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Jose G Santos - One of the best experts on this subject based on the ideXlab platform.
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concerted pyridinolysis of aryl 2 4 6 Trinitrophenyl carbonates
Journal of Organic Chemistry, 2009Co-Authors: Enrique A Castro, Mariela Ramos, Jose G SantosAbstract:The Bronsted plots for the title reactions are linear with slopes of 0.53−0.56. The magnitude of the slopes and the fact that there are no breaks at the predicted pKa for stepwise mechanisms indicate that these reactions are concerted. This finding is in great contrast to the stepwise mechanisms found for the pyridinolysis of other carbonates. The concerted mechanism is attributed to the fact that the title carbonates possess two O-aryl groups, one of them being an exceptionally good nucleofuge.
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kinetics and mechanism of the benzenethiolysis of o ethyl s 2 4 dinitrophenyl and o ethyl s 2 4 6 Trinitrophenyl dithiocarbonates and o methyl o 2 4 dinitrophenyl thiocarbonate
Journal of Organic Chemistry, 2003Co-Authors: Enrique A Castro, Paulina Pavez, Jose G SantosAbstract:Reactions of O-ethyl 2,4-dinitrophenyl dithiocarbonate (EDNPDTC), O-ethyl 2,4,6-Trinitrophenyl dithiocarbonate (ETNPDTC), and O-methyl O-(2,4-dinitrophenyl) thiocarbonate (MDNPTOC) with a series of benzenethiolate anions in aqueous solution, at 25.0 °C and an ionic strength of 0.2 M (KCl), are subjected to a kinetic investigation. Under excess benzenethiolate, these reactions obey pseudo-first-order kinetics and are first order in benzenethiolate. Nonetheless, similar reactant concentrations were used in the reactions of 4-nitrobenzenethiolate anion with the ethyl Trinitrophenyl ester (ETNPDTC), which showed overall second-order kinetics. The nucleophilic rate constants (kN) are pH independent, except those for the reactions of ETNPDTC with the X-benzenethiolates with X = H, 4-Cl, and 3-Cl, which increase as pH decreases. The Bronsted-type plots (log kN vs pKa of benzenethiols) are linear with slopes β = 0.66 for the reactions of both ethyl dinitrophenyl ester (EDNPDTC) and ethyl Trinitrophenyl ester (ETN...
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kinetics and mechanism of the benzenethiolysis of 2 4 dinitrophenyl and 2 4 6 Trinitrophenyl methyl carbonates and s 2 4 dinitrophenyl and s 2 4 6 Trinitrophenyl ethyl thiolcarbonates
Journal of Organic Chemistry, 2003Co-Authors: Enrique A Castro, Paulina Pavez, Jose G SantosAbstract:The reactions of 2,4-dinitrophenyl and 2,4,6-Trinitrophenyl methyl carbonates (DNPC and TNPC, respectively) and S-(2,4-dinitrophenyl) and S-(2,4,6-Trinitrophenyl) ethyl thiolcarbonates (DNPTC and TNPTC, respectively) with a series of benzenethiolate anions were subjected to a kinetic investigation in water, at 25.0 degrees C, and an ionic strength of 0.2 M (KCl). These reactions obey pseudo-first-order kinetics, under excess of benzenethiolate, and are first order in the latter reactant. However, comparable reactant concentrations were used in the reactions of 4-nitrobenzenethiolate anion with TNPC and TNPTC, which showed second-order kinetics. The nucleophilic rate constants are pH independent, except those for the reactions of TNPC with 4-methoxy- and pentafluorobenzenethiolates, and TNPTC with benzenethiolate and 4-chloro- and 3-chlorobenzenethiolates, which show acid dependence. The Bronsted-type plots for the nucleophilic rate constants are linear with slopes beta = 0.9, 1.0, 0.9, and 0.9 for the reactions of DNPC, TNPC, DNPTC, and TNPTC, respectively. No break in the Bronsted plot was found for the reactions of DNPC and DNPTC at pK(a) ca. 4.1 and 3.4, respectively, consistent with concerted mechanisms. TNPC is more reactive toward benzenethiolate anions than DNPC, and TNPTC more than DNPTC due to the better leaving groups involved. Comparison of the kinetic results obtained in this work with those for the concerted phenolysis of the same substrates shows that benzenethiolate anions are better nucleophiles toward carbonates than isobasic phenoxide anions. This is explained by Pearson's "hard and soft acids and bases" principle.
