Synergy and oxygen adaptation for development of next-generation probiotics

Nature. 2023 Aug;620(7973):381-385. doi: 10.1038/s41586-023-06378-w. Epub 2023 Aug 2.

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.

MeSH terms

  • Aerobiosis
  • Animals
  • Biotechnology* / methods
  • Butyrates / metabolism
  • Faecalibacterium prausnitzii / drug effects
  • Faecalibacterium prausnitzii / metabolism
  • Gastrointestinal Microbiome*
  • Humans
  • Mice
  • Oxygen / metabolism
  • Oxygen / pharmacology
  • Probiotics* / metabolism
  • Symbiosis

Substances

  • Butyrates
  • Oxygen

Supplementary concepts

  • Desulfovibrio piger

Associated data

  • ClinicalTrials.gov/NCT03728868