Gut microbiota is the collection of microbes that lives in the host. Glycan is the major factor to shape the composition of microbial community. Nostoc sphaeroids Kütz (NSK) has been used as food and medicine for thousands of years in Asian countries while the bioactivity on gut microbiota is unclear till now. Here, we used NSK polysaccharide and NSK powder to investigate the bioactivity on the gut microbiota of C57BL/6j mice, respectively. By 16S ribosomal RNA gene sequencing, we found the composition of gut microbiota had been changed and differed from each other. However, the abundance of Bacteroides, Parabacteroides, Escherichia-Shigella and Parasutterella on genus level were significantly increased by NSK polysaccharide and NSK powder. In addition, Akkermansia and Rikenellaceae were enriched by NSK powder. Moreover, we found the IL-1β and IL-6 decreased significantly while TNF-α and IL-10 increased significantly especially in NSK powder group. Intriguingly, the increased microbes were significantly positively co-related with TNF-α and IL-10 while negatively co-related with IL-1β and IL-6 by co-relation and network analysis. The above results suggested that Nostoc sphaeroids Kütz may selectively enrich a “core bacterial community” and add new evidence to discover how Nostoc sphaeroids Kütz has biological function.Copyright © 2020. Published by Elsevier B.V.