Antibiotic-related gut dysbiosis induces lung immunodepression and worsens lung infection in mice
Background Gut dysbiosis due to the adverse effects of antibiotics affects outcomes of lung infection. Previous murine models relied on significant depletion of both gut and lung microbiota, rendering the analysis of immune gut-lung cross-talk difficult. Here, we study the effects of antibiotic-indu...
Ausführliche Beschreibung
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| Autor*in: |
Dessein, Rodrigue [verfasserIn] Bauduin, Marvin [verfasserIn] Grandjean, Teddy [verfasserIn] Le Guern, Rémi [verfasserIn] Figeac, Martin [verfasserIn] Beury, Delphine [verfasserIn] Faure, Karine [verfasserIn] Faveeuw, Christelle [verfasserIn] Guery, Benoit [verfasserIn] Gosset, Philippe [verfasserIn] Kipnis, Eric [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2020 |
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| Übergeordnetes Werk: |
Enthalten in: Critical care - London : BioMed Central, 1997, 24(2020), 1 vom: 15. Okt. |
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| Übergeordnetes Werk: |
volume:24 ; year:2020 ; number:1 ; day:15 ; month:10 |
| Links: |
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| DOI / URN: |
10.1186/s13054-020-03320-8 |
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| Katalog-ID: |
SPR041431626 |
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| 520 | |a Background Gut dysbiosis due to the adverse effects of antibiotics affects outcomes of lung infection. Previous murine models relied on significant depletion of both gut and lung microbiota, rendering the analysis of immune gut-lung cross-talk difficult. Here, we study the effects of antibiotic-induced gut dysbiosis without lung dysbiosis on lung immunity and the consequences on acute P. aeruginosa lung infection. Methods C57BL6 mice received 7 days oral vancomycin-colistin, followed by normal regimen or fecal microbial transplant or Fms-related tyrosine kinase 3 ligand (Flt3-Ligand) over 2 days, and then intra-nasal P. aeruginosa strain PAO1. Gut and lung microbiota were studied by next-generation sequencing, and lung infection outcomes were studied at 24 h. Effects of vancomycin-colistin on underlying immunity and bone marrow progenitors were studied in uninfected mice by flow cytometry in the lung, spleen, and bone marrow. Results Vancomycin-colistin administration induces widespread cellular immunosuppression in both the lung and spleen, decreases circulating hematopoietic cytokine Flt3-Ligand, and depresses dendritic cell bone marrow progenitors leading to worsening of P. aeruginosa lung infection outcomes (bacterial loads, lung injury, and survival). Reversal of these effects by fecal microbial transplant shows that these alterations are related to gut dysbiosis. Recombinant Flt3-Ligand reverses the effects of antibiotics on subsequent lung infection. Conclusions These results show that gut dysbiosis strongly impairs monocyte/dendritic progenitors and lung immunity, worsening outcomes of P. aeruginosa lung infection. Treatment with a fecal microbial transplant or immune stimulation by Flt3-Ligand both restore lung cellular responses to and outcomes of P. aeruginosa following antibiotic-induced gut dysbiosis. | ||
| 650 | 4 | |a Antibiotics |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Dysbiosis |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Murine model |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Flt3-ligand |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Fecal microbial transplant |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Bauduin, Marvin |e verfasserin |4 aut | |
| 700 | 1 | |a Grandjean, Teddy |e verfasserin |4 aut | |
| 700 | 1 | |a Le Guern, Rémi |e verfasserin |4 aut | |
| 700 | 1 | |a Figeac, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Beury, Delphine |e verfasserin |4 aut | |
| 700 | 1 | |a Faure, Karine |e verfasserin |4 aut | |
| 700 | 1 | |a Faveeuw, Christelle |e verfasserin |4 aut | |
| 700 | 1 | |a Guery, Benoit |e verfasserin |4 aut | |
| 700 | 1 | |a Gosset, Philippe |e verfasserin |4 aut | |
| 700 | 1 | |a Kipnis, Eric |e verfasserin |4 aut | |
