Early-life gut microbiome modulation reduces the abundance of antibiotic-resistant bacteria

Abstract

Background Antibiotic-resistant (AR) bacteria are a global threat. AR bacteria can be acquired in early life and have long-term sequelae. Limiting the spread of antibiotic resistance without triggering the development of additional resistance mechanisms is of immense clinical value. Here, we show how the infant gut microbiome can be modified, resulting in a significant reduction of AR genes (ARGs) and the potentially pathogenic bacteria that harbor them. Methods The gut microbiome was characterized using shotgun metagenomics of fecal samples from two groups of healthy, term breastfed infants. One group was fed B. infantis EVC001 in addition to receiving lactation support ( n = 29, EVC001-fed), while the other received lactation support alone ( n = 31, controls). Coliforms were isolated from fecal samples and genome sequenced, as well as tested for minimal inhibitory concentrations against clinically relevant antibiotics. Results Infants fed B. infantis EVC001 exhibited a change to the gut microbiome, resulting in a 90% lower level of ARGs compared to controls. ARGs that differed significantly between groups were predicted to confer resistance to beta lactams, fluoroquinolones, or multiple drug classes, the majority of which belonged to Escherichia , Clostridium, and Staphylococcus . Minimal inhibitory concentration assays confirmed the resistance phenotypes among isolates with these genes. Notably, we found extended-spectrum beta lactamases among healthy, vaginally delivered breastfed infants who had never been exposed to antibiotics. Conclusions Colonization of the gut of breastfed infants by a single strain of B. longum subsp. infantis had a profound impact on the fecal metagenome, including a reduction in ARGs. This highlights the importance of developing novel approaches to limit the spread of these genes among clinically relevant bacteria. Future studies are needed to determine whether colonization with B. infantis EVC001 decreases the incidence of AR infections in breastfed infants. Trial registration This clinical trial was registered at ClinicalTrials.gov , NCT02457338. Electronic supplementary material The online version of this article (10.1186/s13756-019-0583-6) contains supplementary material, which is available to authorized users.

The Infant Gut Resistome is Associated with E. coli and Early-life Exposures

“…Our ndings agree with other studies that have identi ed Proteobacteria [13,15,19,36,37] and speci cally E. coli [13,19,37] as signi cant sources of ARGs. While it could be argued that these results are a consequence of identi ed ARGs, it is worth noting that studies across different species and ecosystems using qPCR or assembly-based methods have also identi ed that Proteobacteria harbor a proportionately high level of ARGs [40,41].…”

“…To determine the in uence of microbial composition on resistome composition, we taxonomically pro led the infant stool samples using MetaPhlAn2 [35]. As previous research has identi ed Proteobacteria abundance to be associated with certain ARGs [13,15,19,36,37] and we visually examined and identi ed Proteobacteria to be correlated with the relative abundance of the resistome (Figure 1c), we focused on this taxon as a potential mediator between infant characteristics and resistome composition.…”

Colonization Resistance in the Infant Gut: The Role of B. infantis in Reducing pH and Preventing Pathogen Growth

“…infantis (B. infantis), which is conspicuously absent in industrialized nations [8][9][10]. In the United States, the microbiome of babies born today are not dominated by Bifidobacterium, and most notably is the lack of B. infantis, specifically [11,12]. Consequently, important ecosystem services of the microbiome are lost, which in turn leads to low community stability and diminished colonization resistance, which together are signatures of infant gut dysbiosis [13].…”

Integrating the Ecosystem Services Framework to Define Dysbiosis of the Breastfed Infant Gut: The Role of B. infantis and Human Milk Oligosaccharides

“…Thus, higher diversity is often assumed to be desirable. However, unless substantial functional redundancy exists in a microbial community, any loss in key functional species will likely alter the capacity of the microbiome to support ecosystem services (44). Further, a reduction in diversity is not necessarily unfavorable to the host, especially when it is a consequence of the selective enrichment of health-promoting symbionts.…”