Chiavaroli, Valentina

Cutfield, Wayne

Derraik, José

Ekblad, Cameron

Hofman, Paul

Jayasinghe, Thilini N.

McKenzie, Elizabeth

O’Sullivan, Justin

Sachin, Jayan

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DOHaD研究 (ISSN 2187-2597) 
2016年 第 5巻 第 1号 19頁 
 
  
The gut microbiome and insulin resistance in children born preterm 
 
Thilini N. Jayasinghe*
1
, Valentina Chiavaroli*
1,2
, Sachin Jayan
1
, Cameron Ekblad
1, 
José 
Derraik
1
, Paul Hofman
1,2
, Elizabeth McKenzie
1
, Wayne Cutfield
1,2
, Justin O’Sullivan1,2 
*contributed equally to this work 
1 
Liggins Institute, University of Auckland, New Zealand 
2 
Gravida: National Centre for Growth and Development, New Zealand 
 
Background: There is increasing evidence that the gut microbiome influences the 
development of obesity and type 2 diabetes. Studies also show that preterm children are 
at increased risk for insulin resistance, obesity, and cardiovascular disease. We 
hypothesized that adverse early life events in preterm infants may lead to alterations in 
the gut microbiome, which negatively affect metabolism later in life.  
Aim: To examine the association between metabolic phenotype with the gut microbiome 
composition and functional capacity in healthy prepubertal children born very preterm 
(<32 weeks of gestation; n=51) compared to those born at term (37–41 weeks; n=50).  
Results: Participants were healthy prepubertal children aged 5 to 10 years born very 
preterm (<32 weeks of gestation; n=51) and at term (37–41 weeks; n=50). Children 
born very preterm were younger (7.8±1.4 vs 8.3±1.4 years; p=0.034) than peers born at 
term. No difference were observed in sex ratio (p=0.90) between the two groups. Preterm 
children were shorter (height SDS 0.31 vs 0.92; p=0.0006) and leaner (BMI SDS -0.20 vs 
0.29; p<0.0001) than those born at term. Importantly, after adjustment for adiposity and 
other confounders, children born very preterm had lower insulin sensitivity than term 
controls (9.2 vs 12.5 x10
-4
·min
-1
(mU/l); p=0.0007). Stool metatranscriptomics identified 
Collinsella species as being significantly associated with children who were born 
preterm (highly significant with LDA score >4.0, LefSe). There were also functional 
changes in the activity of the microbiome in children born preterm, including glutamate 
and arginine metabolism, known to be involved in glucose homeostasis. Changes to the 
metabolites within the preterm fecal and plasma correlated with the observed 
phenotypes. 
Conclusion: Children born very preterm have reduced insulin sensitivity and display 
differences in gut microbiome species and activity. We speculate that (i) these changes 
in the gut microbiome of children born preterm were established in early infancy, and 
(ii) the altered gut microbiome contributes to insulin resistance. 
 


The gut microbiome and insulin resistance in children born preterm

http://hikumano.hama-med.ac.jp/dspace/bitstream/10271/3083/1/dohad-5-1-19.pdf

The gut microbiome and insulin resistance in children born preterm

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