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10.1186/s13054-020-03320-8 doi (DE-627)SPR041431626 (SPR)s13054-020-03320-8-e DE-627 ger DE-627 rakwb eng 610 ASE 44.00 bkl Dessein, Rodrigue verfasserin aut Antibiotic-related gut dysbiosis induces lung immunodepression and worsens lung infection in mice 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Gut dysbiosis due to the adverse effects of antibiotics affects outcomes of lung infection. Previous murine models relied on significant depletion of both gut and lung microbiota, rendering the analysis of immune gut-lung cross-talk difficult. Here, we study the effects of antibiotic-induced gut dysbiosis without lung dysbiosis on lung immunity and the consequences on acute P. aeruginosa lung infection. Methods C57BL6 mice received 7 days oral vancomycin-colistin, followed by normal regimen or fecal microbial transplant or Fms-related tyrosine kinase 3 ligand (Flt3-Ligand) over 2 days, and then intra-nasal P. aeruginosa strain PAO1. Gut and lung microbiota were studied by next-generation sequencing, and lung infection outcomes were studied at 24 h. Effects of vancomycin-colistin on underlying immunity and bone marrow progenitors were studied in uninfected mice by flow cytometry in the lung, spleen, and bone marrow. Results Vancomycin-colistin administration induces widespread cellular immunosuppression in both the lung and spleen, decreases circulating hematopoietic cytokine Flt3-Ligand, and depresses dendritic cell bone marrow progenitors leading to worsening of P. aeruginosa lung infection outcomes (bacterial loads, lung injury, and survival). Reversal of these effects by fecal microbial transplant shows that these alterations are related to gut dysbiosis. Recombinant Flt3-Ligand reverses the effects of antibiotics on subsequent lung infection. Conclusions These results show that gut dysbiosis strongly impairs monocyte/dendritic progenitors and lung immunity, worsening outcomes of P. aeruginosa lung infection. Treatment with a fecal microbial transplant or immune stimulation by Flt3-Ligand both restore lung cellular responses to and outcomes of P. aeruginosa following antibiotic-induced gut dysbiosis. Antibiotics (dpeaa)DE-He213 Dysbiosis (dpeaa)DE-He213 Murine model (dpeaa)DE-He213 Flt3-ligand (dpeaa)DE-He213 Fecal microbial transplant (dpeaa)DE-He213 Bauduin, Marvin verfasserin aut Grandjean, Teddy verfasserin aut Le Guern, Rémi verfasserin aut Figeac, Martin verfasserin aut Beury, Delphine verfasserin aut Faure, Karine verfasserin aut Faveeuw, Christelle verfasserin aut Guery, Benoit verfasserin aut Gosset, Philippe verfasserin aut Kipnis, Eric verfasserin aut Enthalten in Critical care London : BioMed Central, 1997 24(2020), 1 vom: 15. Okt. (DE-627)331258269 (DE-600)2051256-9 1364-8535 nnns volume:24 year:2020 number:1 day:15 month:10 https://dx.doi.org/10.1186/s13054-020-03320-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 44.00 ASE AR 24 2020 1 15 10 |
| spelling |
10.1186/s13054-020-03320-8 doi (DE-627)SPR041431626 (SPR)s13054-020-03320-8-e DE-627 ger DE-627 rakwb eng 610 ASE 44.00 bkl Dessein, Rodrigue verfasserin aut Antibiotic-related gut dysbiosis induces lung immunodepression and worsens lung infection in mice 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Gut dysbiosis due to the adverse effects of antibiotics affects outcomes of lung infection. Previous murine models relied on significant depletion of both gut and lung microbiota, rendering the analysis of immune gut-lung cross-talk difficult. Here, we study the effects of antibiotic-induced gut dysbiosis without lung dysbiosis on lung immunity and the consequences on acute P. aeruginosa lung infection. Methods C57BL6 mice received 7 days oral vancomycin-colistin, followed by normal regimen or fecal microbial transplant or Fms-related tyrosine kinase 3 ligand (Flt3-Ligand) over 2 days, and then intra-nasal P. aeruginosa strain PAO1. Gut and lung microbiota were studied by next-generation sequencing, and lung infection outcomes were studied at 24 h. Effects of vancomycin-colistin on underlying immunity and bone marrow progenitors were studied in uninfected mice by flow cytometry in the lung, spleen, and bone marrow. Results Vancomycin-colistin administration induces widespread cellular immunosuppression