Human Gut Symbiont Roseburia hominis Promotes and Regulates Innate Immunity

Angela M Patterson; Imke E Mulder; Anthony J Travis; Annaig Lan; Nadine Cerf-Bensussan; Valerie Gaboriau-Routhiau; Karen Garden; Elizabeth Logan; Margaret I Delday; Alistair G P Coutts; Edouard Monnais; Vanessa C Ferraria; Ryo Inoue; George Grant; Rustam I Aminov

doi:10.3389/fimmu.2017.01166

Human Gut Symbiont Roseburia hominis Promotes and Regulates Innate Immunity

Angela M Patterson, Imke E Mulder, Anthony J Travis, Annaig Lan, Nadine Cerf-Bensussan, Valerie Gaboriau-Routhiau, Karen Garden, Elizabeth Logan, Margaret I Delday, Alistair G P Coutts, Edouard Monnais, Vanessa C Ferraria, Ryo Inoue, George Grant, Rustam I Aminov

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Abstract

OBJECTIVE: Roseburia hominis is a flagellated gut anaerobic bacterium belonging to the Lachnospiraceae family within the Firmicutes phylum. A significant decrease of R. hominis colonization in the gut of ulcerative colitis patients has recently been demonstrated. In this work, we have investigated the mechanisms of R. hominis-host cross talk using both murine and in vitro models.

DESIGN: The complete genome sequence of R. hominis A2-183 was determined. C3H/HeN germ-free mice were mono-colonized with R. hominis, and the host-microbe interaction was studied using histology, transcriptome analyses and FACS. Further investigations were performed in vitro and using the TLR5KO and DSS-colitis murine models.

RESULTS: In the bacterium, R. hominis, host gut colonization upregulated genes involved in conjugation/mobilization, metabolism, motility, and chemotaxis. In the host cells, bacterial colonization upregulated genes related to antimicrobial peptides, gut barrier function, toll-like receptors (TLR) signaling, and T cell biology. CD4(+)CD25(+)FoxP3(+) T cell numbers increased in the lamina propria of both mono-associated and conventional mice treated with R. hominis. Treatment with the R. hominis bacterium provided protection against DSS-induced colitis. The role of flagellin in host-bacterium interaction was also investigated.

CONCLUSION: Mono-association of mice with R. hominis bacteria results in specific bidirectional gene expression patterns. A set of genes thought to be important for host colonization are induced in R. hominis, while the host cells respond by strengthening gut barrier function and enhancing Treg population expansion, possibly via TLR5-flagellin signaling. Our data reveal the immunomodulatory properties of R. hominis that could be useful for the control and treatment of gut inflammation.

Original language	English
Article number	1166
Pages (from-to)	1-14
Number of pages	14
Journal	Frontiers in Immunology
Volume	8
DOIs	https://doi.org/10.3389/fimmu.2017.01166
Publication status	Published - 26 Sept 2017

Bibliographical note

Acknowledgments
The authors would like to thank Andrew Gewirtz (Georgia State University, Atlanta, GA, USA) and Adam Cunningham (University of Birmingham, Edgbaston, Birmingham, UK) for generously providing the germ-free and conventional TLR5KO mice, respectively. The authors also wish to acknowledge a significant contribution to the inception of the work, experimental work, interpretation of results, and writing of the manuscript by Denise Kelly, as well as the support from RESAS (Rural and Environmental Science and Analytical Services) of the Scottish Government. EM and VF were supported by the Marie Curie Initial training network Fellowships funded by the EU (grant #215532). The authors acknowledge a generous support of Prof. Harry Flint and Dr. Sylvia Duncan in the microbiological part of this work. The skilled technical support of Gillian Campbell and Pauline Young at RINH Genomics is also gratefully acknowledged.

Keywords

Journal Article
Roseburia
T lymphocytes
immune tolerance
inflammatory bowel disease
flagellin
TLR5

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10.3389/fimmu.2017.01166Licence: CC BY

Human Gut Symbiont Roseburia hominis Promotes and Regulates Innate Immunity
© 2017 Patterson, Mulder, Travis, Lan, Cerf-Bensussan, Gaboriau-Routhiau, Garden, Logan, Delday, Coutts, Monnais, Ferraria, Inoue, Grant and Aminov. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. https://creativecommons.org/licenses/by/4.0/
Final published version, 2.47 MBLicence: CC BY

