Chen-Liaw A, Aggarwala V, Mogno I, Haifer C, Li Z, Eggers J, Helmus D, Hart A, Wehkamp J, Lamousé-Smith ESN, Kerby RL, Rey FE, Colombel JF, Kamm MA, Olle B, Norman JM, Menon R, Watson AR, Crossett E, Terveer EM, Keller JJ, Borody TJ, Grinspan A, Paramsothy S, Kaakoush NO, Dubinsky MC, and Faith JJ
Despite the fundamental role of bacterial strain variation in gut microbiota function 1-6 , the number of unique strains of a species that can stably colonize the human intestine is still unknown for almost all species. Here we determine the strain richness (SR) of common gut species using thousands of sequenced bacterial isolates with paired metagenomes. We show that SR varies across species, is transferable by faecal microbiota transplantation, and is uniquely low in the gut compared with soil and lake environments. Active therapeutic administration of supraphysiologic numbers of strains per species increases recipient SR, which then converges back to the population average after dosing is ceased. Stratifying engraftment outcomes by high or low SR shows that SR predicts microbial addition or replacement in faecal transplants. Together, these results indicate that properties of the gut ecosystem govern the number of strains of each species colonizing the gut and thereby influence strain addition and replacement in faecal microbiota transplantation and defined live biotherapeutic products., Competing Interests: Competing interests: J.J.F. is a scientific advisory board member and consultant to Vedanta Biosciences, Inc. A.H., J.W., E.S.N.L.-S. are employees of Janssen Research & Development. B.O., J.M.N., R.M., A.R.W. and E.C. are employees of Vedanta Biosciences. J.K. and E.T. received research grants from Vedanta Biosciences. The remaining authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)