Background: Human gut microbiota is now well appreciated for its association with various diseases and physiological states. Key species presence in early life plays a significant role in determining the compositional signature of the microbiome, a phenomenon known as the priority effect. However, the principle that governs species selection based on the primary colonizer is not yet clear, and very little is known about the key species in early-life gut microbiota that contribute to this assembly. In this study, we perform a high throughput screening of mucosal adhesion using a culture library collection to find out possible species involved in this assembly. Using strong mucin adhering species, we further investigate the gut microbiome assembly using a continuous-flow bioreactor system in vitro.
Method: Biofilm formation by the human gut microbiome library was assessed using a crystal violet screening assay. Confocal laser scanning microscopy and scanning electron microscopy were utilized to visualize the structure and viability of biofilms formed on mucin-coated surfaces. A packed column and drip flow Bioreactor were utilized to mimic the mucosal gut environment for exploring biofilm dynamics and microbial recruitment. The microbial composition was determined through metagenomic analysis.
Results: Among 102 gut microbial species from a healthy human population, we could identify strong mucin adherers, including Bifidobacterium longum, Bacteroides caccae, B. finegoldi, Olsenella umbonate. Our bioreactor results demonstrated that early microbial colonization is depended on mucin, as a very minimum number of bacteria were able to adhere, and their adherence remained consistent even within a community. Notably, our metagenome analysis revealed that specific strong mucin utilizers bifidobacterium longum show no detection of pathogenic bacteria recruitment, underscoring the effectiveness of the mucosal barrier and the early colonizers in preventing pathogenic invasion. Additionally, by examining pediatric gut microbiome data and mucosal data across various health conditions, we sought to correlate early microbial configuration with potential health outcomes.
Conclusion: Our findings indicate that initial colonizers significantly shape the subsequent microbial community structure by influence the mucosal environment. This study advances our understanding of gut microbiome assembly and its implications for health by demonstrating that the initial microbial colonizers, through priority effects, set the stage for subsequent community development.