GSE25544 Host/microbial cross-talk in the gut : in-depth investigation of the symbiotic effects of Roseburia hominis
Kelly, D. (Creator), Hooiveld, G. (Creator), Van Iersel, M. (Creator), Koks, P. D. (Creator), Elliott, R. M. (Creator), Rocca-Serra, P. (Creator), Mulder, I. E. (Creator) & Morgan, P. J. (Data Manager), GEO, 5 Feb 2016
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627938 and 36 more links, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627963, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627962, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627959, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627957, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627956, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627952, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627946, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627942, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627943, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627934, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627932, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627928, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627947, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627936, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627929, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627930, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627931, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627937, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627960, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627961, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627954, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627953, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627958, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627955, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627945, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627944, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627940, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627939, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627951, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627950, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627949, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627948, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627941, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627935, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSM627933, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE25544 (show fewer)
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Patterson, A. M., Mulder, I. E., Travis, A. J., Lan, A., Cerf-Bensussan, N., Gaboriau-Routhiau, V., Garden, K., Logan, E., Delday, M. I., Coutts, A. G. P., Monnais, E., Ferraria, V. C., Inoue, R., Grant, G., & Aminov, R. I. (2017). Human Gut Symbiont Roseburia hominis Promotes and Regulates Innate Immunity. Frontiers in Immunology, 8, 1-14. Article 1166. https://doi.org/10.3389/fimmu.2017.01166

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title = "Human Gut Symbiont Roseburia hominis Promotes and Regulates Innate Immunity",

abstract = "OBJECTIVE: Roseburia hominis is a flagellated gut anaerobic bacterium belonging to the Lachnospiraceae family within the Firmicutes phylum. A significant decrease of R. hominis colonization in the gut of ulcerative colitis patients has recently been demonstrated. In this work, we have investigated the mechanisms of R. hominis-host cross talk using both murine and in vitro models.DESIGN: The complete genome sequence of R. hominis A2-183 was determined. C3H/HeN germ-free mice were mono-colonized with R. hominis, and the host-microbe interaction was studied using histology, transcriptome analyses and FACS. Further investigations were performed in vitro and using the TLR5KO and DSS-colitis murine models.RESULTS: In the bacterium, R. hominis, host gut colonization upregulated genes involved in conjugation/mobilization, metabolism, motility, and chemotaxis. In the host cells, bacterial colonization upregulated genes related to antimicrobial peptides, gut barrier function, toll-like receptors (TLR) signaling, and T cell biology. CD4(+)CD25(+)FoxP3(+) T cell numbers increased in the lamina propria of both mono-associated and conventional mice treated with R. hominis. Treatment with the R. hominis bacterium provided protection against DSS-induced colitis. The role of flagellin in host-bacterium interaction was also investigated.CONCLUSION: Mono-association of mice with R. hominis bacteria results in specific bidirectional gene expression patterns. A set of genes thought to be important for host colonization are induced in R. hominis, while the host cells respond by strengthening gut barrier function and enhancing Treg population expansion, possibly via TLR5-flagellin signaling. Our data reveal the immunomodulatory properties of R. hominis that could be useful for the control and treatment of gut inflammation.",

keywords = "Journal Article, Roseburia, T lymphocytes, immune tolerance, inflammatory bowel disease, flagellin, TLR5",

author = "Patterson, {Angela M} and Mulder, {Imke E} and Travis, {Anthony J} and Annaig Lan and Nadine Cerf-Bensussan and Valerie Gaboriau-Routhiau and Karen Garden and Elizabeth Logan and Delday, {Margaret I} and Coutts, {Alistair G P} and Edouard Monnais and Ferraria, {Vanessa C} and Ryo Inoue and George Grant and Aminov, {Rustam I}",

note = "Acknowledgments The authors would like to thank Andrew Gewirtz (Georgia State University, Atlanta, GA, USA) and Adam Cunningham (University of Birmingham, Edgbaston, Birmingham, UK) for generously providing the germ-free and conventional TLR5KO mice, respectively. The authors also wish to acknowledge a significant contribution to the inception of the work, experimental work, interpretation of results, and writing of the manuscript by Denise Kelly, as well as the support from RESAS (Rural and Environmental Science and Analytical Services) of the Scottish Government. EM and VF were supported by the Marie Curie Initial training network Fellowships funded by the EU (grant #215532). The authors acknowledge a generous support of Prof. Harry Flint and Dr. Sylvia Duncan in the microbiological part of this work. The skilled technical support of Gillian Campbell and Pauline Young at RINH Genomics is also gratefully acknowledged.",

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month = sep,

day = "26",

doi = "10.3389/fimmu.2017.01166",

language = "English",

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journal = "Frontiers in Immunology",