in both the lung and spleen, decreases circulating hematopoietic cytokine Flt3-Ligand, and depresses dendritic cell bone marrow progenitors leading to worsening of P. aeruginosa lung infection outcomes (bacterial loads, lung injury, and survival). Reversal of these effects by fecal microbial transplant shows that these alterations are related to gut dysbiosis. Recombinant Flt3-Ligand reverses the effects of antibiotics on subsequent lung infection. Conclusions These results show that gut dysbiosis strongly impairs monocyte/dendritic progenitors and lung immunity, worsening outcomes of P. aeruginosa lung infection. Treatment with a fecal microbial transplant or immune stimulation by Flt3-Ligand both restore lung cellular responses to and outcomes of P. aeruginosa following antibiotic-induced gut dysbiosis. Antibiotics (dpeaa)DE-He213 Dysbiosis (dpeaa)DE-He213 Murine model (dpeaa)DE-He213 Flt3-ligand (dpeaa)DE-He213 Fecal microbial transplant (dpeaa)DE-He213 Bauduin, Marvin verfasserin aut Grandjean, Teddy verfasserin aut Le Guern, Rémi verfasserin aut Figeac, Martin verfasserin aut Beury, Delphine verfasserin aut Faure, Karine verfasserin aut Faveeuw, Christelle verfasserin aut Guery, Benoit verfasserin aut Gosset, Philippe verfasserin aut Kipnis, Eric verfasserin aut Enthalten in Critical care London : BioMed Central, 1997 24(2020), 1 vom: 15. Okt. (DE-627)331258269 (DE-600)2051256-9 1364-8535 nnns volume:24 year:2020 number:1 day:15 month:10 https://dx.doi.org/10.1186/s13054-020-03320-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 44.00 ASE AR 24 2020 1 15 10 |
| allfields_unstemmed |
10.1186/s13054-020-03320-8 doi (DE-627)SPR041431626 (SPR)s13054-020-03320-8-e DE-627 ger DE-627 rakwb eng 610 ASE 44.00 bkl Dessein, Rodrigue verfasserin aut Antibiotic-related gut dysbiosis induces lung immunodepression and worsens lung infection in mice 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Gut dysbiosis due to the adverse effects of antibiotics affects outcomes of lung infection. Previous murine models relied on significant depletion of both gut and lung microbiota, rendering the analysis of immune gut-lung cross-talk difficult. Here, we study the effects of antibiotic-induced gut dysbiosis without lung dysbiosis on lung immunity and the consequences on acute P. aeruginosa lung infection. Methods C57BL6 mice received 7 days oral vancomycin-colistin, followed by normal regimen or fecal microbial transplant or Fms-related tyrosine kinase 3 ligand (Flt3-Ligand) over 2 days, and then intra-nasal P. aeruginosa strain PAO1. Gut and lung microbiota were studied by next-generation sequencing, and lung infection outcomes were studied at 24 h. Effects of vancomycin-colistin on underlying immunity and bone marrow progenitors were studied in uninfected mice by flow cytometry in the lung, spleen, and bone marrow. Results Vancomycin-colistin administration induces widespread cellular immunosuppression in both the lung and spleen, decreases circulating hematopoietic cytokine Flt3-Ligand, and depresses dendritic cell bone marrow progenitors leading to worsening of P. aeruginosa lung infection outcomes (bacterial loads, lung injury, and survival). Reversal of these effects by fecal microbial transplant shows that these alterations are related to gut dysbiosis. Recombinant Flt3-Ligand reverses the effects of antibiotics on subsequent lung infection. Conclusions These results show that gut dysbiosis strongly impairs monocyte/dendritic progenitors and lung immunity, worsening outcomes of P. aeruginosa lung infection. Treatment with a fecal microbial transplant or immune stimulation by Flt3-Ligand both restore lung cellular responses to and outcomes of P. aeruginosa following antibiotic-induced gut dysbiosis. Antibiotics (dpeaa)DE-He213 Dysbiosis (dpeaa)DE-He213 Murine model (dpeaa)DE-He213 Flt3-ligand (dpeaa)DE-He213 Fecal microbial transplant (dpeaa)DE-He213 Bauduin, Marvin verfasserin aut Grandjean, Teddy verfasserin aut Le Guern, Rémi verfasserin aut Figeac, Martin verfasserin aut Beury, Delphine verfasserin aut Faure, Karine verfasserin aut Faveeuw, Christelle verfasserin aut Guery, Benoit verfasserin aut Gosset, Philippe verfasserin aut Kipnis, Eric verfasserin aut Enthalten in Critical care London : BioMed Central, 1997 24(2020), 1 vom: 15. Okt. (DE-627)331258269 (DE-600)2051256-9 1364-8535 nnns volume:24 year:2020 number:1 day:15 month:10 https://dx.doi.org/10.1186/s13054-020-03320-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 44.00 ASE AR 24 2020 1 15 10 |
