Antibiotic-mediated gut microbiome perturbation accelerates development of type 1 diabetes in mice

Alexandra E Livanos; Thomas U Greiner; Pajau Vangay; Wimal Pathmasiri; Delisha Stewart; Susan McRitchie; Huilin Li; Jennifer Chung; Jiho Sohn; Sara Kim; Zhan Gao; Cecily Barber; Joanne Kim; Sandy Ng; Arlin B Rogers; Susan Sumner; Xue-Song Zhang; Ken Cadwell; Dan Knights; Alexander Alekseyenko; Gert Fredrik Bäckhed; Martin J Blaser

doi:10.1038/nmicrobiol.2016.140

Antibiotic-mediated gut microbiome perturbation accelerates development of type 1 diabetes in mice

Alexandra E Livanos, Thomas U Greiner, Pajau Vangay, Wimal Pathmasiri, Delisha Stewart, Susan McRitchie, Huilin Li, Jennifer Chung, Jiho Sohn, Sara Kim, Zhan Gao, Cecily Barber, Joanne Kim, Sandy Ng, Arlin B Rogers, Susan Sumner, Xue-Song Zhang, Ken Cadwell, Dan Knights, Alexander AlekseyenkoGert Fredrik Bäckhed, Martin J Blaser

163 Citationer (Scopus)

Abstract

The early life microbiome plays important roles in host immunological and metabolic development. Because the incidence of type 1 diabetes (T1D) has been increasing substantially in recent decades, we hypothesized that early-life antibiotic use alters gut microbiota, which predisposes to disease. Using non-obese diabetic mice that are genetically susceptible to T1D, we examined the effects of exposure to either continuous low-dose antibiotics or pulsed therapeutic antibiotics (PAT) early in life, mimicking childhood exposures. We found that in mice receiving PAT, T1D incidence was significantly higher, and microbial community composition and structure differed compared with controls. In pre-diabetic male PAT mice, the intestinal lamina propria had lower Th17 and T reg proportions and intestinal SAA expression than in controls, suggesting key roles in transducing the altered microbiota signals. PAT affected microbial lipid metabolism and host cholesterol biosynthetic gene expression. These findings show that early-life antibiotic treatments alter the gut microbiota and its metabolic capacities, intestinal gene expression and T-cell populations, accelerating T1D onset in non-obese diabetic mice. ' 2016 Macmillan Publishers Limited, part of Springer Nature.

Originalsprog	Engelsk
Artikelnummer	16140
Tidsskrift	Nature Microbiology
Vol/bind	1
Udgave nummer	11
Sider (fra-til)	1-13
Antal sider	13
ISSN	2058-5276
DOI	https://doi.org/10.1038/nmicrobiol.2016.140
Status	Udgivet - 22 aug. 2016

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10.1038/nmicrobiol.2016.140

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Livanos, A. E., Greiner, T. U., Vangay, P., Pathmasiri, W., Stewart, D., McRitchie, S., Li, H., Chung, J., Sohn, J., Kim, S., Gao, Z., Barber, C., Kim, J., Ng, S., Rogers, A. B., Sumner, S., Zhang, X-S., Cadwell, K., Knights, D., ... Blaser, M. J. (2016). Antibiotic-mediated gut microbiome perturbation accelerates development of type 1 diabetes in mice. Nature Microbiology, 1(11), 1-13. [16140]. https://doi.org/10.1038/nmicrobiol.2016.140

Livanos, AE, Greiner, TU, Vangay, P, Pathmasiri, W, Stewart, D, McRitchie, S, Li, H, Chung, J, Sohn, J, Kim, S, Gao, Z, Barber, C, Kim, J, Ng, S, Rogers, AB, Sumner, S, Zhang, X-S, Cadwell, K, Knights, D, Alekseyenko, A, Bäckhed, GF & Blaser, MJ 2016, 'Antibiotic-mediated gut microbiome perturbation accelerates development of type 1 diabetes in mice', Nature Microbiology, bind 1, nr. 11, 16140, s. 1-13. https://doi.org/10.1038/nmicrobiol.2016.140

