A synthetic microbial consortium protects against obesity by regulating vitamin B6 metabolism

ABSTRACT

Constructing synthetic microbial consortia is a challenging task but holds enormous potential for various applications. Our previous droplet-based microfluidic approach allowed for the isolation of bacteria that could utilize metabolites from an engineered bacterium BsS-RS06551 with anti-obesity potential, facilitating the construction of synthetic microbial consortia. Here, we identified a strain of Bifidobacterium pseudocatenulatum JJ3 that interacted with BsS-RS06551, and in vitro coculture showed that BsS-RS06551 was likely to interact with JJ3 through five dipeptides. Pathway analysis revealed that the vitamin B6 metabolism pathway was enriched in the coculture of BsS-RS06551 and JJ3 compared with the individual culture of BsS-RS06551. Additionally, we confirmed that the administration of JJ3 significantly alleviated obesity and related disorders in mice fed a high-fat diet. Notably, continuous ingestion of the synthetic microbial consortium comprising BsS-RS06551 and JJ3 not only exhibited a more pronounced impact on alleviating obesity compared to the individual administration of BsS-RS06551 or JJ3 but also enriched the population of Bifidobacterium longum and perturbed the vitamin B6 metabolism pathway in the gut. Synthetic microbial consortia represent a promising frontier for synthetic biology, and our strategy provides guidance for constructing and applying such consortia.

KEYWORDS:

• Synthetic microbial consortia
• obesity
• gut microbiota
• metabolomics
• microbial interaction
• engineered probiotics

Acknowledgments

We are very grateful for Shanghai Biotree Biotech Co. Ltd for technical support at untargeted metabolomics services. We thank Scidraw and Servier Medical Art. The mice model element in Figure 8 were sourced from Scidraw.io. Parts of the Figures 1 and 8 were drawn by using pictures from Servier Medical Art. Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License.

Disclosure statement

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

Authors’ contributions

GK, HH, GQ, YW, LW, CX and MG designed the experiment. GK, HH, XC and MG planned and performed experiments. XC, LW and MG carried out data analysis. GK, HH, XC, LW and MG wrote the main manuscript text and prepared figures S1–8. XC, LW and MG wrote prepared figures S1-S8 and table S1. All authors reviewed the manuscript.

Availability of data and material

The 16S rRNA gene sequencing raw data generated in this study have been deposited in the NCBI under accession No. PRJNA967479. The raw data of non-targeted metabolomics reported in this study have been deposited in the ScienceDB database (https://www.scidb.cn/anonymous/cTJZanF1).

Ethics approval and consent to participate

All animal experiments were conducted in accordance with the guidelines set forth by the Animal Ethical and Welfare Committee (AEWC) and approved by Tianjin University (Approval No. TJUE-2023-167), ensuring the ethical and humane treatment of laboratory animals.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2024.2304901

Additional information

Funding

The present study was supported by grants from the National Key Research and Development Project (Grant No. 2019YFA0905600), the Science and Technology Program of Tianjin, China (Grant No. 22YFZCSN00090), and the China-CEEC Joint Education Project (Grant No. 2022196).