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concerted mechanisms of the reactions of 2 4 6 Trinitrophenyl methyl carbonate and 2 4 6 Trinitrophenyl acetate with secondary alicyclic amines
Journal of Organic Chemistry, 2001Co-Authors: Enrique A Castro, Maria Cubillos, Jose G SantosAbstract:The reactions of secondary alicyclic amines with 2,4,6-Trinitrophenyl methyl carbonate (TNPMC) and 2,4,6-Trinitrophenyl acetate (TNPA) are subjected to a kinetic study in aqueous solution, 25.0 degrees C, ionic strength 0.2 (KCl). The reactions are studied by following spectrophotometrically (360 nm) the release of the 2,4,6-trinitrophenoxide anion. Under amine excess, pseudo-first-order rate coefficients (k(obsd)) are found. Plots of k(obsd) vs [amine] are linear, with the slope (kN) independent of pH. The Bronsted-type plots (log k(N) vs pK(a) of the conjugate acid of the amines) are linear, with slopes beta = 0.41 and beta = 0.36 for the reactions of TNPA and TNPMC, respectively. The predicted breaks of the Bronsted plots for stepwise mechanisms are pK(a)0 = 6.8 and 7.3, respectively. The lack of Bronsted breaks for these reactions and the values of the Bronsted slopes are consistent with concerted mechanisms. By comparison of the reactions under investigation among them and with similar aminolysis and pyridinolysis, the following conclusions can be drawn: (i) Secondary alicyclic amines react with TNPA and TNPMC by concerted mechanisms. (ii) TNPA is more reactive toward these amines than TNPMC due to the greater electron release of MeO from the latter substrate. (iii) The change of 2,4-dinitrophenoxy to 2,4,6-trinitrophenoxy in the zwitterionic tetrahedral intermediate (T+/-) formed in the reactions of the title amines with 2,4-dinitrophenyl acetate greatly destabilizes T+/-. (iv) Secondary alicyclic amines destabilize T+/- relative to pyridines. (v) The intermediate T+/- formed in the reactions of the title amines with S-(2,4,6-Trinitrophenyl) acetate is greatly destabilized by substitution of S-(2,4,6-Trinitrophenyl) by O-(2,4,6-Trinitrophenyl) as the leaving group.
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kinetics and mechanism of the pyridinolysis of 2 4 6 Trinitrophenyl acetate and 2 4 6 Trinitrophenyl methyl carbonate
Journal of Organic Chemistry, 1992Co-Authors: Enrique A Castro, Fernando Ibanez, Silvia Lagos, Marlene Schick, Jose G SantosAbstract:The title reactions are subject to a kinetic study in aqueous solution at 25.0 o C, ionic strength 0.2 M. The reactions are frst order in both the substrate and the free base pyridine. The Bronsted-type plots obtained are nonlinear with slopes β 1 =0.2 and β 2 =0.8 at high and low basicities of the pyridines, respectively, for both sustrates. The pK a values at the Bronsted breaks (pK a o ) are 5.0 and 6.5 for the acetate (TNPA) and the carbonate (TNPMC), respectively
Enrique A Castro - One of the best experts on this subject based on the ideXlab platform.
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concerted pyridinolysis of aryl 2 4 6 Trinitrophenyl carbonates
Journal of Organic Chemistry, 2009Co-Authors: Enrique A Castro, Mariela Ramos, Jose G SantosAbstract:The Bronsted plots for the title reactions are linear with slopes of 0.53−0.56. The magnitude of the slopes and the fact that there are no breaks at the predicted pKa for stepwise mechanisms indicate that these reactions are concerted. This finding is in great contrast to the stepwise mechanisms found for the pyridinolysis of other carbonates. The concerted mechanism is attributed to the fact that the title carbonates possess two O-aryl groups, one of them being an exceptionally good nucleofuge.
