The role of the microbiota in the management of intensive care patients

Abstract

The composition of the gut microbiota is highly dynamic and changes according to various conditions. The gut microbiota mainly includes difficult-to-cultivate anaerobic bacteria, hence knowledge about its composition has significantly arisen from culture-independent methods based on next-generation sequencing (NGS) such as 16S profiling and shotgun metagenomics. The gut microbiota of patients hospitalized in intensive care units (ICU) undergoes many alterations because of critical illness, antibiotics, and other ICU-specific medications. It is then characterized by lower richness and diversity, and dominated by opportunistic pathogens such as Clostridioides difficile and multidrug-resistant bacteria. These alterations are associated with an increased risk of infectious complications or death. Specifically, at the time of writing, it appears possible to identify distinct microbiota patterns associated with severity or infectivity in COVID-19 patients, paving the way for the potential use of dysbiosis markers to predict patient outcomes. Correcting the microbiota disturbances to avoid their consequences is now possible. Fecal microbiota transplantation is recommended in recurrent C. difficile infections and microbiota-protecting treatments such as antibiotic inactivators are currently being developed. The growing interest in the microbiota and microbiota-associated therapies suggests that the control of the dysbiosis could be a key factor in the management of critically ill patients. The present narrative review aims to provide a synthetic overview of microbiota, from healthy individuals to critically ill patients. After an introduction to the different techniques used for studying the microbiota, we review the determinants involved in the alteration of the microbiota in ICU patients and the latter's consequences. Last, we assess the means to prevent or correct microbiota alteration.

Keywords: C. difficile; Dysbiosis; Fecal microbiota transplantation; Intensive care; Microbiota; Multidrug-resistant bacteria; Probiotics.

Fig. 1

The Sanger sequencing method and next-generation sequencing steps. Sanger sequencing relies on dye-labeled nucleotides that are added to an elongating DNA strand thus determining each base according to the color of the dye. One of the NGS technique allows the specific amplification of an isolated DNA fragment by slide fixation such as in the Illumina chemistry, which is based on-chip amplification in bridge connection that allows simultaneous identification of DNA bases which emit a unique fluorescence signal when they are incorporated into the nucleic acid chain. PCR: polymerase chain reaction. NGS: next-generation sequencing

Fig. 2

Schematic representation of classically used next-generation sequencing methods. 16S rRNA coding gene amplification and shotgun metagenomics are well-used techniques for microbiota studies. OTU: operational taxonomic unit (an OTU being assumed to be a bacterial genus).NGS: next-generation sequencing

Fig. 3

Schematic representation of bacterial richness and diversity concepts. In the figure, each color represents a different bacterial taxon. Richness and diversity can be considered at different levels of taxa, from phylum to species. Richness represents the variety of bacterial communities observed in a specific ecosystem and is greater with the number of different bacterial species found in it. Diversity is related to the preponderance of bacterial communities one over the others, in the ecosystem: when a bacterial taxon is overrepresented in the niche, microbial diversity decrease. Various indices are used to estimate the bacterial diversity. Shannon index estimates the bacterial diversity and increases with the number of different species in an ecosystem. Simpson index increases with the probability that two random species within an ecosystem are the same and is therefore higher when one or more bacterial species are preponderant in an ecosystem. The figure includes material available from Servier Medical Art (https://smart.servier.com) under a Creative Commons license

Fig. 4

Main microbiota variations in ICU patients and available means to restore dysbiosis. In healthy subjects, microbiota presents important interpersonal variations, but is always composed by four major phyla and one of its important roles is resistance to colonization by exogenous bacteria. In ICU, many factors (rust color) alter the microbiota integrity with numerous consequences. In the right part of the figure, are illustrated the classically described treatments (bold and black letters) playing a role on the microbiota and compensating or preventing alterations. The fecal microbiota transplantation is the most popular microbiota-associated treatment, but other solutions aiming at preserving or restoring the integrity of the microbiota continue to be investigated. MDRO multidrug-resistant organism, ICU intensive care unit, rCDI recurrent Clostridioides difficile infection. The figure includes material available from Servier Medical Art (https://smart.servier.com) under a Creative Commons license