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Background: The gut-lung axis, pivotal for respiratory health, is inadequately explored in pulmonary and critical care medicine (PCCM) inpatients. Methods: Examining PCCM inpatients from three medical university-affiliated hospitals, we conducted 16S ribosomal RNA sequencing on stool samples (inpatients, n = 374; healthy controls, n = 105). We conducted statistical analyses to examine the gut microbiota composition in PCCM inpatients, comparing it to that of healthy controls. Additionally, we explored the associations between gut microbiota composition and various clinical factors, including age, white blood cell count, neutrophil count, platelet count, albumin level, hemoglobin level, length of hospital stay, and medical costs. Results: PCCM inpatients exhibited lower gut microbiota diversity than healthy controls. Principal Coordinates Analysis revealed marked overall microbiota structure differences. Four enterotypes, including the exclusive Enterococcaceae enterotype in inpatients, were identified. Although no distinctions were found at the phylum level, 15 bacterial families exhibited varying abundances. Specifically, the inpatient population from PCCM showed a significantly higher abundance of Enterococcaceae, Lactobacillaceae, Erysipelatoclostridiaceae, Clostridiaceae, and Tannerellaceae. Using random forest analyses, we calculated the areas under the receiver operating characteristic curves (AUCs) to be 0.75 (95% CIs 0.69–0.80) for distinguishing healthy individuals from inpatients. The four most abundant genera retained in the classifier were Blautia, Subdoligranulum, Enterococcus, and Klebsiella. Conclusions: Evidence of gut microbiota dysbiosis in PCCM inpatients underscores the gut-lung axis's significance, promising further avenues in respiratory health research. [ABSTRACT FROM AUTHOR]