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kinetics and mechanism of the benzenethiolysis of o ethyl s 2 4 dinitrophenyl and o ethyl s 2 4 6 Trinitrophenyl dithiocarbonates and o methyl o 2 4 dinitrophenyl thiocarbonate
Journal of Organic Chemistry, 2003Co-Authors: Enrique A Castro, Paulina Pavez, Jose G SantosAbstract:Reactions of O-ethyl 2,4-dinitrophenyl dithiocarbonate (EDNPDTC), O-ethyl 2,4,6-Trinitrophenyl dithiocarbonate (ETNPDTC), and O-methyl O-(2,4-dinitrophenyl) thiocarbonate (MDNPTOC) with a series of benzenethiolate anions in aqueous solution, at 25.0 °C and an ionic strength of 0.2 M (KCl), are subjected to a kinetic investigation. Under excess benzenethiolate, these reactions obey pseudo-first-order kinetics and are first order in benzenethiolate. Nonetheless, similar reactant concentrations were used in the reactions of 4-nitrobenzenethiolate anion with the ethyl Trinitrophenyl ester (ETNPDTC), which showed overall second-order kinetics. The nucleophilic rate constants (kN) are pH independent, except those for the reactions of ETNPDTC with the X-benzenethiolates with X = H, 4-Cl, and 3-Cl, which increase as pH decreases. The Bronsted-type plots (log kN vs pKa of benzenethiols) are linear with slopes β = 0.66 for the reactions of both ethyl dinitrophenyl ester (EDNPDTC) and ethyl Trinitrophenyl ester (ETN...
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kinetics and mechanism of the benzenethiolysis of 2 4 dinitrophenyl and 2 4 6 Trinitrophenyl methyl carbonates and s 2 4 dinitrophenyl and s 2 4 6 Trinitrophenyl ethyl thiolcarbonates
Journal of Organic Chemistry, 2003Co-Authors: Enrique A Castro, Paulina Pavez, Jose G SantosAbstract:The reactions of 2,4-dinitrophenyl and 2,4,6-Trinitrophenyl methyl carbonates (DNPC and TNPC, respectively) and S-(2,4-dinitrophenyl) and S-(2,4,6-Trinitrophenyl) ethyl thiolcarbonates (DNPTC and TNPTC, respectively) with a series of benzenethiolate anions were subjected to a kinetic investigation in water, at 25.0 degrees C, and an ionic strength of 0.2 M (KCl). These reactions obey pseudo-first-order kinetics, under excess of benzenethiolate, and are first order in the latter reactant. However, comparable reactant concentrations were used in the reactions of 4-nitrobenzenethiolate anion with TNPC and TNPTC, which showed second-order kinetics. The nucleophilic rate constants are pH independent, except those for the reactions of TNPC with 4-methoxy- and pentafluorobenzenethiolates, and TNPTC with benzenethiolate and 4-chloro- and 3-chlorobenzenethiolates, which show acid dependence. The Bronsted-type plots for the nucleophilic rate constants are linear with slopes beta = 0.9, 1.0, 0.9, and 0.9 for the reactions of DNPC, TNPC, DNPTC, and TNPTC, respectively. No break in the Bronsted plot was found for the reactions of DNPC and DNPTC at pK(a) ca. 4.1 and 3.4, respectively, consistent with concerted mechanisms. TNPC is more reactive toward benzenethiolate anions than DNPC, and TNPTC more than DNPTC due to the better leaving groups involved. Comparison of the kinetic results obtained in this work with those for the concerted phenolysis of the same substrates shows that benzenethiolate anions are better nucleophiles toward carbonates than isobasic phenoxide anions. This is explained by Pearson's "hard and soft acids and bases" principle.
