Abstract
The human gut microbiota has gained interest as an environmental factor that may contribute to health or disease 1. The development of next-generation probiotics is a promising strategy to modulate the gut microbiota and improve human health; however, several key candidate next-generation probiotics are strictly anaerobic 2 and may require synergy with other bacteria for optimal growth. Faecalibacterium prausnitzii is a highly prevalent and abundant human gut bacterium associated with human health, but it has not yet been developed into probiotic formulations 2. Here we describe the co-isolation of F. prausnitzii and Desulfovibrio piger, a sulfate-reducing bacterium, and their cross-feeding for growth and butyrate production. To produce a next-generation probiotic formulation, we adapted F. prausnitzii to tolerate oxygen exposure, and, in proof-of-concept studies, we demonstrate that the symbiotic product is tolerated by mice and humans (ClinicalTrials.gov identifier: NCT03728868) and is detected in the human gut in a subset of study participants. Our study describes a technology for the production of next-generation probiotics based on the adaptation of strictly anaerobic bacteria to tolerate oxygen exposures without a reduction in potential beneficial properties. Our technology may be used for the development of other strictly anaerobic strains as next-generation probiotics.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Nature |
| Vol/bind | 620 |
| Sider (fra-til) | 381-385 |
| ISSN | 0028-0836 |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:M.T.K. is employed in part by Metabogen AB and F.B. is founder of Metabogen AB. Metabogen AB has contributed with economic support and product for the human intervention, but was not involved in analyses of the data. F.B. receives research funding from Biogaia AB and is on the scientific advisory board of Bactolife A/S. The other authors declare no competing interests.
Funding Information:
The authors thank A. Hallén, R. Jakubowicz, L. Olsson, M. Bergentall and S. Håkansson for technical assistance; and H. Imberg for sharing the SAS macro for the Fisher–Pitman permutation test and confidence interval. Computations were enabled by resources in projects SNIC 2020/5-384 and SNIC 2019/8-169 provided by the Swedish National Infrastructure for Computing (SNIC) at UPPMAX, partially funded by the Swedish Research Council through grant agreement no. 2018-05973. This study was in part supported by Knut and Alice Wallenberg Foundation (2017.0026), the Swedish Research Council (2019-01599), Transatlantic Networks of Excellence Award from the Leducq Foundation (17CVD01), AFA insurances, Swedish Heart Lung Foundation (20210366), the Novo Nordisk foundation (NNF17OC0028232), grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALFGBG- 718101) and by Metabogen AB. F.B. is Wallenberg Scholar and Torsten Söderberg Professor in Medicine.
Publisher Copyright:
© 2023, The Author(s).