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TY - JOUR

T1 - Human Gut Symbiont Roseburia hominis Promotes and Regulates Innate Immunity

AU - Patterson, Angela M

AU - Mulder, Imke E

AU - Travis, Anthony J

AU - Lan, Annaig

AU - Cerf-Bensussan, Nadine

AU - Gaboriau-Routhiau, Valerie

AU - Garden, Karen

AU - Logan, Elizabeth

AU - Delday, Margaret I

AU - Coutts, Alistair G P

AU - Monnais, Edouard

AU - Ferraria, Vanessa C

AU - Inoue, Ryo

AU - Grant, George

AU - Aminov, Rustam I

N1 - Acknowledgments The authors would like to thank Andrew Gewirtz (Georgia State University, Atlanta, GA, USA) and Adam Cunningham (University of Birmingham, Edgbaston, Birmingham, UK) for generously providing the germ-free and conventional TLR5KO mice, respectively. The authors also wish to acknowledge a significant contribution to the inception of the work, experimental work, interpretation of results, and writing of the manuscript by Denise Kelly, as well as the support from RESAS (Rural and Environmental Science and Analytical Services) of the Scottish Government. EM and VF were supported by the Marie Curie Initial training network Fellowships funded by the EU (grant #215532). The authors acknowledge a generous support of Prof. Harry Flint and Dr. Sylvia Duncan in the microbiological part of this work. The skilled technical support of Gillian Campbell and Pauline Young at RINH Genomics is also gratefully acknowledged.

PY - 2017/9/26

Y1 - 2017/9/26

N2 - OBJECTIVE: Roseburia hominis is a flagellated gut anaerobic bacterium belonging to the Lachnospiraceae family within the Firmicutes phylum. A significant decrease of R. hominis colonization in the gut of ulcerative colitis patients has recently been demonstrated. In this work, we have investigated the mechanisms of R. hominis-host cross talk using both murine and in vitro models.DESIGN: The complete genome sequence of R. hominis A2-183 was determined. C3H/HeN germ-free mice were mono-colonized with R. hominis, and the host-microbe interaction was studied using histology, transcriptome analyses and FACS. Further investigations were performed in vitro and using the TLR5KO and DSS-colitis murine models.RESULTS: In the bacterium, R. hominis, host gut colonization upregulated genes involved in conjugation/mobilization, metabolism, motility, and chemotaxis. In the host cells, bacterial colonization upregulated genes related to antimicrobial peptides, gut barrier function, toll-like receptors (TLR) signaling, and T cell biology. CD4(+)CD25(+)FoxP3(+) T cell numbers increased in the lamina propria of both mono-associated and conventional mice treated with R. hominis. Treatment with the R. hominis bacterium provided protection against DSS-induced colitis. The role of flagellin in host-bacterium interaction was also investigated.CONCLUSION: Mono-association of mice with R. hominis bacteria results in specific bidirectional gene expression patterns. A set of genes thought to be important for host colonization are induced in R. hominis, while the host cells respond by strengthening gut barrier function and enhancing Treg population expansion, possibly via TLR5-flagellin signaling. Our data reveal the immunomodulatory properties of R. hominis that could be useful for the control and treatment of gut inflammation.

AB - OBJECTIVE: Roseburia hominis is a flagellated gut anaerobic bacterium belonging to the Lachnospiraceae family within the Firmicutes phylum. A significant decrease of R. hominis colonization in the gut of ulcerative colitis patients has recently been demonstrated. In this work, we have investigated the mechanisms of R. hominis-host cross talk using both murine and in vitro models.DESIGN: The complete genome sequence of R. hominis A2-183 was determined. C3H/HeN germ-free mice were mono-colonized with R. hominis, and the host-microbe interaction was studied using histology, transcriptome analyses and FACS. Further investigations were performed in vitro and using the TLR5KO and DSS-colitis murine models.RESULTS: In the bacterium, R. hominis, host gut colonization upregulated genes involved in conjugation/mobilization, metabolism, motility, and chemotaxis. In the host cells, bacterial colonization upregulated genes related to antimicrobial peptides, gut barrier function, toll-like receptors (TLR) signaling, and T cell biology. CD4(+)CD25(+)FoxP3(+) T cell numbers increased in the lamina propria of both mono-associated and conventional mice treated with R. hominis. Treatment with the R. hominis bacterium provided protection against DSS-induced colitis. The role of flagellin in host-bacterium interaction was also investigated.CONCLUSION: Mono-association of mice with R. hominis bacteria results in specific bidirectional gene expression patterns. A set of genes thought to be important for host colonization are induced in R. hominis, while the host cells respond by strengthening gut barrier function and enhancing Treg population expansion, possibly via TLR5-flagellin signaling. Our data reveal the immunomodulatory properties of R. hominis that could be useful for the control and treatment of gut inflammation.

KW - Journal Article

KW - Roseburia

KW - T lymphocytes

KW - immune tolerance

KW - inflammatory bowel disease

KW - flagellin

KW - TLR5

U2 - 10.3389/fimmu.2017.01166

DO - 10.3389/fimmu.2017.01166

M3 - Article

C2 - 29018440

SN - 1664-3224

VL - 8

SP - 1

EP - 14

JO - Frontiers in Immunology

JF - Frontiers in Immunology

M1 - 1166

ER -

Human Gut Symbiont Roseburia hominis Promotes and Regulates Innate Immunity

Abstract

Bibliographical note

Keywords

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GSE25544 Host/microbial cross-talk in the gut : in-depth investigation of the symbiotic effects of Roseburia hominis

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