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concerted mechanisms of the reactions of 2 4 6 Trinitrophenyl methyl carbonate and 2 4 6 Trinitrophenyl acetate with secondary alicyclic amines
Journal of Organic Chemistry, 2001Co-Authors: Enrique A Castro, Maria Cubillos, Jose G SantosAbstract:The reactions of secondary alicyclic amines with 2,4,6-Trinitrophenyl methyl carbonate (TNPMC) and 2,4,6-Trinitrophenyl acetate (TNPA) are subjected to a kinetic study in aqueous solution, 25.0 degrees C, ionic strength 0.2 (KCl). The reactions are studied by following spectrophotometrically (360 nm) the release of the 2,4,6-trinitrophenoxide anion. Under amine excess, pseudo-first-order rate coefficients (k(obsd)) are found. Plots of k(obsd) vs [amine] are linear, with the slope (kN) independent of pH. The Bronsted-type plots (log k(N) vs pK(a) of the conjugate acid of the amines) are linear, with slopes beta = 0.41 and beta = 0.36 for the reactions of TNPA and TNPMC, respectively. The predicted breaks of the Bronsted plots for stepwise mechanisms are pK(a)0 = 6.8 and 7.3, respectively. The lack of Bronsted breaks for these reactions and the values of the Bronsted slopes are consistent with concerted mechanisms. By comparison of the reactions under investigation among them and with similar aminolysis and pyridinolysis, the following conclusions can be drawn: (i) Secondary alicyclic amines react with TNPA and TNPMC by concerted mechanisms. (ii) TNPA is more reactive toward these amines than TNPMC due to the greater electron release of MeO from the latter substrate. (iii) The change of 2,4-dinitrophenoxy to 2,4,6-trinitrophenoxy in the zwitterionic tetrahedral intermediate (T+/-) formed in the reactions of the title amines with 2,4-dinitrophenyl acetate greatly destabilizes T+/-. (iv) Secondary alicyclic amines destabilize T+/- relative to pyridines. (v) The intermediate T+/- formed in the reactions of the title amines with S-(2,4,6-Trinitrophenyl) acetate is greatly destabilized by substitution of S-(2,4,6-Trinitrophenyl) by O-(2,4,6-Trinitrophenyl) as the leaving group.
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kinetics and mechanism of the pyridinolysis of 2 4 6 Trinitrophenyl acetate and 2 4 6 Trinitrophenyl methyl carbonate
Journal of Organic Chemistry, 1992Co-Authors: Enrique A Castro, Fernando Ibanez, Silvia Lagos, Marlene Schick, Jose G SantosAbstract:The title reactions are subject to a kinetic study in aqueous solution at 25.0 o C, ionic strength 0.2 M. The reactions are frst order in both the substrate and the free base pyridine. The Bronsted-type plots obtained are nonlinear with slopes β 1 =0.2 and β 2 =0.8 at high and low basicities of the pyridines, respectively, for both sustrates. The pK a values at the Bronsted breaks (pK a o ) are 5.0 and 6.5 for the acetate (TNPA) and the carbonate (TNPMC), respectively
Marian Szczepanik - One of the best experts on this subject based on the ideXlab platform.
