Rapid gastrointestinal loss of Clostridial Clusters IV and XIVa in the ICU associates with an expansion of gut pathogens

Abstract

Commensal gastrointestinal bacteria resist the expansion of pathogens and are lost during critical illness, facilitating pathogen colonization and infection. We performed a prospective, ICU-based study to determine risk factors for loss of gut colonization resistance during the initial period of critical illness. Rectal swabs were taken from adult ICU patients within 4 hours of admission and 72 hours later, and analyzed using 16S rRNA gene sequencing and selective culture for vancomycin-resistant Enterococcus (VRE). Microbiome data was visualized using principal coordinate analyses (PCoA) and assessed using a linear discriminant analysis algorithm and logistic regression modeling. 93 ICU patients were analyzed. At 72 hours following ICU admission, there was a significant decrease in the proportion of Clostridial Clusters IV/XIVa, taxa that produce short chain fatty acids (SCFAs). At the same time, there was a significant expansion in Enterococcus. Decreases in Cluster IV/XIVa Clostridia were associated with loss of gut microbiome colonization resistance (reduced diversity and community stability over time). In multivariable analysis, both decreased Cluster IV/XIVa Clostridia and increased Enterococcus after 72 hours were associated with receipt of antibiotics. Cluster IV/XIVa Clostridia, although a small fraction of the overall gastrointestinal microbiome, drove distinct clustering on PCoA. During initial treatment for critical illness, there was a loss of Cluster IV/XIVa Clostridia within the distal gut microbiome which associated with an expansion of VRE and with a loss of gut microbiome colonization resistance. Receipt of broad-spectrum antibiotics was associated with these changes.

Relationship Between Dietary Fiber Intake and Short‐Chain Fatty Acid–Producing Bacteria During Critical Illness: A Prospective Cohort Study

“…The primary outcome was the relative abundance of SCFA‐producing bacteria after 72 hours in the ICU based on 16S ribosomal RNA (rRNA) gene sequencing results from the 72‐hour rectal swab. This was defined as the sum total of the relative abundance of the following taxa within clostridial clusters IV/XIVa, with all taxa specified at the lowest possible hierarchical level: Faecalibacterium prausnitzii , Eubacterium rectale , Ruminococcus , Blautia, Coprococcus , and Roseburia . Additional sequencing details are described in the supplementary methods.…”

“…This was a retrospective study with prospective collection of biosamples. 8 In brief, adults ࣙ 18 years old were eligible for the study if they were newly admitted to any one of the 5 distinct medical or surgical ICUs and could reach within 4 hours of ICU admission. Rectal swabs were performed at the time of ICU admission and 72 hours later (±4 hours), and clinical data were gathered.…”

“…Dietary fiber is a prebiotic that increases the abundance of bacteria producing butyrate and other short‐chain fatty acids (SCFAs). These bacteria, or their metabolites, appear to have immunomodulatory benefits that are relevant for ICU patients . In bone marrow transplant recipients and selective ICU cohorts, increased abundance of SCFA‐producing bacteria was associated with decreased MDR organism colonization, including decreased vancomycin‐resistant Enterococcus (VRE) .…”

“…These bacteria, or their metabolites, appear to have immunomodulatory benefits that are relevant for ICU patients . In bone marrow transplant recipients and selective ICU cohorts, increased abundance of SCFA‐producing bacteria was associated with decreased MDR organism colonization, including decreased vancomycin‐resistant Enterococcus (VRE) . In the ICU, diminished levels of SCFA producers have been associated with higher Enterococcus and risk for death .…”

“…[7][8][9] In bone marrow transplant recipients and selective ICU cohorts, increased abundance of SCFAproducing bacteria was associated with decreased MDR organism colonization, including decreased vancomycinresistant Enterococcus (VRE). 8,10 In the ICU, diminished levels of SCFA producers have been associated with higher Enterococcus and risk for death. 11 In healthy volunteers and ambulatory patients, fiber is well tolerated and increases SCFA producer levels.…”