Association Between Gut Microbiota and Delirium in Acutely Ill Older Adults

Abstract

Our aim was to investigate the association between gut microbiota and delirium occurrence in acutely ill older adults. We included 133 participants 65+ years consecutively admitted to the emergency department of a tertiary university hospital, between September 2019 and March 2020. We excluded candidates with ≥24-hour antibiotic utilization on admission, recent prebiotic or probiotic utilization, artificial nutrition, acute gastrointestinal disorders, severe traumatic brain injury, recent hospitalization, institutionalization, expected discharge ≤48 hours, or admission for end-of-life care. A trained research team followed a standardized interview protocol to collect sociodemographic, clinical, and laboratory data on admission and throughout the hospital stay. Our exposure measures were gut microbiota alpha and beta diversities, taxa relative abundance, and core microbiome. Our primary outcome was delirium, assessed twice daily using the Confusion Assessment Method. Delirium was detected in 38 participants (29%). We analyzed 257 swab samples. After adjusting for potential confounders, we observed that a greater alpha diversity (higher abundance and richness of microorganisms) was associated with a lower risk of delirium, as measured by the Shannon (odds ratio [OR] = 0.77; 95% confidence interval [CI] = 0.60-0.99; p = .042) and Pielou indexes (OR = 0.69; 95% CI = 0.51-0.87; p = .005). Bacterial taxa associated with pro-inflammatory pathways (Enterobacteriaceae) and modulation of relevant neurotransmitters (Serratia: dopamine; Bacteroides, Parabacteroides: GABA) were more common in participants with delirium. Gut microbiota diversity and composition were significantly different in acutely ill hospitalized older adults who experienced delirium. Our work is an original proof-of-concept investigation that lays a foundation for future biomarker studies and potential therapeutic targets for delirium prevention and treatment.

Keywords: Consciousness disorders; Hospitalization; Microbiome.

Figure 1.

Inclusion flowchart of study participants.

Figure 2.

Alpha diversity by delirium-related outcomes in the overall swab sample. We represented Shannon and Pielou indexes of our primary analysis as follows: (A) Delirium occurrence; (B) Delirium severity by the Confusion Assessment Method-Severity (CAM-S); (C) Level of consciousness by the Richmond Agitation and Sedation Scale (RASS). Data were analyzed using non-adjusted generalized estimating equations and presented as medians (interquartile ranges). Lower Shannon and Pielou indexes indicate poorer bacterial diversity and evenness. *p < .05.

Figure 3.

Graphical representation of beta diversity and relative abundances in the overall swab sample according to delirium occurrence. (A) Principal coordinates analysis (PCoA) plot; each point in the graph represents a different sample. Blue dots represent swabs from non-delirium participants and red dots represent those from delirium participants. Beta diversity (Bray-Curtis distance) was numerically compared across groups using PERMANOVA. Results from the homogeneity of multivariable variances (PERMDISP) analyses showed that the observed differences were not alternatively explained by excessive data dispersion. (B) Relative abundances across groups at the genus level. (C) Linear discriminant analysis (LDA) for comparison of bacterial features across groups.

Figure 4.

Change in microbiota composition of swab samples from participants with early CAM conversion (incident delirium or delirium resolution). Samples were collected from the same individuals with and without delirium at different time points. For samples of participants with delirium, the core microbiota was uniquely represented by the genera Bacteroides, Parabacteroides, Methanobrevibacter, and Varibaculum. CAM, Confusion Assessment Method.