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broad spectrum antibiotic enrofloxacin modulates contact sensitivity through gut microbiota in a murine model
The Journal of Allergy and Clinical Immunology, 2017Co-Authors: Anna Strzepa, Monika Majewskaszczepanik, Francis M Lobo, Marian SzczepanikAbstract:Background Medical advances in the field of infection therapy have led to an increasing use of antibiotics, which, apart from eliminating pathogens, also partially eliminate naturally existing commensal bacteria. It has become increasingly clear that less exposure to microbiota early in life may contribute to the observed rise in "immune-mediated" diseases, including autoimmunity and allergy. Objective We sought to test whether the change of gut microbiota with the broad spectrum antibiotic enrofloxacin will modulate contact sensitivity (CS) in mice. Methods Natural gut microbiota were modified by oral treatment with enrofloxacin prior to sensitization with Trinitrophenyl chloride followed by CS testing. Finally, adoptive cell transfers were performed to characterize the regulatory cells that are induced by microbiota modification. Results Oral treatment with enrofloxacin suppresses CS and production of anti–Trinitrophenyl chloride IgG1 antibodies. Adoptive transfer experiments show that antibiotic administration favors induction of regulatory cells that suppress CS. Flow cytometry and adoptive transfer of purified cells show that antibiotic-induced suppression of CS is mediated by TCR αβ + CD4 + CD25 + FoxP3 + Treg, CD19 + B220 + CD5 + IL-10 + , IL-10 + Tr1, and IL-10 + TCR γδ + cells. Treatment with the antibiotic induces dysbiosis characterized by increased proportion of Clostridium coccoides (cluster XIVa), C coccoides – Eubacterium rectale (cluster XIVab), Bacteroidetes, and Bifidobacterium spp, but decreased segmented filamentous bacteria. Transfer of antibiotic-modified gut microbiota inhibits CS, but this response can be restored through oral transfer of control gut bacteria to antibiotic-treated animals. Conclusions Oral treatment with a broad spectrum antibiotic modifies gut microbiota composition and promotes anti-inflammatory response, suggesting that manipulation of gut microbiota can be a powerful tool to modulate the course of CS.
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broad spectrum antibiotic enrofloxacin modulates contact sensitivity through gut microbiota in a murine model
The Journal of Allergy and Clinical Immunology, 2017Co-Authors: Anna Strzepa, Monika Majewskaszczepanik, Francis M Lobo, Li Wen, Marian SzczepanikAbstract:Background Medical advances in the field of infection therapy have led to an increasing use of antibiotics, which, apart from eliminating pathogens, also partially eliminate naturally existing commensal bacteria. It has become increasingly clear that less exposure to microbiota early in life may contribute to the observed rise in "immune-mediated" diseases, including autoimmunity and allergy. Objective We sought to test whether the change of gut microbiota with the broad spectrum antibiotic enrofloxacin will modulate contact sensitivity (CS) in mice. Methods Natural gut microbiota were modified by oral treatment with enrofloxacin prior to sensitization with Trinitrophenyl chloride followed by CS testing. Finally, adoptive cell transfers were performed to characterize the regulatory cells that are induced by microbiota modification. Results Oral treatment with enrofloxacin suppresses CS and production of anti–Trinitrophenyl chloride IgG1 antibodies. Adoptive transfer experiments show that antibiotic administration favors induction of regulatory cells that suppress CS. Flow cytometry and adoptive transfer of purified cells show that antibiotic-induced suppression of CS is mediated by TCR αβ + CD4 + CD25 + FoxP3 + Treg, CD19 + B220 + CD5 + IL-10 + , IL-10 + Tr1, and IL-10 + TCR γδ + cells. Treatment with the antibiotic induces dysbiosis characterized by increased proportion of Clostridium coccoides (cluster XIVa), C coccoides – Eubacterium rectale (cluster XIVab), Bacteroidetes, and Bifidobacterium spp, but decreased segmented filamentous bacteria. Transfer of antibiotic-modified gut microbiota inhibits CS, but this response can be restored through oral transfer of control gut bacteria to antibiotic-treated animals. Conclusions Oral treatment with a broad spectrum antibiotic modifies gut microbiota composition and promotes anti-inflammatory response, suggesting that manipulation of gut microbiota can be a powerful tool to modulate the course of CS.
Anna Strzepa - One of the best experts on this subject based on the ideXlab platform.
