Meta-analysis of the microbial diversity cultured in bioreactors simulating the gut microbiome: another key to unlocking the microbial dark matter

Background

The challenges surrounding the mechanistic study of the gut ecosystem have motivated the development and use of multiple in vitro models, such as microbial cultures and bioreactors, that simulate some of the features of the gut environment. The control technology,  integrated into bioreactors, allowing tuning of pH, redox potential, and retention time, has allowed the recovery and isolation of microorganisms that are hard to culture with conventional methods opening access to hitherto unexplored microbial species - microbial “dark matter”. Although multiple bioreactor platforms have been developed, there is a lack of studies describing and comparing the microbial diversity cultivated in these devices. This study aimed to characterise and compare the microbial diversity of 1,619 samples from 19 studies in which various in vitro models were used to cultivate faecal microbiota. 

Results

The community structure differed between the 19 studies based on β-diversity analysis using t-SNE and the Hellinger distance, with inter-individual variation between the faecal inoculum donors contributing the most influence. Moreover, there was no overlap between samples from studies that used the same bioreactor model. Studies with more than one donor showed higher variations than those with pooled samples. 

The diversity profiles of the samples within each study based on α-diversity (Hill numbers) were not dependent on the complexity of the bioreactors. Nevertheless, further analyses of the samples of five studies showed Amplicon Sequence Variants enrichment in the bioreactors compared to the faecal inoculum, two of which provided a mucosal component. Finally, a comparative analysis of the taxonomy at family level in the 19 studies versus those listed in the Data Repository for Human Gut Microbiota (GMRepo) revealed 30 families that were unique to bioreactor models. This finding highlights the potential of bioreactors to uncover a hidden diversity, which is not detected with culture-independent methods.

Conclusions:

This study shows that bioreactors can sustain stable communities and recover the most abundant taxa from faecal samples. Additionally, we highlight the potential of bioreactors as a tool to enrich species that are difficult to cultivate, allowing insights into their role in host-microbiome interactions.