Whereas the composition of the human gut microbiome is well resolved, predictive understanding is still lacking. Here, we followed a bottom-up strategy to explore human gut community dynamics: we established a synthetic community composed of three representative human gut isolates (Roseburia intestinalis L1-82, Faecalibacterium prausnitzii A2-165 and Blautia hydrogenotrophica S5a33) and explored their interactions under well-controlled conditions in vitro. Systematic mono- and pair-wise fermentation experiments confirmed competition for fructose and cross-feeding of formate. We quantified with a mechanistic model how well tri-culture dynamics was predicted from mono-culture data. With the model as reference, we demonstrated that strains grown in co-culture behaved differently than in mono-culture and confirmed their altered behavior at the transcriptional level. In addition, we showed with replicate tri-cultures and simulations that dominance in tri-culture sensitively depended on initial conditions. Our work has important implications for gut microbial community modeling as well as ecological interaction detection from batch cultures.
RNA-seq results have been deposited to the Short Read Archive under the study identifier SRP136465 (https://www.ncbi.nlm.nih.gov/sra/SRP136465). Fermentation data have been submitted to Dryad (doi:10.5061/dryad.g83f29f). Source data has been provided for Figures 3 to 6.
Data from: Integrated culturing, modeling and transcriptomics uncovers emergent behavior in a synthetic gut communityAvailable at Dryad Digital Repository under a CC0 Public Domain Dedication.
- Kevin D'hoe
- Kevin D'hoe
- Karoline Faust
- Frédéric Moens
- Verónica Lloréns-Rico
- Stefan Vet
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Xochitl Morgan, University of Otago, New Zealand
© 2018, D'hoe et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
MicroRNAs (miR), as important epigenetic control factors, reportedly regulate wound repair. However, our insufficient knowledge of clinically relevant miRs hinders their potential therapeutic use. For this, we performed paired small and long RNA-sequencing and integrative omics analysis in human tissue samples, including matched skin and acute wounds collected at each healing stage and chronic nonhealing venous ulcers (VUs). On the basis of the findings, we developed a compendium (https://www.xulandenlab.com/humanwounds-mirna-mrna), which will be an open, comprehensive resource to broadly aid wound healing research. With this first clinical, wound-centric resource of miRs and mRNAs, we identified 17 pathologically relevant miRs that exhibited abnormal VU expression and displayed their targets enriched explicitly in the VU gene signature. Intermeshing regulatory networks controlled by these miRs revealed their high cooperativity in contributing to chronic wound pathology characterized by persistent inflammation and proliferative phase initiation failure. Furthermore, we demonstrated that miR-34a, miR-424, and miR-516, upregulated in VU, cooperatively suppressed keratinocyte migration and growth while promoting inflammatory response. By combining miR expression patterns with their specific target gene expression context, we identified miRs highly relevant to VU pathology. Our study opens the possibility of developing innovative wound treatment that targets pathologically relevant cooperating miRs to attain higher therapeutic efficacy and specificity.