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broad spectrum antibiotic enrofloxacin modulates contact sensitivity through gut microbiota in a murine model
The Journal of Allergy and Clinical Immunology, 2017Co-Authors: Anna Strzepa, Monika Majewskaszczepanik, Francis M Lobo, Marian SzczepanikAbstract:Background Medical advances in the field of infection therapy have led to an increasing use of antibiotics, which, apart from eliminating pathogens, also partially eliminate naturally existing commensal bacteria. It has become increasingly clear that less exposure to microbiota early in life may contribute to the observed rise in "immune-mediated" diseases, including autoimmunity and allergy. Objective We sought to test whether the change of gut microbiota with the broad spectrum antibiotic enrofloxacin will modulate contact sensitivity (CS) in mice. Methods Natural gut microbiota were modified by oral treatment with enrofloxacin prior to sensitization with Trinitrophenyl chloride followed by CS testing. Finally, adoptive cell transfers were performed to characterize the regulatory cells that are induced by microbiota modification. Results Oral treatment with enrofloxacin suppresses CS and production of anti–Trinitrophenyl chloride IgG1 antibodies. Adoptive transfer experiments show that antibiotic administration favors induction of regulatory cells that suppress CS. Flow cytometry and adoptive transfer of purified cells show that antibiotic-induced suppression of CS is mediated by TCR αβ + CD4 + CD25 + FoxP3 + Treg, CD19 + B220 + CD5 + IL-10 + , IL-10 + Tr1, and IL-10 + TCR γδ + cells. Treatment with the antibiotic induces dysbiosis characterized by increased proportion of Clostridium coccoides (cluster XIVa), C coccoides – Eubacterium rectale (cluster XIVab), Bacteroidetes, and Bifidobacterium spp, but decreased segmented filamentous bacteria. Transfer of antibiotic-modified gut microbiota inhibits CS, but this response can be restored through oral transfer of control gut bacteria to antibiotic-treated animals. Conclusions Oral treatment with a broad spectrum antibiotic modifies gut microbiota composition and promotes anti-inflammatory response, suggesting that manipulation of gut microbiota can be a powerful tool to modulate the course of CS.
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broad spectrum antibiotic enrofloxacin modulates contact sensitivity through gut microbiota in a murine model
The Journal of Allergy and Clinical Immunology, 2017Co-Authors: Anna Strzepa, Monika Majewskaszczepanik, Francis M Lobo, Li Wen, Marian SzczepanikAbstract:Background Medical advances in the field of infection therapy have led to an increasing use of antibiotics, which, apart from eliminating pathogens, also partially eliminate naturally existing commensal bacteria. It has become increasingly clear that less exposure to microbiota early in life may contribute to the observed rise in "immune-mediated" diseases, including autoimmunity and allergy. Objective We sought to test whether the change of gut microbiota with the broad spectrum antibiotic enrofloxacin will modulate contact sensitivity (CS) in mice. Methods Natural gut microbiota were modified by oral treatment with enrofloxacin prior to sensitization with Trinitrophenyl chloride followed by CS testing. Finally, adoptive cell transfers were performed to characterize the regulatory cells that are induced by microbiota modification. Results Oral treatment with enrofloxacin suppresses CS and production of anti–Trinitrophenyl chloride IgG1 antibodies. Adoptive transfer experiments show that antibiotic administration favors induction of regulatory cells that suppress CS. Flow cytometry and adoptive transfer of purified cells show that antibiotic-induced suppression of CS is mediated by TCR αβ + CD4 + CD25 + FoxP3 + Treg, CD19 + B220 + CD5 + IL-10 + , IL-10 + Tr1, and IL-10 + TCR γδ + cells. Treatment with the antibiotic induces dysbiosis characterized by increased proportion of Clostridium coccoides (cluster XIVa), C coccoides – Eubacterium rectale (cluster XIVab), Bacteroidetes, and Bifidobacterium spp, but decreased segmented filamentous bacteria. Transfer of antibiotic-modified gut microbiota inhibits CS, but this response can be restored through oral transfer of control gut bacteria to antibiotic-treated animals. Conclusions Oral treatment with a broad spectrum antibiotic modifies gut microbiota composition and promotes anti-inflammatory response, suggesting that manipulation of gut microbiota can be a powerful tool to modulate the course of CS.
Monika Majewskaszczepanik - One of the best experts on this subject based on the ideXlab platform.
