Gut microbiome signatures of nursing home residents carrying Enterobacteria Producing Extended-spectrum β-lactamases

Abstract

Background The prevalence of extended beta-lactamase producing Enterobacteriaceae (ESBL-E) has been constantly increasing over the last decades. These microorganisms that have acquired broad antibiotic resistance are now common human pathogens. Changes in the gut microbiome, induced by antibiotics or other drugs, enable expansion of these microorganisms, but the mechanisms are not yet fully understood. Objectives To investigate taxonomic and functional characteristics of the gut microbiome of nursing home residents carrying ESBL-E using metagenomics. Patients and methods We included 144 residents living in two different nursing homes. All fecal samples were screened for ESBL-E and gut microbiome was characterized using shallow shotgun metagenomic DNA sequencing. Results Ten nursing home residents were colonized by ESBL-E, namely Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae species, and were compared to non-carriers. We found that ESBL-E carriers had an alteration in within-sample diversity. Using a bootstrap algorithm, we found that the gut microbiome of ESBL-E carriers was depleted in butyrate-producing species, enriched in succinate-producing species and enriched in pathways involved in intracellular pH homeostasis compared to non-carriers individuals. Several energy metabolism pathways were overrepresented in ESBL-E carriers suggesting a greater ability to metabolize multiple microbiota and mucus layer-derived nutrients. Conclusions The gut microbiome of ESBL-E carriers in nursing homes harbors specific taxonomic and functional characteristics, conferring an environment that enables Enterobacteriaceae expansion. We describe here new functional features associated with ESBL-E carriage that could help us to elucidate the complex interactions leading to colonization persistence in the human gut microbiota.

Long-term gut colonization with ESBL-producingEscherichia coliin participants without known risk factors from the southeastern United States

“…However, pairwise analysis identified multiple taxa with significantly different abundance in carriers and non-carriers. Similar to other studies, we observed enriched taxa belonging to Prevotella (69,70) and depletion of taxa belonging to Sellimonas (71) and Bacteroides uniformis (72). On the other hand, some taxa that other groups found enriched in ESBL-E carriers were identified as depleted in our ESBL-E communities, including Clostridiales (69), Erysipelotrichaceae, Lactococcus, Bilophila and Negativibacillus (70).…”

“…Alpha and beta diversity analysis suggests that ESBL-E carriage was not associated with substantially different gut microbiome composition or diversity, consistent with the results of other studies (68,69).…”

Asymptomatic gut colonization by extended-spectrum beta-lactamase-producing Escherichia coli is not associated with an altered gut microbiome or metabolome in Dutch adults

“…It must be noted that these studies have mostly investigated vulnerable patient populations, such as nursing home residents and hospitalized patients. In such populations it is very complex to disentangle observed differences between colonized and non-colonized individuals from differences due to confounding variables (such as comorbidities and medication) between compared individuals 6,8,[44][45][46] . In our study we excluded individuals based on many microbiome-influencing clinical factors, and performed matching on several clinical variables, as recently recommended for cross-sectional microbiome studies 9 .…”

“…In addition, previous research has generally not focused on species-specific colonization resistance, but rather on a broad category of MDROs (such as ESBL-producing Enterobacterales) 6,8,[44][45][46] . Given the large genomic diversity within species 47 , let alone within the order of Enterobacterales, it is highly unlikely that a common mechanisms exists which could prevent colonization of e.g.…”

“…These conflicting results can, at least partially, be traced back to several confounding factors (e.g. medication) in those studies [5][6][7][8] . It was recently shown that unevenly matched case-controls studies with regard to lifestyle and physiological characteristics can produce spurious microbial associations with human phenotypes like disease, or in this case, colonization by ESBL-producing E. coli 9 .…”