# P-1550. Early Infant Gut Dysbiosis Associated with Extended-Spectrum Beta-Lactamase Producing Escherichia coli (ESBL-EC) Colonization in a Low-Resource Setting

## TL;DR

This study finds that infants colonized with antibiotic-resistant Escherichia coli have gut imbalances and are more likely to be underweight in a low-resource setting.

## Contribution

The study reveals a link between ESBL-producing E. coli colonization in infants and gut dysbiosis, reduced microbial diversity, and increased risk of underweight status.

## Key findings

- Infants colonized with ESBL-EC had higher E. coli abundance and lower commensal bacteria like Prevotella copri and Bifidobacterium longum.
- ESBL-positive infants at 3 months were 3.47 times more likely to be underweight compared to infants of ESBL-negative mothers.
- Gut microbial diversity was significantly lower in ESBL-positive maternal and 3-month infant samples compared to non-ESBL samples.

## Abstract

In vitro and in vivo studies have shown that Extended-Spectrum Beta-Lactamase-producing Escherichia coli (ESBL-EC) can out-compete non-resistant commensals. The rapidly developing infant gut microbiome is susceptible to colonization with ESBL-EC, which may displace commensals leading to dysbiosis. Gut dysbiosis is linked to growth impairment in infancy, especially in low-resource settings. We aimed to investigate the interplay of ESBL-EC colonization, gut microbiome and infant growth among Pakistani mother-infant dyads.Figure 1:Percentage distribution of samples according to ESBL positivityThe majority of infant samples were positive for ESBL genes (ESBL positive). Whereas most maternal samples either carried non-ESBL beta-lactamases (Non-ESBL positive) or carried no beta-lactamases (BL negative).Figure 2:Shannon Diversity IndexShannon diversity index of microbial communities in relation to the presence or absence of ESBL and non-ESBL beta-lactamase genes among maternal and infants samples is shown.

Percentage distribution of samples according to ESBL positivity

The majority of infant samples were positive for ESBL genes (ESBL positive). Whereas most maternal samples either carried non-ESBL beta-lactamases (Non-ESBL positive) or carried no beta-lactamases (BL negative).

Shannon Diversity Index

Shannon diversity index of microbial communities in relation to the presence or absence of ESBL and non-ESBL beta-lactamase genes among maternal and infants samples is shown.

We utilized the Alliance for Maternal and Newborn Health Improvement (AMANHI) biorepository, which enrolled participants in a Pakistani community. Maternal and 3- and 12-month infant stool from 350 dyads underwent shotgun sequencing. Anthropometry was recorded, z-scores calculated, and odds ratios estimated using the elrm package in R.Figure 3:Principal Coordinates Analysis (PCoA) plot for β-diversity using the Bray-Curtis dissimilarity metricMaternal and 3-month infant ESBL positive samples showed a distinct pattern of clustering compared to the other non-ESBL BL positive samples and BL negative samples. At 12-months there was greater overlap between the three groups.

Principal Coordinates Analysis (PCoA) plot for β-diversity using the Bray-Curtis dissimilarity metric

Maternal and 3-month infant ESBL positive samples showed a distinct pattern of clustering compared to the other non-ESBL BL positive samples and BL negative samples. At 12-months there was greater overlap between the three groups.

ESBL gene positivity (ESBL-pos) among maternal and 3- and 12-month infants was 46.9%, 82.8%, and 78.2%, respectively (Figure 1). Maternal ESBL-pos samples had significantly lower α-diversity compared to non-ESBL BL samples (p=0.005), while 3-month infant ESBL-pos samples had higher diversity than BL negative samples (p=< 0.001). In contrast, among 12-month infants, no significant difference was observed between any group (Figure 2). Principal Coordinates Analysis (PCoA) plots for β-diversity revealed distinct clustering of ESBL-pos samples among mothers and their 3-month-old infants compared to the non-ESBL BL and BL-neg groups (PERMANOVA p = 1e-04). By 12-months, we noted greater overlap these groups, though the clusters remained significantly different (PERMANOVA p = 0.0273, Figure 3). In both maternal and infant samples, ESBL-pos was associated with significant increase in E. coli abundance and decrease in commensals such as Prevotella copri and Bifidobacterium longum. After controlling for confounders, the odds of an infant born to ESBL-pos mothers being underweight at 3 months was 3.47 times that of an infant born to ESBL-neg mothers (95% Confidence Interval: (1.01, 19.3); p = 0.03).

ESBL-positivity is associated with increased E. coli abundance, reduced commensals, altered gut microbial diversity, and underweight status in infants.

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