| allfieldsGer |
10.1186/s13054-020-03320-8 doi (DE-627)SPR041431626 (SPR)s13054-020-03320-8-e DE-627 ger DE-627 rakwb eng 610 ASE 44.00 bkl Dessein, Rodrigue verfasserin aut Antibiotic-related gut dysbiosis induces lung immunodepression and worsens lung infection in mice 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Gut dysbiosis due to the adverse effects of antibiotics affects outcomes of lung infection. Previous murine models relied on significant depletion of both gut and lung microbiota, rendering the analysis of immune gut-lung cross-talk difficult. Here, we study the effects of antibiotic-induced gut dysbiosis without lung dysbiosis on lung immunity and the consequences on acute P. aeruginosa lung infection. Methods C57BL6 mice received 7 days oral vancomycin-colistin, followed by normal regimen or fecal microbial transplant or Fms-related tyrosine kinase 3 ligand (Flt3-Ligand) over 2 days, and then intra-nasal P. aeruginosa strain PAO1. Gut and lung microbiota were studied by next-generation sequencing, and lung infection outcomes were studied at 24 h. Effects of vancomycin-colistin on underlying immunity and bone marrow progenitors were studied in uninfected mice by flow cytometry in the lung, spleen, and bone marrow. Results Vancomycin-colistin administration induces widespread cellular immunosuppression in both the lung and spleen, decreases circulating hematopoietic cytokine Flt3-Ligand, and depresses dendritic cell bone marrow progenitors leading to worsening of P. aeruginosa lung infection outcomes (bacterial loads, lung injury, and survival). Reversal of these effects by fecal microbial transplant shows that these alterations are related to gut dysbiosis. Recombinant Flt3-Ligand reverses the effects of antibiotics on subsequent lung infection. Conclusions These results show that gut dysbiosis strongly impairs monocyte/dendritic progenitors and lung immunity, worsening outcomes of P. aeruginosa lung infection. Treatment with a fecal microbial transplant or immune stimulation by Flt3-Ligand both restore lung cellular responses to and outcomes of P. aeruginosa following antibiotic-induced gut dysbiosis. Antibiotics (dpeaa)DE-He213 Dysbiosis (dpeaa)DE-He213 Murine model (dpeaa)DE-He213 Flt3-ligand (dpeaa)DE-He213 Fecal microbial transplant (dpeaa)DE-He213 Bauduin, Marvin verfasserin aut Grandjean, Teddy verfasserin aut Le Guern, Rémi verfasserin aut Figeac, Martin verfasserin aut Beury, Delphine verfasserin aut Faure, Karine verfasserin aut Faveeuw, Christelle verfasserin aut Guery, Benoit verfasserin aut Gosset, Philippe verfasserin aut Kipnis, Eric verfasserin aut Enthalten in Critical care London : BioMed Central, 1997 24(2020), 1 vom: 15. Okt. (DE-627)331258269 (DE-600)2051256-9 1364-8535 nnns volume:24 year:2020 number:1 day:15 month:10 https://dx.doi.org/10.1186/s13054-020-03320-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 44.00 ASE AR 24 2020 1 15 10 |
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10.1186/s13054-020-03320-8 doi (DE-627)SPR041431626 (SPR)s13054-020-03320-8-e DE-627 ger DE-627 rakwb eng 610 ASE 44.00 bkl Dessein, Rodrigue verfasserin aut Antibiotic-related gut dysbiosis induces lung immunodepression and worsens lung infection in mice 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Gut dysbiosis due to the adverse effects of antibiotics affects outcomes of lung infection. Previous murine models relied on significant depletion of both gut and lung microbiota, rendering the analysis of immune gut-lung cross-talk difficult. Here, we study the effects of antibiotic-induced gut dysbiosis without lung dysbiosis on lung immunity and the consequences on acute P. aeruginosa lung infection. Methods C57BL6 mice received 7 days oral vancomycin-colistin, followed by normal regimen or fecal microbial transplant or Fms-related tyrosine kinase 3 ligand (Flt3-Ligand) over 2 days, and then intra-nasal P. aeruginosa strain PAO1. Gut and lung microbiota