||Proteoglycan (PG) extracted from salmon nasal cartilage has potential to be a prophylactic agent. Daily oral administration of the PG attenuates systemic inflammatory response in the experimental mouse models. In this study, we applied the culture-independent approach to investigate an alteration of intestinal microbiota composition in PG-administered mice. The results indicated a greater diversity of the intestinal microbiota in the PG-administered mice in comparison with control. Population level of clostridia increased in the small intestine and decreased in the large intestine upon PG administration. These phylotypes were included saccharolytic and butyrate-producing bacteria those are able to utilize and ferment saccharides. In contrast, the proportion of an asaccharolytic proteobacterium decreased in both small and large intestine. Importantly, population level of probiotic lactobacilli and bacteria exhibiting the immunomodulatory effect increased in the PG-administered mice. In addition, several disease-associated bacteria decreased upon PG administration. These results provided the understanding in the specific role of PG involved in host immune modulation and supported our hypothesis that daily oral administration of PG controls the overall balance in composition of the intestinal microbial community.