcus clades associated with either IBD or health. Strain-specific in vitro validation demonstrates differences in cell cytotoxicity and inflammatory signaling in intestinal epithelial cells, consistent with the colonic mucosa-specific response measured in patients with IBD. This demonstrates the importance of strain-specific phenotypes and consideration of anatomical sites in exploring the dysregulated host-bacterial interactions in IBD.

KW - cell death

KW - Enterococcus

KW - epithelial cells

KW - gastrointestinal tract

KW - host-microbe interactions

KW - inflammatory bowel disease

KW - metagenomic

KW - microbiome

KW - pediatric IBD

KW - ulcerative colitis

UR - http://www.scopus.com/inward/record.url?scp=85164980081&partnerID=8YFLogxK

U2 - 10.1016/j.xcrm.2023.101124

DO - 10.1016/j.xcrm.2023.101124

M3 - Article

C2 - 37467722

AN - SCOPUS:85164980081

SN - 2666-3791

VL - 4

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 7

M1 - 101124

ER -

Bacterial clade-specific analysis identifies distinct epithelial responses in inflammatory bowel disease

Abstract

Keywords

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Other files and links

Innate mucosal sensing & shaping of the human-microbiome

Microbiome derived candidates to revolutionise treatment of inflammatory bowel disease

Phenotypic, genomic and informatic characterization of host-microbiota interactions to improve human health

MHTP Medical Genomics Facility

Cite this

Bacterial clade-specific analysis identifies distinct epithelial responses in inflammatory bowel disease

Abstract

Keywords

Access to Document

Other files and links

Projects

Innate mucosal sensing & shaping of the human-microbiome

Microbiome derived candidates to revolutionise treatment of inflammatory bowel disease

Phenotypic, genomic and informatic characterization of host-microbiota interactions to improve human health

Equipment

MHTP Medical Genomics Facility

Cite this