Gram-Negative Colonization and Bacterial Translocation Drive Neonatal Sepsis in the Indian Setting

Abstract

Background: The gut microbiota, comprising billions of microorganisms, plays a pivotal role in health and disease. This study aims to investigate the effect of sepsis on gut microbiome of neonates admitted to the Neonatal Intensive Care Unit.

Methods: A prospective cohort study was carried out in the NICU of tertiary care hospital in Karnataka, India, from January 2021 to September 2023. Preterm neonates with birth weight < 1500 g and gestational age < 37 weeks were recruited, excluding those with congenital gastrointestinal anomalies, necrotizing enterocolitis, or blood culture-negative infections. The study population was divided into three groups: healthy neonates (Group A), neonates with drug-sensitive GNB sepsis (Group B), and neonates with pan drug-resistant GNB sepsis (Group C). Stool samples were collected aseptically, snapped in liquid nitrogen, and stored at -80⁰C for extraction of DNA and microbiome analysis.

Results: The gut microbiota of healthy neonates (Group A) was dominated by Proteobacteria (24.04%), Actinobacteria (27.13%), Firmicutes (12.74%), and Bacteroidetes (3%). Predominant genera included Bifidobacterium (55.17%), Enterobacter (12.55%), Enterococcus (50.69%), Streptococcus (7.92%), and Bacteroides (3.58%).Groups B and C, the microbiota exhibited higher Proteobacteria abundance (57.16% and 66.58%, respectively) and reduced diversity of beneficial bacteria. Notably, the presence of sepsis was associated with an increase in pathogenic bacteria and a decrease in beneficial commensal bacteria.

Conclusion: Neonates with sepsis exhibited significant gut microbiome dysbiosis, characterized by increased Proteobacteria and reduced beneficial bacteria diversity. These findings highlight the potential of microbiome profiling as a diagnostic tool and underscore the importance of gut microbiota modulation in managing neonatal sepsis.

Keywords: Dysbiosis; Gut microbiome; Microbial colonization; Neonatal sepsis; Preterm infants; Proteobacteria.

Fig. 1

Concept of modulating gut microbiota

Fig. 2

Outline of the methodology

Fig. 3

Microbial α-diversity indexes. Box plots depict differences in the fecal microbiome diversity indexes between the sepsis and control groups according to the Shannon index based on the OTU count

Fig. 4

Differences in microbial composition in the three groups. A Nonmetric multidimensional scaling (NMDS) of the Whites-nonparametric-t-test indexes of samples is shown

Fig. 5

High correlation microbiota composition and pathogens identified by sequencing. Each bar represent the microbiota composition of each of the group of at genus level