Complete Genomes of Cultivated Gut Bacteria Reveal Mobile Genetic Element-Driven Functional Diversity with Therapeutic Implications

Wang, H.; Gu, Y.; He, W.; Yang, J.; Liang, H.; Wang, M.; Wu, Z.; Wen, Y.; Wang, J.; Rao, X.; Fan, Y.; Ma, J.; Yang, X.; Tong, X.; Yang, L.; Xu, Y.-s.; Zhao, J.; Zeng, T.; Zhang, Y.; Zhong, Y.; Zhang, H.; Liu, C.; Shen, X.; Kristiansen, K.; Liu, F.; Yang, Z.; Li, W.; Gao, P.; Xu, J.; Li, S.; He, N.; Wang, B.; Jin, X.; Xu, X.; Dong, Y.; Zhou, H.; Zhao, F.; Xiao, L.; Zou, Y.

doi:10.64898/2026.03.25.714112

bioRxiv · 10.64898/2026.03.25.714112

Complete Genomes of Cultivated Gut Bacteria Reveal Mobile Genetic Element-Driven Functional Diversity with Therapeutic Implications

Wang, H.·Gu, Y.·He, W.·Yang, J.·Liang, H.·Wang, M.·Wu, Z.·Wen, Y.·Wang, J.·Rao, X.·Fan, Y.·Ma, J.·Yang, X.·Tong, X.·Yang, L.·Xu, Y.-s.·Zhao, J.·Zeng, T.·Zhang, Y.·Zhong, Y.·Zhang, H.·Liu, C.·Shen, X.·Kristiansen, K.·Liu, F.·Yang, Z.·Li, W.·Gao, P.·Xu, J.·Li, S.·He, N.·Wang, B.·Jin, X.·Xu, X.·Dong, Y.·Zhou, H.·Zhao, F.·Xiao, L.·Zou, Y.

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Abstract

Cultivated bacterial isolates are essential for elucidating gut microbiota functions, yet reliance on fragmented draft genomes and limited mobile genetic element (MGE) annotation has constrained high-resolution analyses. Here, we present the Cultivated Complete Genome Reference (CCGR), a comprehensive compendium of 1,150 fully circularized human gut bacterial genomes. Overcoming draft limitations, CCGR achieves chromosome-scale resolution and reveals distinct evolutionary strategies shaping gene topological organization in response to bacterial growth. Furthermore, we decode the dynamic landscape of MGEs, demonstrating that broad-host-range phages follow strict positional patterns by integrating at conserved chromosomal hotspots flanked by nutrient transporter loci. Importantly, we provide mechanistic in vivo evidence that accessory genomic elements drive strain-level functional heterogeneity. Specifically, the plasmid-encoded scrK gene in Levilactobacillus brevis involved in fructose catabolism is required to mitigate fructose-diet-exacerbated colitis. Collectively, CCGR establishes a framework linking chromosomal architecture and MGEs to bacterial evolution and host health, enabling precise, strain-resolved functional investigations.

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Wang, H., Gu, Y., He, W., Yang, J., Liang, H., Wang, M., Wu, Z., Wen, Y., Wang, J., Rao, X., Fan, Y., Ma, J., Yang, X., Tong, X., Yang, L., Xu, Y.-s., Zhao, J., Zeng, T., Zhang, Y., Zhong, Y., Zhang, H., Liu, C., Shen, X., Kristiansen, K., Liu, F., Yang, Z., Li, W., Gao, P., Xu, J., Li, S., He, N., Wang, B., Jin, X., Xu, X., Dong, Y., Zhou, H., Zhao, F., Xiao, L., Zou, Y.. 2026-03-25. Complete Genomes of Cultivated Gut Bacteria Reveal Mobile Genetic Element-Driven Functional Diversity with Therapeutic Implications. https://doi.org/10.64898/2026.03.25.714112

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