The mammalian gastrointestinal tract is a stage for dynamic inter-kingdom interactions among bacteria, fungi, viruses, and protozoa, which collectively shape the gut micro-ecology and influence host physiology. Despite being a modest fraction, the fungal community, also referred to as mycobiota, represents a critical component of the gut microbiota. Emerging evidence suggests that fungi act as early colonizers of the intestine, exerting a lasting influence on gut development. Meanwhile, the composition of the mycobiota is influenced by multiple factors, with diet, nutrition, drug use (e.g., antimicrobials), and physical condition standing as primary drivers. During its establishment, the mycobiota forms both antagonistic and synergistic relationships with bacterial communities within the host. For instance, intestinal fungi can inhibit bacterial colonization by producing alcohol, while certain bacterial pathogens exploit fungal iron carriers to enhance their growth. However, the regulatory mechanisms governing these complex interactions remain poorly understood. In this review, we first introduce the methodologies for studying the microbiota, then address the significance of the mycobiota in the mammalian intestine, especially during weaning when all ‘primary drivers’ change, and, finally, discuss interactions between fungi and bacteria under various influencing factors. Our review aims to shed light on the complex inter-kingdom dynamics between fungi and bacteria in gut homeostasis and provide insights into how they can be better understood and managed to improve host health and disease outcomes.

Background: The use of antibiotics in swine production during the stressful weaning period is widespread. While their impact on the gut microbiome is documented, their effect on the developing oral microbiota, a critical gateway to systemic health, remains poorly understood. This study investigated how chronic exposure to tylosin (TYL) or a chlortetracycline-sulfadiazine-penicillin combination (CSP) shapes oral microbiota assembly in piglets from 21 to 60 days of age. Results: Healthy piglets exhibited a defined ecological succession, transitioning from an early, Pseudomonadota-dominated types of oral microbiota, or referred to as orotypes (driven by Moraxellaceae) at weaning to a stable, mature Bacillota-dominated state (driven by Lachnospiraceae) by 40 days of age. Antibiotic exposure disrupted this developmental program. CSP treatment locked the microbiota in an immature, Pseudomonadota-dominated state, while TYL promoted a dispersed and unstable Bacillota community. Dysbiosis was marked by enrichment of pathobionts (e.g., Moraxella , Bergeyella ) and depletion of beneficial commensals like Veillonella and Phocaeicola , with the latter reduced in both the oral and gut microbiota. These structural shifts were linked to dysregulated microbial energy and lipid metabolism. Crucially, antibiotics compromised mucosal immunity, reducing salivary secretory IgA (SIgA), and provoked inflammation, evidenced by elevated salivary extracellular ATP (eATP), histological damage and transcriptome alteration in oral tissue, and changed serum metabolites. Conclusions: Our findings demonstrate that early-life antibiotic exposure disrupts the developmental programming of the oral ecosystem. The oral microbiota serves as a sensitive indicator of antibiotic impact and a key mediator of systemic health, highlighting the need for strategies that safeguard microbial succession to promote sustainable swine health.