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 languageEnglish
Article number1166
Pages (from-to)1-14
Number of pages14
JournalFrontiers in Immunology
Volume8
DOIs
Publication statusPublished - 26 Sep 2017

Fingerprint

Innate Immunity
Bacteria
Flagellin
Colitis
Genes
T-Lymphocytes
Anaerobic Bacteria
Toll-Like Receptors
Gene Expression Profiling
Chemotaxis
Ulcerative Colitis
varespladib methyl
Cell Biology
Histology
Mucous Membrane
Cell Count
Genome
Inflammation
Gene Expression
Peptides

Keywords

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

Cite this

Patterson, A. M., Mulder, I. E., Travis, A. J., Lan, A., Cerf-Bensussan, N., Gaboriau-Routhiau, V., ... Aminov, R. I. (2017). Human Gut Symbiont Roseburia hominis Promotes and Regulates Innate Immunity. Frontiers in Immunology, 8, 1-14. [1166]. https://doi.org/10.3389/fimmu.2017.01166

Human Gut Symbiont Roseburia hominis Promotes and Regulates Innate Immunity. / Patterson, Angela M; Mulder, Imke E; Travis, Anthony J; Lan, Annaig; Cerf-Bensussan, Nadine; Gaboriau-Routhiau, Valerie; Garden, Karen; Logan, Elizabeth; Delday, Margaret I; Coutts, Alistair G P; Monnais, Edouard; Ferraria, Vanessa C; Inoue, Ryo; Grant, George; Aminov, Rustam I.

In: Frontiers in Immunology, Vol. 8, 1166, 26.09.2017, p. 1-14.

Research output: Contribution to journalArticle

Patterson, AM, Mulder, IE, Travis, AJ, Lan, A, Cerf-Bensussan, N, Gaboriau-Routhiau, V, Garden, K, Logan, E, Delday, MI, Coutts, AGP, Monnais, E, Ferraria, VC, Inoue, R, Grant, G & Aminov, RI 2017, 'Human Gut Symbiont Roseburia hominis Promotes and Regulates Innate Immunity', Frontiers in Immunology, vol. 8, 1166, pp. 1-14. https://doi.org/10.3389/fimmu.2017.01166
Patterson AM, Mulder IE, Travis AJ, Lan A, Cerf-Bensussan N, Gaboriau-Routhiau V et al. Human Gut Symbiont Roseburia hominis Promotes and Regulates Innate Immunity. Frontiers in Immunology. 2017 Sep 26;8:1-14. 1166. https://doi.org/10.3389/fimmu.2017.01166
Patterson, Angela M ; Mulder, Imke E ; Travis, Anthony J ; Lan, Annaig ; Cerf-Bensussan, Nadine ; Gaboriau-Routhiau, Valerie ; Garden, Karen ; Logan, Elizabeth ; Delday, Margaret I ; Coutts, Alistair G P ; Monnais, Edouard ; Ferraria, Vanessa C ; Inoue, Ryo ; Grant, George ; Aminov, Rustam I. / Human Gut Symbiont Roseburia hominis Promotes and Regulates Innate Immunity. In: Frontiers in Immunology. 2017 ; Vol. 8. pp. 1-14.
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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.",
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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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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

VL - 8

SP - 1

EP - 14

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

M1 - 1166

ER -