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 Citations (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.

Original language	English
Article number	16140
Journal	Nature Microbiology
Volume	1
Issue number	11
Pages (from-to)	1-13
Number of pages	13
ISSN	2058-5276
DOIs	https://doi.org/10.1038/nmicrobiol.2016.140
Publication status	Published - 22 Aug 2016

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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. Article 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, vol. 1, no. 11, 16140, pp. 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.",

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AU - Kim, Joanne

AU - Ng, Sandy

AU - Rogers, Arlin B

AU - Sumner, Susan

AU - Zhang, Xue-Song

AU - Cadwell, Ken

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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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