Association between Intrauterine Microbiome and Risk of Intrauterine Growth Restriction: A Case-Control Study Based on Guangxi Zhuang Birth Cohort in China

Substantial evidence show that intrauterine growth restriction (IUGR) is linked to both short-term and longterm health consequences. Recent studies have shown that the intrauterine environment harbors a diverse community of microbes. However, the relationship between intrauterine microbiome and IUGR has been rarely studied. In our investigation of 35 neonates with IUGR and 187 neonates without IUGR, we found that the intrauterine microbiome was largely composed of nonpathogenic commensal microbiota from the Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes phyla. Carriage of genera Afipia [odds ratio (OR) 0.24; 95% confidence interval (CI) 0.10-0.60], Hydrogenophaga (OR 0.10; 95% CI 0.01-0.76), and Perlucidibaca (OR 0.25; 95% CI 0.10-0.61) were significantly associated with decreased risk of IUGR, while one log10-unit increasing of relative abundance the genera Catenibacterium (OR 2.56; 95% CI 1.09-6.01) and Senegalimassilia (OR 1.78; 95% CI 1.00-3.16), and carriage of Holdemanella (OR 4.07; 95% CI 1.5410.76), Parvimonas (OR 3.33; 95% CI 1.16-9.57), Sandaracinus (OR 3.27; 95% CI 1.21- 8.84), and Streptococcus (OR 3.52; 95% CI 1.13-10.95) were associated with increased risk of IUGR. The present study firstly demonstrated that carriage of Afipia, Hydrogenophaga, and Perlucidibaca in the intrauterine environment is associated with a decreased risk of IUGR, while carriage of Holdemanella, Parvimonas, Sandaracinus, and Streptococcus, and increased relative abundance of Catenibacterium and Senegalimassilia are associated with an increased risk of IUGR. The study provides evidence that the intrauterine microbiome may play a role in the etiology of IUGR.