This study aimed to investigate alterations in the gut microbiota of patients with depression compared to those in the gut microbiota of healthy individuals based on enterotypes as a classification framework. Fecal bacteria FASTA/Q samples from 333 Chinese participants, including 107 healthy individuals (Healthy group) and 226 individuals suffering from depression (DP group), were analyzed. The participants were classified into three enterotypes: Bacteroidaceae (ET-B), Lachnospiraceae (ET-L), and Prevotellaceae (ET-P). An α-diversity analysis revealed no significant differences in microbial diversity between the Healthy and DP groups across all enterotypes. However, there were substantial differences in the gut microbial composition for β-diversity, particularly within ET-L and ET-B. The DP group within ET-B exhibited a higher abundance of Proteobacteria, while a linear discriminant analysis (LDA) of the DP group showed an increased relative abundance of specific genera, such as Mediterraneibacter, Blautia, Bifidobacterium, and Clostridium. Within ET-L, Bifidobacterium, Blautia, Clostridium, Collinsella, and Corynebacterium were significantly higher in the DP group in the LDA and ANOVA-like differential expression-2 (ALDEx2) analyses. At the species level of ET-L, Blautia luti, Blautia provencensis, Blautia glucerasea, Clostridium innocuum, Clostridium porci, and Clostridium leptum were the primary bacteria in the DP group identified using the machine learning approach. A network analysis revealed a more tightly interconnected microbial community within ET-L than within ET-B. This suggests a potentially stronger functional relationship among the gut microbiota in ET-L. The metabolic pathways related to glucose metabolism, tryptophan and tyrosine metabolism, neurotransmitter metabolism, and immune-related functions showed strong negative associations with depression, particularly within ET-L. These findings provide insights into the gut-brain axis and its role in the pathogenesis of depression, thus contributing to our understanding of the underlying mechanisms in Asian individuals. Further research is warranted to explain the mechanistic links between gut microbiota and depression and to explore their potential for use in precision medicine interventions.
Keywords: enterotype; glucose metabolism; gut microbiota; gut–brain axis; network analysis.