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broad spectrum antibiotic enrofloxacin modulates contact sensitivity through gut microbiota in a murine model
The Journal of Allergy and Clinical Immunology, 2017Co-Authors: Anna Strzepa, Monika Majewskaszczepanik, Francis M Lobo, Marian SzczepanikAbstract:Background Medical advances in the field of infection therapy have led to an increasing use of antibiotics, which, apart from eliminating pathogens, also partially eliminate naturally existing commensal bacteria. It has become increasingly clear that less exposure to microbiota early in life may contribute to the observed rise in "immune-mediated" diseases, including autoimmunity and allergy. Objective We sought to test whether the change of gut microbiota with the broad spectrum antibiotic enrofloxacin will modulate contact sensitivity (CS) in mice. Methods Natural gut microbiota were modified by oral treatment with enrofloxacin prior to sensitization with Trinitrophenyl chloride followed by CS testing. Finally, adoptive cell transfers were performed to characterize the regulatory cells that are induced by microbiota modification. Results Oral treatment with enrofloxacin suppresses CS and production of anti–Trinitrophenyl chloride IgG1 antibodies. Adoptive transfer experiments show that antibiotic administration favors induction of regulatory cells that suppress CS. Flow cytometry and adoptive transfer of purified cells show that antibiotic-induced suppression of CS is mediated by TCR αβ + CD4 + CD25 + FoxP3 + Treg, CD19 + B220 + CD5 + IL-10 + , IL-10 + Tr1, and IL-10 + TCR γδ + cells. Treatment with the antibiotic induces dysbiosis characterized by increased proportion of Clostridium coccoides (cluster XIVa), C coccoides – Eubacterium rectale (cluster XIVab), Bacteroidetes, and Bifidobacterium spp, but decreased segmented filamentous bacteria. Transfer of antibiotic-modified gut microbiota inhibits CS, but this response can be restored through oral transfer of control gut bacteria to antibiotic-treated animals. Conclusions Oral treatment with a broad spectrum antibiotic modifies gut microbiota composition and promotes anti-inflammatory response, suggesting that manipulation of gut microbiota can be a powerful tool to modulate the course of CS.
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broad spectrum antibiotic enrofloxacin modulates contact sensitivity through gut microbiota in a murine model
The Journal of Allergy and Clinical Immunology, 2017Co-Authors: Anna Strzepa, Monika Majewskaszczepanik, Francis M Lobo, Li Wen, Marian SzczepanikAbstract:Background Medical advances in the field of infection therapy have led to an increasing use of antibiotics, which, apart from eliminating pathogens, also partially eliminate naturally existing commensal bacteria. It has become increasingly clear that less exposure to microbiota early in life may contribute to the observed rise in "immune-mediated" diseases, including autoimmunity and allergy. Objective We sought to test whether the change of gut microbiota with the broad spectrum antibiotic enrofloxacin will modulate contact sensitivity (CS) in mice. Methods Natural gut microbiota were modified by oral treatment with enrofloxacin prior to sensitization with Trinitrophenyl chloride followed by CS testing. Finally, adoptive cell transfers were performed to characterize the regulatory cells that are induced by microbiota modification. Results Oral treatment with enrofloxacin suppresses CS and production of anti–Trinitrophenyl chloride IgG1 antibodies. Adoptive transfer experiments show that antibiotic administration favors induction of regulatory cells that suppress CS. Flow cytometry and adoptive transfer of purified cells show that antibiotic-induced suppression of CS is mediated by TCR αβ + CD4 + CD25 + FoxP3 + Treg, CD19 + B220 + CD5 + IL-10 + , IL-10 + Tr1, and IL-10 + TCR γδ + cells. Treatment with the antibiotic induces dysbiosis characterized by increased proportion of Clostridium coccoides (cluster XIVa), C coccoides – Eubacterium rectale (cluster XIVab), Bacteroidetes, and Bifidobacterium spp, but decreased segmented filamentous bacteria. Transfer of antibiotic-modified gut microbiota inhibits CS, but this response can be restored through oral transfer of control gut bacteria to antibiotic-treated animals. Conclusions Oral treatment with a broad spectrum antibiotic modifies gut microbiota composition and promotes anti-inflammatory response, suggesting that manipulation of gut microbiota can be a powerful tool to modulate the course of CS.
