Selective utilization of medicinal polysaccharides by human gut Bacteroides and Parabacteroides species

Zepeng Qu, Hongbin Liu, Ji Yang, Linggang Zheng, Jumin Huang, Ziming Wang, Chun Xie, Wenlong Zuo, Xiong Xia, Lin Sun, Yifa Zhou, Ying Xie, Jingguang Lu, Yizhun Zhu, Lili Yu, Lihua Liu, Hua Zhou (), Lei Dai () and Elaine Lai-Han Leung ()
Additional contact information
Zepeng Qu: Taipa
Hongbin Liu: Chinese Academy of Sciences
Ji Yang: Guangdong Pharmaceutical University
Linggang Zheng: Taipa
Jumin Huang: Macau
Ziming Wang: Macau
Chun Xie: Macau
Wenlong Zuo: Chinese Academy of Sciences
Xiong Xia: Chinese Academy of Sciences
Lin Sun: Northeast Normal University
Yifa Zhou: Northeast Normal University
Ying Xie: Guangzhou
Jingguang Lu: Taipa
Yizhun Zhu: Taipa
Lili Yu: Taipa
Lihua Liu: Yanbian University
Hua Zhou: Guangzhou
Lei Dai: Chinese Academy of Sciences
Elaine Lai-Han Leung: Macau

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract Human gut Bacteroides and Parabacteroides species play crucial roles in human health and are known for their capacity to utilize diverse polysaccharides. Understanding how these bacteria utilize medicinal polysaccharides is foundational for developing polysaccharides-based prebiotics and drugs. Here, we systematically mapped the utilization profiles of 20 different medicinal polysaccharides by 28 human gut Bacteroides and Parabacteroides species. The growth profiles exhibited substantial variation across different bacterial species and medicinal polysaccharides. Ginseng polysaccharides promoted the growth of multiple Bacteroides and Parabacteroides species; in contrast, Dendrobium polysaccharides selectively promoted the growth of Bacteroides uniformis. This distinct utilization profile was associated with genomic variation in carbohydrate-active enzymes, rather than monosaccharides composition variation among medicinal polysaccharides. Through comparative transcriptomics and genetical manipulation, we validated that the polysaccharide utilization locus PUL34_Bu enabled Bacteroides uniformis to utilize Dendrobium polysaccharides (i.e. glucomannan). In addition, we found that the GH26 enzyme in PUL34_Bu allowed Bacteroides uniformis to utilize multiple plant-derived mannan. Overall, our results revealed the selective utilization of medicinal polysaccharide by Bacteroides and Parabacteroides species and provided insights into the use of polysaccharides in engineering the human gut microbiome.

Date: 2025
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DOI: 10.1038/s41467-025-55845-7

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