AUTHOR=Crost Emmanuelle H. , Le Gall Gwenaelle , Laverde-Gomez Jenny A. , Mukhopadhya Indrani , Flint Harry J. , Juge Nathalie 

TITLE=Mechanistic Insights Into the Cross-Feeding of Ruminococcus gnavus and Ruminococcus bromii on Host and Dietary Carbohydrates

JOURNAL=Frontiers in Microbiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.02558

DOI=10.3389/fmicb.2018.02558

ISSN=1664-302X

ABSTRACT=<p>Dietary and host glycans shape the composition of the human gut microbiota with keystone carbohydrate-degrading species playing a critical role in maintaining the structure and function of gut microbial communities. Here, we focused on two major human gut symbionts, the mucin-degrader <italic>Ruminococcus gnavus</italic> ATCC 29149, and <italic>R. bromii</italic> L2-63, a keystone species for the degradation of resistant starch (RS) in human colon. Using anaerobic individual and co-cultures of <italic>R. bromii</italic> and <italic>R. gnavus</italic> grown on mucin or starch as sole carbon source, we showed that starch degradation by <italic>R. bromii</italic> supported the growth of <italic>R. gnavus</italic> whereas <italic>R. bromii</italic> did not benefit from mucin degradation by <italic>R. gnavus</italic>. Further we analyzed the growth (quantitative PCR), metabolite production (<sup>1</sup>H NMR analysis), and bacterial transcriptional response (RNA-Seq) of <italic>R. bromii</italic> cultured with RS or soluble starch (SS) in the presence or absence of <italic>R. gnavus</italic>. In co-culture fermentations on starch, <sup>1</sup>H NMR analysis showed that <italic>R. gnavus</italic> benefits from transient glucose and malto-oligosaccharides released by <italic>R. bromii</italic> upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products. Differential expression analysis (DESeq 2) on starch (SS and RS) showed that the presence of <italic>R. bromii</italic> induced changes in <italic>R. gnavus</italic> transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase, in line with the ability of <italic>R. gnavus</italic> to utilize <italic>R. bromii</italic> starch degradation products. In the RS co-culture, <italic>R. bromii</italic> showed a significant increase in the induction of tryptophan (Trp) biosynthesis genes and a decrease of vitamin B12 (VitB12)-dependent methionine biosynthesis as compared to the mono-culture, suggesting that Trp and VitB12 availability become limited in the presence of <italic>R. gnavus</italic>. Together this study showed a direct competition between <italic>R. bromii</italic> and <italic>R. gnavus</italic> on RS, suggesting that <italic>in vivo</italic>, the <italic>R. gnavus</italic> population inhabiting the mucus niche may be modulated by the supply of non-digestible carbohydrates reaching the colon such as RS.</p>