Association of gut microbiota and inflammatory markers with enteral nutrition intolerance in patients with early-stage moderate-to-severe intracerebral hemorrhage

ABSTRACT Enteral nutrition intolerance (ENI) is a common and challenging complication in patients with moderate-to-severe intracerebral hemorrhage (msICH). Emerging evidence suggests that gut microbiota is vital for host immune regulation and nutrient metabolism. However, the relationship between intestinal microbial alterations, inflammatory responses, and ENI in patients with early-stage msICH (emsICH) remains poorly understood. Therefore, this study aimed to explore these associations. A total of 100 patients with emsICH were enrolled in this study, including 50 with ENI and 50 without ENI (NENI). The gut microbiota composition was assessed using 16S ribosomal RNA gene sequencing, and the relationships between microbial profiles, systemic inflammatory indicators, and ENI status were systematically analyzed. Patients with ENI exhibited significantly reduced alpha diversity and distinct microbial structure when compared to those with NENI. Linear discriminant analysis effect size identified 19 differentially abundant taxa, with pathogenic genera, including Enterococcus and Finegoldia , enriched in patients with ENI. However, beneficial short-chain fatty acid-producing genera, such as Subdoligranulum and Faecalibacterium , were enriched in patients with NENI. A six-genus biomarker panel demonstrated a strong predictive power for ENI (area under the curve = 0.812). Functional phenotype analysis revealed an increased abundance of Gram-negative and facultative anaerobic bacteria in patients with ENI. Moreover, ENI-associated genera were positively correlated with blood inflammatory indicators, whereas NENI-associated taxa exhibited negative correlations. The analysis of the Kyoto Encyclopedia of Genes and Genomes pathways suggested that several essential physiological pathways in ENI were disturbed, with upregulation of inflammation-related signaling pathways (e.g., Jak-STAT and MAPK) and downregulation of pathways involved in metabolism (particularly in energy metabolism). Gut microbiota dysbiosis in patients with emsICH is strongly associated with ENI and systemic inflammation. Specific microbial signatures may serve as non-invasive biomarkers for ENI risk assessment. These findings shed light on gut microbiota-associated inflammation and the ENI axis and offer a theoretical basis for microbiota-targeted and nutritional interventions in neurocritical care. IMPORTANCE Enteral nutrition intolerance (ENI) is a frequent and serious complication in patients with moderate-to-severe intracerebral hemorrhage (ICH). Our study demonstrates that ENI is strongly associated with gut microbiota imbalance, characterized by an overrepresentation of inflammation-promoting bacteria and a loss of beneficial short-chain fatty acid-producing taxa. This microbial shift was closely linked to heightened systemic inflammation, providing new insights into the gut-inflammation-ENI axis in neurocritical illness. By identifying specific bacterial signatures, our findings suggest that stool-based microbial assessment may serve as a noninvasive tool for early risk prediction and highlight the potential of microbiota-targeted strategies to improve nutritional management and outcomes in patients with ICH.