Christensenella strain resources, genomic/metabolomic profiling, and association with host at species level

ABSTRACT

The gut commensal bacteria Christensenellaceae species are negatively associated with many metabolic diseases, and have been seen as promising next-generation probiotics. However, the cultured Christensenellaceae strain resources were limited, and their beneficial mechanisms for improving metabolic diseases have yet to be explored. In this study, we developed a method that enabled the enrichment and cultivation of Christensenellaceae strains from fecal samples. Using this method, a collection of Christensenellaceae Gut Microbial Biobank (ChrisGMB) was established, composed of 87 strains and genomes that represent 14 species of 8 genera. Seven species were first described and the cultured Christensenellaceae resources have been significantly expanded at species and strain levels. Christensenella strains exerted different abilities in utilization of various complex polysaccharides and other carbon sources, exhibited host-adaptation capabilities such as acid tolerance and bile tolerance, produced a wide range of volatile probiotic metabolites and secondary bile acids. Cohort analyses demonstrated that Christensenellaceae and Christensenella were prevalent in various cohorts and the abundances were significantly reduced in T2D and OB cohorts. At species level, Christensenellaceae showed different changes among healthy and disease cohorts. C. faecalis, F. tenuis, L. tenuis, and Guo. tenuis significantly reduced in all the metabolic disease cohorts. The relative abundances of C. minuta, C. hongkongensis and C. massiliensis showed no significant change in NAFLD and ACVD. and C. tenuis and C. acetigenes showed no significant change in ACVD, and Q. tenuis and Geh. tenuis showed no significant change in NAFLD, when compared with the HC cohort. So far as we know, this is the largest collection of cultured resource and first exploration of Christensenellaceae prevalences and abundances at species level.

KEYWORDS:

• Christensenellaceae
• ChrisGMB biobank, metabolite profiling
• genetic and phenotypic diversity
• cultivation
• associations with health and diseases at species level

Acknowledgments

We thank NMDC (China National Microbiology Data Center) team for the data preservation, ChrisGMB homepage construction and maintenance. We would like to thank Zhifeng Li, Jing Zhu, Jingyao Qu and Guannan Lin from the Core Facilities for Life and Environmental Sciences, State Key laboratory of Microbial Technology of Shandong University for technical guidance. We would like to thank Xiaoju Li and Haiyan Sui from Shandong University Core Facilities for Life and Environmental Sciences for their help with the TEM.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

XWS finished the experiment and the first draft of the manuscript. XWS, HJH and YLW worked on genome analysis. XMW, HJH, RQW, HYN, HYC, ML, and FLL participated in strains isolation, cultivation and characterization. RA worked on the nomination of new taxa.

XWS, XMW, and HJ worked the deposit of cultured strains. CL supervised on experimental methodology and data analysis, SJL concepted and supervised the research, and finalized the manuscript.

Consent for publication

All authors read and agree to the publication of this manuscript.

Data availability statement

The datasets generated and analyzed in this study are available as the following: Basically, all the descriptive information and data related to 87 ChrisGMB strains were available at the hGMB homepage (https://hgmb.nmdc.cn/subject/christensenellaceae). The16S rRNA gene sequences of the 87 strains were deposited in China National Microbiology Data Center (NMDC) and the accession numbers were listed in supplementary Table S5. All assembled genomes obtained in this study were available at NMDC under Project NMDC10018522 (https://nmdc.cn/resource/genomics/project/detail/).

Ethics approval and consent to participate

This study was approved by the Ethics Committee of the School of Basic Medical Sciences, Shandong University (ECSBMSSDU2023-1-59).

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2024.2347725

Additional information

Funding

This work was supported financially by the National Key Research and Development Program of China (No. 2019YFA0905600; No. 2022YFA1304100)