Synergy and oxygen adaptation for development of next-generation probiotics

Muhammad Tanweer Khan, Chinmay Dwibedi, Daniel Sundh, Meenakshi Pradhan, Jamie D. Kraft, Robert Caesar, Valentina Tremaroli, Mattias Lorentzon and Fredrik Bäckhed ()
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Muhammad Tanweer Khan: University of Gothenburg
Chinmay Dwibedi: University of Gothenburg
Daniel Sundh: University of Gothenburg
Meenakshi Pradhan: University of Gothenburg
Jamie D. Kraft: University of Gothenburg
Robert Caesar: University of Gothenburg
Valentina Tremaroli: University of Gothenburg
Mattias Lorentzon: University of Gothenburg
Fredrik Bäckhed: University of Gothenburg

Nature, 2023, vol. 620, issue 7973, 381-385

Abstract: Abstract The human gut microbiota has gained interest as an environmental factor that may contribute to health or disease1. 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 anaerobic2 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 formulations2. 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.

Date: 2023
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DOI: 10.1038/s41586-023-06378-w

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