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Purpose: There are some challenges to diagnosis in the context of similar diagnostic criteria for late-life depression (LLD) and adult depression due to cognitive impairment and other clinical manifestations. The association between gut microbiota and inflammation remains unclear in LLD. We analyzed gut microbiota characteristics and serum inflammatory cytokines in individuals with LLD to explore the combined role of these two factors in potential biomarkers of LLD. Methods: This was an observational cross-sectional study. Fecal samples and peripheral blood from 29 patients and 33 sex- and age-matched healthy controls (HCs) were collected to detect gut microbiota and 12 inflammatory factors. We analyzed differences in diversity and composition of gut microbiota and evaluated relations among gut microbiota, inflammatory factors, and neuropsychological scales. We extracted potential biomarkers using receiver-operating characteristic curve analysis to predict LLD utilizing the combination of the microbiota and inflammatory cytokines. Results: Elevated systemic inflammatory cytokine levels and gut microbiota dysbiosis were found in LLD patients. Relative abundance of Verrucomicrobia at the phylum level and Megamonas, Citrobacter, and Akkermansia at the genus level among LLD patients was lower than HCs. Abundance of Coprococcus, Lachnobacterium, Oscillospira, and Sutterella was higher in LLD patients. Notably, IL6, IFNγ, Verrucomicrobia, and Akkermansia levels were correlated with depression severity. Our study identified IL6, Akkermansia, and Sutterella as predictors of LLD, and their combination achieved an area under the curve of 0.962 in distinguishing LLD patients from HCs. Conclusion: This research offers evidence of changes within gut microbiota and systemic inflammation in LLD. These findings possibly help elucidate functions of gut microbiota and systemic inflammation in LLD development and offer fresh ideas on biomarkers for clinical practise in the context of LLD. [ABSTRACT FROM AUTHOR]