Microecological modulation of Faecalibacterium spp.: Prebiotic-mediated cross-feeding networks.
As a paradigmatic next-generation probiotic, Faecalibacterium species play a major role in butyrate generation, intestinal barrier integrity, and immune homeostasis. However, its clinical translation is severely hindered by profound physiological fragility-namely, extreme oxygen sensitivity and inherent metabolic bottlenecks, such as its strict dependence on exogenous acetate for butyrate synthesis-which collectively impede in vitro cultivation, in vivo colonisation, and scalable production. To circumvent these constraints, leveraging the gut microbiota's "cross-feeding" network has emerged as a highly promising ecological strategy, with prebiotics serving as precise molecular tools to orchestrate these interactions. This review systematically delineates the biological characteristics and metabolic constraints of Faecalibacterium, comprehensively dissecting its cross-feeding mechanisms with pivotal commensals (e.g., Bifidobacterium and Akkermansia muciniphila) across metabolic complementarity, ecological niche synergy, and multi-species networks. Building on this ecological framework, we highlight how traditional prebiotics (oligosaccharides and polysaccharides) and novel non-conventional substrates (e.g., riboflavin and specific glycoconjugates) can be strategically utilised to drive these networks for the targeted enrichment of Faecalibacterium. Bridging ecological interventions with formulation engineering, this paper further critically evaluates advanced delivery technologies designed to safeguard live cell viability. Emphasis is placed on dual-modality protection strategies: physical spatial isolation (via microencapsulation and cryoprotectant optimisation) and biochemical microenvironmental remodelling (via antioxidant excipients). Ultimately, by integrating microecological interaction theory with cutting-edge formulation engineering, this review provides a comprehensive roadmap for the rational design, development, and industrial-scale production of Faecalibacterium-based biotherapeutics, functional foods, and medical nutrition.