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Ratio of Klebsiella/Bifidobacterium in early life correlates with later development of paediatric allergy

In: Beneficial Microbes
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J.S.Y. Low Nutricia Research, Danone Nutricia Early Life Nutrition, Matrix Building #05-01B, 30 Biopolis Street, 138671 Singapore, Singapore.

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S.-E. Soh Singapore Institute for Clinical Sciences, Agency for Science and Technology Research (A*STAR), 30 Medical Drive, 117609, Singapore, Singapore.
Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, 5 Science drive 2, 117597, Singapore, Singapore.

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Y.K. Lee Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, 5 Science drive 2, 117597, Singapore, Singapore.

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K.Y.C. Kwek KK Women’s and Children’s Hospital, Singapore, Singapore.

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J.D. Holbrook Singapore Institute for Clinical Sciences, Agency for Science and Technology Research (A*STAR), 30 Medical Drive, 117609, Singapore, Singapore.
Human Development & Health Academic Unit, University of Southampton & NIHR Southampton Biomedical Research Centre, University of Southampton & University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton, SO16 6YD, UK.

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E.M. Van der Beek Nutricia Research, Uppsalalaan 12, 3584 CT, Utrecht, the Netherlands.
Department of Pediatrics, University Medical Centre Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, the Netherlands.

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L.P. Shek Singapore Institute for Clinical Sciences, Agency for Science and Technology Research (A*STAR), 30 Medical Drive, 117609, Singapore, Singapore.
Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, 5 Science drive 2, 117597, Singapore, Singapore.

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A.E.N. Goh KK Women’s and Children’s Hospital, Singapore, Singapore.

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O.H. Teoh KK Women’s and Children’s Hospital, Singapore, Singapore.

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K.M. Godfrey MRC Lifecourse Epidemiology Unit, and NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Tremona Road, SO16 6YD Southampton, United Kingdom.

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Y.-S. Chong Singapore Institute for Clinical Sciences, Agency for Science and Technology Research (A*STAR), 30 Medical Drive, 117609, Singapore, Singapore.
Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, 5 Science drive 2, 117597 Singapore, Singapore.

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J. Knol Nutricia Research, Uppsalalaan 12, 3584 CT, Utrecht, the Netherlands.
Laboratory of Microbiology, Wageningen University, P.O. Box 7005, 6700 CA, Wageningen, the Netherlands.

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C. Lay Nutricia Research, Danone Nutricia Early Life Nutrition, Matrix Building #05-01B, 30 Biopolis Street, 138671 Singapore, Singapore.
Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, 5 Science drive 2, 117597, Singapore, Singapore.

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Several studies have reported that intestinal microbial colonisation patterns differ between non-allergic and allergic infants. However, the microbial signature underlying the pathogenesis of allergies remains unclear. We aim to gain insight into the development of the intestinal microbiota of healthy infants and infants who develop allergy in early life, and identify potential microbiota biomarkers of later allergic disease. Using a case-control design in a Chinese sub-cohort of a Singaporean birth cohort (GUSTO), we utilised 16S rRNA gene sequencing to assess intestinal microbial composition and diversity of 21 allergic and 18 healthy infants at 3 weeks, 3 months and 6 months of age, and correlated the microbiota with allergy at ages 18 and 36 months. Pronounced differences in intestinal microbiota composition between allergic and healthy infants were observed at 3 months of age. The intestine of healthy infants was colonised with higher abundance of commensal Bifidobacterium. Conversely, Klebsiella, an opportunistic pathogen, was significantly enriched in the allergic infants. Interestingly, infants with a high Klebsiella/Bifidobacterium (K/B) ratio (above the population median K/B ratio) at age 3 months had an odds ratio of developing allergy by 3 years of age of 9.00 (95% confidence interval 1.46-55.50) compared to those with low K/B ratio. This study demonstrated a relationship between the ratio of genera Klebsiella and Bifidobacterium during early infancy and development of paediatric allergy in childhood. Our study postulates that an elevated K/B ratio in early infancy could be a potential indicator of an increased risk of allergy development. This line of research might enable future intervention strategies in early life to prevent or treat allergy. Our study provides new insights into microbial signatures associated with childhood allergy, in particular, suggests that an elevated K/B ratio could be a potential early-life microbiota biomarker of allergic disease.

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