were studied by next-generation sequencing, and lung infection outcomes were studied at 24 h. Effects of vancomycin-colistin on underlying immunity and bone marrow progenitors were studied in uninfected mice by flow cytometry in the lung, spleen, and bone marrow. Results Vancomycin-colistin administration induces widespread cellular immunosuppression in both the lung and spleen, decreases circulating hematopoietic cytokine Flt3-Ligand, and depresses dendritic cell bone marrow progenitors leading to worsening of P. aeruginosa lung infection outcomes (bacterial loads, lung injury, and survival). Reversal of these effects by fecal microbial transplant shows that these alterations are related to gut dysbiosis. Recombinant Flt3-Ligand reverses the effects of antibiotics on subsequent lung infection. Conclusions These results show that gut dysbiosis strongly impairs monocyte/dendritic progenitors and lung immunity, worsening outcomes of P. aeruginosa lung infection. Treatment with a fecal microbial transplant or immune stimulation by Flt3-Ligand both restore lung cellular responses to and outcomes of P. aeruginosa following antibiotic-induced gut dysbiosis. Antibiotics (dpeaa)DE-He213 Dysbiosis (dpeaa)DE-He213 Murine model (dpeaa)DE-He213 Flt3-ligand (dpeaa)DE-He213 Fecal microbial transplant (dpeaa)DE-He213 Bauduin, Marvin verfasserin aut Grandjean, Teddy verfasserin aut Le Guern, Rémi verfasserin aut Figeac, Martin verfasserin aut Beury, Delphine verfasserin aut Faure, Karine verfasserin aut Faveeuw, Christelle verfasserin aut Guery, Benoit verfasserin aut Gosset, Philippe verfasserin aut Kipnis, Eric verfasserin aut Enthalten in Critical care London : BioMed Central, 1997 24(2020), 1 vom: 15. Okt. (DE-627)331258269 (DE-600)2051256-9 1364-8535 nnns volume:24 year:2020 number:1 day:15 month:10 https://dx.doi.org/10.1186/s13054-020-03320-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 44.00 ASE AR 24 2020 1 15 10 |
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Antibiotic-related gut dysbiosis induces lung immunodepression and worsens lung infection in mice |
| abstract |
Background Gut dysbiosis due to the adverse effects of antibiotics affects outcomes of lung infection. Previous murine models relied on significant depletion of both gut and lung microbiota, rendering the analysis of immune gut-lung cross-talk difficult. Here, we study the effects of antibiotic-induced gut dysbiosis without lung dysbiosis on lung immunity and the consequences on acute P. aeruginosa lung infection. Methods C57BL6 mice received 7 days oral vancomycin-colistin, followed by normal regimen or fecal microbial transplant or Fms-related tyrosine kinase 3 ligand (Flt3-Ligand) over 2 days, and then intra-nasal P. aeruginosa strain PAO1. Gut and lung microbiota were studied by next-generation sequencing, and lung infection outcomes were studied at 24 h. Effects of vancomycin-colistin on underlying immunity and bone marrow progenitors were studied in uninfected mice by flow cytometry in the lung, spleen, and bone marrow. Results Vancomycin-colistin administration induces widespread cellular immunosuppression in both the lung and spleen, decreases circulating hematopoietic cytokine Flt3-Ligand, and depresses dendritic cell bone marrow progenitors leading to worsening of P. aeruginosa lung infection outcomes (bacterial loads, lung injury, and survival). Reversal of these effects by fecal microbial transplant shows that these alterations are related to gut dysbiosis. Recombinant Flt3-Ligand reverses the effects of antibiotics on subsequent lung infection. Conclusions These results show that gut dysbiosis strongly impairs monocyte/dendritic progenitors and lung immunity, worsening outcomes of P. aeruginosa lung infection. Treatment with a fecal microbial transplant or immune stimulation by Flt3-Ligand both restore lung cellular responses to and outcomes of P. aeruginosa following antibiotic-induced gut dysbiosis. |
| abstractGer |
