GLP-1-gut microbiotal axis and enteral feeding intolerance in critically ill neurological patients

Autonomic dysfunction following central nervous system injury predisposes critically ill neurological patients to enteral feeding intolerance (FI), but the underlying gut microbiota-glucagon-like peptide-1 (GLP-1) mechanisms remain unclear.

We conducted a prospective cohort study of 60 patients in the intensive care unit receiving enteral nutrition (EN), with fecal and blood sample collection at admission (Q stage) and at the FI onset or EN cessation (H stage). The gut microbiota was analyzed via 16S rRNA sequencing, and GLP-1 and blood glucose were measured. Alpha and beta diversity, taxonomic composition, and correlations with GLP-1/glucose were evaluated.

At the Q stage, the tolerant group exhibited higher alpha diversity (ACE, Chao indices) and enrichment of Blautia, while intolerant patients showed early dysbiosis. At the H stage, beta diversity differed significantly (ANOSIM: R = 0.2, P = 0.01), with decreased Bacteroidetes and increased Enterococcus in intolerant patients. Spearman analysis revealed progressive strengthening of gut microbiotal correlations with GLP-1 and blood glucose, establishing a "gut microbiota-GLP-1-blood glucose" regulatory axis.

Stage-dependent gut microbiotal changes predict the FI risk and correlate with GLP-1-mediated glucose and motility regulation. Early alpha diversity and specific taxa (e.g., Bilophila) may serve as predictive biomarkers. Targeting the gut microbiota and GLP-1 pathways represents a promising therapeutic strategy to improve EN tolerance in critically ill neurological patients.