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 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%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.

The human gut microbiome in critical illness: disruptions, consequences, and therapeutic frontiers

“…[ 56 ] An abnormal gut microbiome composition has been linked to delirium and septic encephalopathy; notably, a resolution of delirium was documented in a patient diagnosed with C. difficile infection post fecal microbiota transplantation (FMT). [ 57 – 60 ] Such microbial imbalances have also been correlated with mild cognitive impairments, dementia, and the behavioral manifestations of depression, schizophrenia, and addiction. [ 61 ]…”

Increased IgA-mediated responses to the gut paracellular pathway and blood–brain barrier proteins predict delirium due to hip fracture in older adults

“…Although previous studies have associated post-surgery delirium with BBB breakdown ( 18 ), there is no direct evidence that the breakdown of the paracellular pathway is associated with delirium. Nevertheless, there is some data on associations between gut microbiota diversities and postoperative delirium ( 19 , 20 ). Few studies supported the hypothesis of an association between insomnia and abnormalities in the gut-brain axis ( 21 , 22 ).…”