Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
Metabogen, Mölndal, Sweden.
Nature. 2023 Aug;620(7973):381-385. doi: 10.1038/s41586-023-06378-w. Epub 2023 Aug 2.
The human gut microbiota has gained interest as an environmental factor that may contribute to health or disease. 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 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. 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.
人类肠道微生物群已成为一个环境因素，可能有助于健康或疾病。开发下一代益生菌是一种调节肠道微生物群和改善人类健康的有前途的策略；然而，一些关键的候选下一代益生菌是严格的厌氧菌，可能需要与其他细菌协同作用才能最佳生长。普拉梭菌是一种与人类健康相关的高度流行和丰富的人类肠道细菌，但尚未开发成益生菌制剂。在这里，我们描述了普拉梭菌和脱硫弧菌的共分离，脱硫弧菌是一种硫酸盐还原菌，它们可以相互喂养以促进生长和丁酸产生。为了生产下一代益生菌制剂，我们使普拉梭菌适应耐受氧气暴露，并且在概念验证研究中，我们证明共生产物被小鼠和人类耐受（ClinicalTrials.gov 标识符：NCT03728868），并在一部分研究参与者的肠道中检测到。我们的研究描述了一种基于严格厌氧菌适应耐受氧气暴露而不降低潜在有益特性的下一代益生菌生产技术。我们的技术可用于开发其他严格厌氧菌作为下一代益生菌。