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abstract = "The early life microbiome plays important roles in host immunological and metabolic development. Because the incidence of type 1 diabetes (T1D) has been increasing substantially in recent decades, we hypothesized that early-life antibiotic use alters gut microbiota, which predisposes to disease. Using non-obese diabetic mice that are genetically susceptible to T1D, we examined the effects of exposure to either continuous low-dose antibiotics or pulsed therapeutic antibiotics (PAT) early in life, mimicking childhood exposures. We found that in mice receiving PAT, T1D incidence was significantly higher, and microbial community composition and structure differed compared with controls. In pre-diabetic male PAT mice, the intestinal lamina propria had lower Th17 and T reg proportions and intestinal SAA expression than in controls, suggesting key roles in transducing the altered microbiota signals. PAT affected microbial lipid metabolism and host cholesterol biosynthetic gene expression. These findings show that early-life antibiotic treatments alter the gut microbiota and its metabolic capacities, intestinal gene expression and T-cell populations, accelerating T1D onset in non-obese diabetic mice. ' 2016 Macmillan Publishers Limited, part of Springer Nature.",

author = "Livanos, {Alexandra E} and Greiner, {Thomas U} and Pajau Vangay and Wimal Pathmasiri and Delisha Stewart and Susan McRitchie and Huilin Li and Jennifer Chung and Jiho Sohn and Sara Kim and Zhan Gao and Cecily Barber and Joanne Kim and Sandy Ng and Rogers, {Arlin B} and Susan Sumner and Xue-Song Zhang and Ken Cadwell and Dan Knights and Alexander Alekseyenko and B{\"a}ckhed, {Gert Fredrik} and Blaser, {Martin J}",

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AU - McRitchie, Susan

AU - Li, Huilin

AU - Chung, Jennifer

AU - Sohn, Jiho

AU - Kim, Sara

AU - Gao, Zhan

AU - Barber, Cecily

AU - Kim, Joanne

AU - Ng, Sandy

AU - Rogers, Arlin B

AU - Sumner, Susan

AU - Zhang, Xue-Song

AU - Cadwell, Ken

AU - Knights, Dan

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AU - Bäckhed, Gert Fredrik

AU - Blaser, Martin J

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N2 - The early life microbiome plays important roles in host immunological and metabolic development. Because the incidence of type 1 diabetes (T1D) has been increasing substantially in recent decades, we hypothesized that early-life antibiotic use alters gut microbiota, which predisposes to disease. Using non-obese diabetic mice that are genetically susceptible to T1D, we examined the effects of exposure to either continuous low-dose antibiotics or pulsed therapeutic antibiotics (PAT) early in life, mimicking childhood exposures. We found that in mice receiving PAT, T1D incidence was significantly higher, and microbial community composition and structure differed compared with controls. In pre-diabetic male PAT mice, the intestinal lamina propria had lower Th17 and T reg proportions and intestinal SAA expression than in controls, suggesting key roles in transducing the altered microbiota signals. PAT affected microbial lipid metabolism and host cholesterol biosynthetic gene expression. These findings show that early-life antibiotic treatments alter the gut microbiota and its metabolic capacities, intestinal gene expression and T-cell populations, accelerating T1D onset in non-obese diabetic mice. ' 2016 Macmillan Publishers Limited, part of Springer Nature.

AB - The early life microbiome plays important roles in host immunological and metabolic development. Because the incidence of type 1 diabetes (T1D) has been increasing substantially in recent decades, we hypothesized that early-life antibiotic use alters gut microbiota, which predisposes to disease. Using non-obese diabetic mice that are genetically susceptible to T1D, we examined the effects of exposure to either continuous low-dose antibiotics or pulsed therapeutic antibiotics (PAT) early in life, mimicking childhood exposures. We found that in mice receiving PAT, T1D incidence was significantly higher, and microbial community composition and structure differed compared with controls. In pre-diabetic male PAT mice, the intestinal lamina propria had lower Th17 and T reg proportions and intestinal SAA expression than in controls, suggesting key roles in transducing the altered microbiota signals. PAT affected microbial lipid metabolism and host cholesterol biosynthetic gene expression. These findings show that early-life antibiotic treatments alter the gut microbiota and its metabolic capacities, intestinal gene expression and T-cell populations, accelerating T1D onset in non-obese diabetic mice. ' 2016 Macmillan Publishers Limited, part of Springer Nature.

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Antibiotic-mediated gut microbiome perturbation accelerates development of type 1 diabetes in mice

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