Targeted prebiotic application of gluconic acid-containing oligosaccharides promotes Faecalibacterium growth through microbial cross-feeding networks.

The gut microbiome plays a crucial role in human health, and certain bacterial species, such as Faecalibacterium prausnitzii, are particularly beneficial. This study conducted a comprehensive investigation of prebiotic compounds that showed potential for specifically promoting beneficial gut bacteria. Using in vitro fecal cultures and a human intervention study, we identified maltobionic acid and lactobionic acid as compounds that specifically promoted Faecalibacterium growth both in vitro and in vivo without significantly affecting Bifidobacterium, which is typically increased by traditional prebiotics. In a human intervention study (n = 27), a significant increase was observed in Faecalibacterium abundance following maltobionic acid supplementation, with effectiveness correlating with the initial Parabacteroides abundance. Mechanistic investigations revealed a cross-feeding pathway between gut bacteria. In this pathway, Parabacteroides species converted the gluconic acid moiety of maltobionic and lactobionic acids to glucuronic acid, which was then preferentially utilized by Faecalibacterium. These findings suggest that gluconic acid-containing oligosaccharides are promising prebiotics for the targeted enhancement of beneficial Faecalibacterium and underscore the importance of microbial interactions in prebiotic research, offering new avenues for personalized microbiome modulation strategies.