TL;DR
Recent evidence is discussed across Escherichia coli, Citrobacter rodentium, Klebsiella spp.
Enterococcus faecalis is a human gut commensal and major opportunistic pathogen that is frequently found within polymicrobial communities at biofilm-associated infection sites, including the catheterized urinary tract, surgical and chronic wounds, the gut, and oral and mucosal niches. Its interactions with co-isolated bacteria and fungi can alter biofilm formation, antimicrobial susceptibility, immune signaling, and disease severity, yet the molecular basis of these interactions, and whether the same mechanisms recur across anatomically distinct sites, remains incompletely understood. In this review, we explore mechanistic studies of E. faecalis polymicrobial biology, organized around recurring interaction types. We first describe microbial mechanisms such as metabolic cross-feeding and iron-restricted physiology, notably ornithine/arginine exchange, lactate, and heme, as well as quorum sensing and interspecies signaling through the Fsr system, and cross-kingdom interactions with Candida albicans, emphasizing motifs that recur across different infections. We then examine host-coupled dynamics, in which the host participates mechanistically through nutritional immunity, tissue injury, immune modulation, and feedback loops that reshape the community. Throughout this review, we highlight how defined, host-relevant synthetic communities can facilitate mechanistic determinants for clinical co-occurrence, and we outline some of the limitations of current models while proposing priorities for further research.
Enterohemorrhagic Escherichia coli (EHEC) is a major foodborne pathogen that causes hemorrhagic colitis and hemolytic uremic syndrome. Increasing evidence indicates that the gut microbiota plays a central role in modulating EHEC pathogenesis through complex metabolic and signaling networks. Beneficial commensals, including Bifidobacterium, Lactobacillus, and segmented filamentous bacteria, contribute to colonization resistance by competing for nutrients and adhesion sites, producing antimicrobial metabolites, and enhancing epithelial barrier integrity. In contrast, certain species such as Bacteroides thetaiotaomicron and Enterococcus faecalis may promote EHEC virulence by altering intestinal nutrient availability or triggering the expression of virulence genes. Microbiota-derived metabolites, including short-chain fatty acids, succinate, indole, riboflavin, nicotinamide, ethanolamine, and L-malate, act as important regulatory signals that connect microbial metabolism with LEE-mediated virulence pathways. Understanding these host-microbe-pathogen interactions provides a mechanistic basis for developing microbiota-targeted interventions such as probiotics, prebiotics, and fecal microbiota transplantation that enhance colonization resistance and attenuate virulence. Integration of AI-based analytics with multi-omics approaches is expected to facilitate the design of personalized, mechanism-driven therapeutic strategies for the control of EHEC infection.
Salmonella enterica serovar Typhimurium (STm) is a leading cause of diarrheal disease and efficiently colonizes the gut lumen despite microbiota-mediated colonization resistance. Emerging evidence indicates that STm does not simply evade or overcome these barriers, but instead exploits host immune responses and microbiota-derived metabolic activities to create a permissive intestinal niche. In this review, we discuss recent advances in our understanding of STm gut colonization, with a focus on how host antimicrobial factors and microbiota-derived metabolites are repurposed to promote pathogen growth, motility, and invasion. We highlight findings showing that the antimicrobial lectin RegIIIβ, together with microbiota-dependent metabolites such as fatty acid-derived cues and polyamines, can unexpectedly facilitate STm colonization. Together, these studies support a model in which host defense programs and microbial metabolism are redirected to promote pathogen fitness, revealing potential therapeutic opportunities for controlling enteric infections.
BACKGROUND Bacteroides fragilis is a dominant member of the human intestinal microbiota and is known for its ecological plasticity and capacity to persist under fluctuating intestinal conditions. Bile salts are abundant host-derived molecules that act not only as antimicrobial agents but also as environmental cues shaping bacterial adaptation in the gut. OBJECTIVES This study investigated how B. fragilis adapts to bile salts at physiological, structural, and metabolic levels. METHODS A panel of clinical and commensal strains was evaluated for bile tolerance. The B. fragilis type strain ATCC 25285 was selected for in-depth analyses of biofilm formation, extracellular matrix composition, antimicrobial tolerance, and mucin translocation. RESULTS Clinical isolates showed high bile tolerance, with MIC values up to 14% (w/v). Bile exposure promoted biofilm formation, particularly in the presence of glucose and mucin-derived carbohydrates, resulting in thick, protein-rich extracellular matrices. Biofilms formed under bile conditions displayed increased tolerance to Metronidazole and the antimicrobial peptide LL-37. Bile salts also significantly reduced bacterial translocation across a mucin layer. CONCLUSIONS Our results support a multilayered adaptive model in which bile salts act as environmental cues that reshape B. fragilis physiology, enhancing fitness, persistence, and host interactions while favoring luminal colonization.
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.
