Abstract
Among long-stay critically ill patients in the adult intensive care unit (ICU), there are often marked changes in the complexity of the gut microbiota. However, it remains unclear whether such patients might benefit from enhanced surveillance or from interventions targeting the gut microbiota or the pathogens therein. We therefore undertook a prospective observational study of 24 ICU patients, in which serial faecal samples were subjected to shotgun metagenomic sequencing, phylogenetic profiling and microbial genome analyses. Two-thirds of the patients experienced a marked drop in gut microbial diversity (to an inverse Simpson’s index of <4) at some stage during their stay in the ICU, often accompanied by the absence or loss of potentially beneficial bacteria. Intravenous administration of the broad-spectrum antimicrobial agent meropenem was significantly associated with loss of gut microbial diversity, but the administration of other antibiotics, including piperacillin/tazobactam, failed to trigger statistically detectable changes in microbial diversity. In three-quarters of ICU patients, we documented episodes of gut domination by pathogenic strains, with evidence of cryptic nosocomial transmission of Enterococcus faecium . In some patients, we also saw an increase in the relative abundance of apparent commensal organisms in the gut microbiome, including the archaeal species Methanobrevibacter smithii . In conclusion, we have documented a dramatic absence of microbial diversity and pathogen domination of the gut microbiota in a high proportion of critically ill patients using shotgun metagenomics.
Highlights
Interest has recently focused on the gut microbiota in long-stay patients on the adult intensive care unit (ICU) [1,2,3]
In several patients, we found that an increase in the relative abundance of sequences assigned to a bacterial pathogen (E. coli or E. faecium) occurred in association with an increase in total bacterial biomass and/or an increase in pathogen abundance, confirming that pathogen abundance increased in absolute as well as in relative terms (Fig. S5)
We have shown that surveillance of the gut microbiota in long-stay ICU patients using shotgun metagenomics is capable of detecting episodes of low diversity and pathogen domination, as well as providing genome-level resolution of colonizing pathogens and evidence of cryptic nosocomial transmission
Summary
Interest has recently focused on the gut microbiota in long-stay patients on the adult intensive care unit (ICU) [1,2,3]. Interest has grown in protecting or restoring the integrity of the gut microbiome in ICU patients, using ecological approaches such as probiotics or faecal microbiota transplants [7,8,9,10,11,12,13,14,15,16,17,18]. We undertook a prospective observational study of 24 ICU patients, in which serial faecal samples were subjected to shotgun metagenomic sequencing, phylogenetic profiling and microbial genome analyses, with the aims of evaluating the utility of shotgun metagenomics in long-stay ICU patients, documenting the dynamics of the gut microbiota in this context and determining how it is affected by relevant clinical and demographic factors
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