Network analysis detected microbial co-occurrence patterns and identified keystone species in the gut microbial community of mice in response to stress and chondroitin sulfate disaccharide dietary supplement

Authors: LIU, FANG - Ocean University Of China; LI, ZHAOJIE - Ocean University Of China; WANG, ZIONG - Ocean University Of China; XUE, CHANG-HU - Ocean University Of China; TANG, QING-JUAN - Ocean University Of China; Li, Robert

Submitted to: International Journal of Molecular Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/26/2019
Publication Date: 4/30/2019
Citation: Liu, F., Li, Z., Wang, Z., Xue, C., Tang, Q., Li, R.W. 2019. Network analysis detected microbial co-occurrence patterns and identified keystone species in the gut microbial community of mice in response to stress and chondroitin sulfate disaccharide dietary supplement. International Journal of Molecular Sciences. 20(9):2130. https://doi.org/10.3390/ijms20092130
DOI: https://doi.org/10.3390/ijms20092130

Interpretive Summary: Chondroitin sulfate (CS) possesses various biological functions by acting as a signaling molecule. For example, CS is involved in parasite recognition while CS type E displays potent antiviral activities. One of the CS precursors, glycosamine, has been widely used as a dietary supplement. In this study, we investigated microbial interactions and identified key microbial taxa that were strongly correlated with several physiological parameters in response to dietary intervention with CS component disaccharides under both healthy and stressed conditions using co-occurrence network tools, indicating that CS attains bioactivity by repressing intestinal inflammation and by promoting gut homeostasis under stress. The results also suggest that altered network topologies, especially the node connectivity in some key modules, may have important functional implications for tissue and blood physiological parameters. The results will interest microbiologists, physiologists, community ecologists, and veterinarians interested in microbial interactions in the gut and may facilitate future progress in microbial community engineering.

Technical Abstract: Microbial co-occurrence patterns were inferred using a random matrix theory (RMT) based approach in the gut microbiome of mice in response to chondroitin sulfate component disaccharide (CSD) dietary treatments under healthy and stressed conditions in this study. CSD restored the blood urea nitrogen (BUN) level to normality from a level significantly elevated in the mice under stress (P <0.05). While oversize size and structure of the global networks, which possessed a high modularity ranging from 0.8 to 0.9, were similar, the network composition was distinctly different between different experimental conditions. The exercise stress significantly disrupted the network composition and microbial co-occurrence patterns. 34 Operational Taxonomic Units (OTU) were identified as module hubs and connectors, likely acting as generalists in the microbial community. An OTU belonging to Mucispirillum schaedleri acted as a connector in the stressed network restored by CSD supplement and may play a key role for bridging intimate interactions between the host and its microbiome. The correlation detected several modules with strong correlations with physiological parameters. For example, Modules M02 (under stress) and S5 (under stress but supplemented with CSD) were strongly correlated with BUN (P < 0.05; r = 0.90 and - 0.75, respectively). The Mantel test unraveled a positive correlation between node connectivity of the OTU assigned to Proteobacteria with superoxide dismutase activities (r = 0.57, P <0.05) under stress, providing further evidence that Proteobacteria can be developed as a pathological marker. Moreover, the results suggest that altered network topologies, especially the node connectivity in some key modules, may have important functional implications on tissue and blood physiological parameters. Our findings provided novel insights into microbial interactions in gut microbial communities of the mice in response to stress and CSD supplement and may facilitate future endeavor in microbial community engineering.