Background Gut dysbiosis due to the adverse effects of antibiotics affects outcomes of lung infection. Previous murine models relied on significant depletion of both gut and lung microbiota, rendering the analysis of immune gut-lung cross-talk difficult. Here, we study the effects of antibiotic-induced gut dysbiosis without lung dysbiosis on lung immunity and the consequences on acute P. aeruginosa lung infection. Methods C57BL6 mice received 7 days oral vancomycin-colistin, followed by normal regimen or fecal microbial transplant or Fms-related tyrosine kinase 3 ligand (Flt3-Ligand) over 2 days, and then intra-nasal P. aeruginosa strain PAO1. Gut and lung microbiota were studied by next-generation sequencing, and lung infection outcomes were studied at 24 h. Effects of vancomycin-colistin on underlying immunity and bone marrow progenitors were studied in uninfected mice by flow cytometry in the lung, spleen, and bone marrow. Results Vancomycin-colistin administration induces widespread cellular immunosuppression in both the lung and spleen, decreases circulating hematopoietic cytokine Flt3-Ligand, and depresses dendritic cell bone marrow progenitors leading to worsening of P. aeruginosa lung infection outcomes (bacterial loads, lung injury, and survival). Reversal of these effects by fecal microbial transplant shows that these alterations are related to gut dysbiosis. Recombinant Flt3-Ligand reverses the effects of antibiotics on subsequent lung infection. Conclusions These results show that gut dysbiosis strongly impairs monocyte/dendritic progenitors and lung immunity, worsening outcomes of P. aeruginosa lung infection. Treatment with a fecal microbial transplant or immune stimulation by Flt3-Ligand both restore lung cellular responses to and outcomes of P. aeruginosa following antibiotic-induced gut dysbiosis. |
| abstract_unstemmed |
Background Gut dysbiosis due to the adverse effects of antibiotics affects outcomes of lung infection. Previous murine models relied on significant depletion of both gut and lung microbiota, rendering the analysis of immune gut-lung cross-talk difficult. Here, we study the effects of antibiotic-induced gut dysbiosis without lung dysbiosis on lung immunity and the consequences on acute P. aeruginosa lung infection. Methods C57BL6 mice received 7 days oral vancomycin-colistin, followed by normal regimen or fecal microbial transplant or Fms-related tyrosine kinase 3 ligand (Flt3-Ligand) over 2 days, and then intra-nasal P. aeruginosa strain PAO1. Gut and lung microbiota were studied by next-generation sequencing, and lung infection outcomes were studied at 24 h. Effects of vancomycin-colistin on underlying immunity and bone marrow progenitors were studied in uninfected mice by flow cytometry in the lung, spleen, and bone marrow. Results Vancomycin-colistin administration induces widespread cellular immunosuppression in both the lung and spleen, decreases circulating hematopoietic cytokine Flt3-Ligand, and depresses dendritic cell bone marrow progenitors leading to worsening of P. aeruginosa lung infection outcomes (bacterial loads, lung injury, and survival). Reversal of these effects by fecal microbial transplant shows that these alterations are related to gut dysbiosis. Recombinant Flt3-Ligand reverses the effects of antibiotics on subsequent lung infection. Conclusions These results show that gut dysbiosis strongly impairs monocyte/dendritic progenitors and lung immunity, worsening outcomes of P. aeruginosa lung infection. Treatment with a fecal microbial transplant or immune stimulation by Flt3-Ligand both restore lung cellular responses to and outcomes of P. aeruginosa following antibiotic-induced gut dysbiosis. |
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| title_short |
Antibiotic-related gut dysbiosis induces lung immunodepression and worsens lung infection in mice |
| url |
https://dx.doi.org/10.1186/s13054-020-03320-8 |
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| author2 |
Bauduin, Marvin Grandjean, Teddy Le Guern, Rémi Figeac, Martin Beury, Delphine Faure, Karine Faveeuw, Christelle Guery, Benoit Gosset, Philippe Kipnis, Eric |
| author2Str |
Bauduin, Marvin Grandjean, Teddy Le Guern, Rémi Figeac, Martin Beury, Delphine Faure, Karine Faveeuw, Christelle Guery, Benoit Gosset, Philippe Kipnis, Eric |
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| doi_str |
10.1186/s13054-020-03320-8 |
| up_date |
2024-07-03T22:03:43.904Z |
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