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Implications of gut microbiota in the association between infant antibiotic exposure and childhood obesity and adiposity accumulation

Implications of gut microbiota in the association between infant antibiotic exposure and childhood obesity and adiposity accumulation
Implications of gut microbiota in the association between infant antibiotic exposure and childhood obesity and adiposity accumulation
Background In animal studies early life antibiotic exposure causes metabolic abnormalities including obesity through microbiota disruption, but evidence from human studies is scarce. We examined involvement of gut microbiota in the associations between infant antibiotic exposure and childhood adiposity. Methods Infant antibiotic exposure in the first year of life was ascertained using parental reports during interviewer-administered questionnaires. Primary outcomes were childhood obesity [body mass index (BMI) z-score > 95th percentile] and adiposity [abdominal circumference (AC) and skinfold (triceps + subscapular (SST)) measurements] determined from ages 15–60 months. At age 24 months, when the gut microbiota are more stable, stool samples (n = 392) were collected for the gut microbiota profiling using co-abundancy networks. Associations of antibiotic exposure with obesity and adiposity (n = 1016) were assessed using multiple logistic and linear mixed effects regressions. Key bacteria associated with antibiotics exposure were identified by partial redundancy analysis and multivariate association with linear models. Results Antibiotic exposure was reported in 38% of study infants. In a fully adjusted model, a higher odds of obesity from 15–60 months of age was observed for any antibiotic exposure [OR(95% CI) = 1.45(1.001, 2.14)] and exposure to ≥3 courses of antibiotics [2.78(1.12, 6.87)]. For continuous adiposity indicators, any antibiotic exposure was associated with higher BMI z-score in boys [β = 0.15(0.01, 0.28)] but not girls [β = −0.04(−0.19, 0.11)] (P interaction = 0.026). Similarly, exposure to ≥3 courses of antibiotics was associated with higher AC in boys [1.15(0.05, 2.26) cm] but not girls [0.57(−1.32, 2.45) cm] (P interaction not significant). Repeated exposure to antibiotics was associated with a significant reduction (FDR-corrected P values < 0.05) in a microbial co-abundant group (CAG) represented by Eubacterium hallii, whose proportion was negatively correlated with childhood adiposity. Meanwhile, a CAG represented by Tyzzerella 4 was positively correlated with the repeated use of antibiotics and childhood adiposity. Conclusions Infant antibiotic exposure was associated with disruption of the gut microbiota and the higher risks of childhood obesity and increased adiposity.
0307-0565
1508-1520
Chen, Ling-Wei
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Xu, Jia
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Soh, S.E.
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Aris, I.M.
ee15a46e-ead3-4b4a-a208-d39038a85480
Mya, Tint
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Gluckman, Peter D.
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Tan, Kok Hian
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Shek, Lynette P.
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Chong, Yap-Seng
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Yap, Fabian
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Godfrey, Keith
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Gilbert, Jack A.
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Karnani, Neerja
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Lee, Yung Seng
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Chen, Ling-Wei
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Xu, Jia
d3a9a6ae-89a2-4481-9ff8-ec793f5f8dea
Soh, S.E.
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Aris, I.M.
ee15a46e-ead3-4b4a-a208-d39038a85480
Mya, Tint
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Gluckman, Peter D.
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Tan, Kok Hian
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Shek, Lynette P.
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Chong, Yap-Seng
7043124b-e892-4d4b-8bb7-6d35ed94e136
Yap, Fabian
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Godfrey, Keith
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Gilbert, Jack A.
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Karnani, Neerja
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Lee, Yung Seng
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Chen, Ling-Wei, Xu, Jia, Soh, S.E., Aris, I.M., Mya, Tint, Gluckman, Peter D., Tan, Kok Hian, Shek, Lynette P., Chong, Yap-Seng, Yap, Fabian, Godfrey, Keith, Gilbert, Jack A., Karnani, Neerja and Lee, Yung Seng (2020) Implications of gut microbiota in the association between infant antibiotic exposure and childhood obesity and adiposity accumulation. International Journal of Obesity, 44 (7), 1508-1520. (doi:10.1038/s41366-020-0572-0).

Record type: Article

Abstract

Background In animal studies early life antibiotic exposure causes metabolic abnormalities including obesity through microbiota disruption, but evidence from human studies is scarce. We examined involvement of gut microbiota in the associations between infant antibiotic exposure and childhood adiposity. Methods Infant antibiotic exposure in the first year of life was ascertained using parental reports during interviewer-administered questionnaires. Primary outcomes were childhood obesity [body mass index (BMI) z-score > 95th percentile] and adiposity [abdominal circumference (AC) and skinfold (triceps + subscapular (SST)) measurements] determined from ages 15–60 months. At age 24 months, when the gut microbiota are more stable, stool samples (n = 392) were collected for the gut microbiota profiling using co-abundancy networks. Associations of antibiotic exposure with obesity and adiposity (n = 1016) were assessed using multiple logistic and linear mixed effects regressions. Key bacteria associated with antibiotics exposure were identified by partial redundancy analysis and multivariate association with linear models. Results Antibiotic exposure was reported in 38% of study infants. In a fully adjusted model, a higher odds of obesity from 15–60 months of age was observed for any antibiotic exposure [OR(95% CI) = 1.45(1.001, 2.14)] and exposure to ≥3 courses of antibiotics [2.78(1.12, 6.87)]. For continuous adiposity indicators, any antibiotic exposure was associated with higher BMI z-score in boys [β = 0.15(0.01, 0.28)] but not girls [β = −0.04(−0.19, 0.11)] (P interaction = 0.026). Similarly, exposure to ≥3 courses of antibiotics was associated with higher AC in boys [1.15(0.05, 2.26) cm] but not girls [0.57(−1.32, 2.45) cm] (P interaction not significant). Repeated exposure to antibiotics was associated with a significant reduction (FDR-corrected P values < 0.05) in a microbial co-abundant group (CAG) represented by Eubacterium hallii, whose proportion was negatively correlated with childhood adiposity. Meanwhile, a CAG represented by Tyzzerella 4 was positively correlated with the repeated use of antibiotics and childhood adiposity. Conclusions Infant antibiotic exposure was associated with disruption of the gut microbiota and the higher risks of childhood obesity and increased adiposity.

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Accepted/In Press date: 26 March 2020
e-pub ahead of print date: 22 April 2020

Identifiers

Local EPrints ID: 440845
URI: http://eprints.soton.ac.uk/id/eprint/440845
ISSN: 0307-0565
PURE UUID: 20b8e022-d231-407d-94da-d2e20b856b0b
ORCID for Keith Godfrey: ORCID iD orcid.org/0000-0002-4643-0618

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Date deposited: 20 May 2020 16:31
Last modified: 26 Nov 2021 05:18

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Contributors

Author: Ling-Wei Chen
Author: Jia Xu
Author: S.E. Soh
Author: I.M. Aris
Author: Tint Mya
Author: Peter D. Gluckman
Author: Kok Hian Tan
Author: Lynette P. Shek
Author: Yap-Seng Chong
Author: Fabian Yap
Author: Keith Godfrey ORCID iD
Author: Jack A. Gilbert
Author: Neerja Karnani
Author: Yung Seng Lee

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