Abstract

Flavonoids are a common component of the human diet with widely reported health-promoting properties. The gut microbiota transforms these compounds affecting the overall metabolic outcome of flavonoid consumption. Flavonoid-degrading bacteria are often studied in pure and mixed cultures but the multiple interactions between quercetin-degraders and the rest of the community have been overlooked. In this study, a comparative metataxonomic analysis of fecal communities supplemented with the flavonoid quercetin led us to identify a potential competitive exclusion interaction between two sequence variants related to the flavonoid-degrading species, Flavonifractor plautii, that belong to the same genus but different species. During incubation of fecal slurries with quercetin, the relative abundance of these two variants was inversely correlated; one variant, ASV_65f4, increased in relative abundance in half of the libraries and the other variant, ASV_a45d, in the other half. This pattern was also observed with 6 additional fecal samples that were transplanted into germ-free mice fed two different diets. Mouse’s diet did not change the pattern of dominance of either variant, and initial relative abundances did not predict which one ended up dominating. Potential distinct metabolic capabilities of these two Flavonifractor-related species were evidenced, as only one variant, ASV_65f4, became consistently enriched in complex communities supplemented with acetate but without quercetin. Genomic comparison analysis of the close relatives of each variant revealed that ASV_65f4 may be an efficient utilizer of ethanolamine which is formed from the phospholipid phosphatidylethanolamine that is abundant in the gut and feces. Other discordant features between ASV_65f4- and ASV_a45d-related groups may be the presence of flagellar and galactose-utilization genes, respectively. Overall, we showed that the Flavonifractor genus harbors variants that present a pattern of negative co-occurrence and that may have different metabolic and morphological traits, whether these differences affect the dynamic of quercetin degradation warrants further investigation.

Highlights

  • Flavonoids are 3-ring phenolic compounds produced by the secondary metabolism of plants

  • The well-recognized quercetin-degraders, F. plautii and Eubacterium ramulus, are butyrate-producers, a short-chain fatty acid that is the preferred source of energy of colonocytes and essential for colon health [8]

  • As a result of this phylogenetic analysis, we identified Amplicon Sequence Variants (ASVs) that were 100% identical to F. plautii (ASV_65f4) and E. ramulus (ASV_c588) (S5 Table)

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Summary

Introduction

Flavonoids are 3-ring phenolic compounds produced by the secondary metabolism of plants. They are found in fruits and vegetables and their regular consumption is associated with health benefits [1,2]. Quercetin is one of the most abundant in the human diet It exerts effects on the immune, digestive, endocrine, nervous, and cardiovascular systems [3]. It is not clear to what extent do the health effects of flavonoids depend on their transformation to biologically active compounds by the gut microbiota. Vissiennon and collaborators showed that the anxiolytic activity of quercetin is induced by DOPAC and not by the parent compound, evidencing a case in which the microbial metabolite exerts the beneficial effect [5]. The well-recognized quercetin-degraders, F. plautii (formerly Clostridium orbiscindens) and Eubacterium ramulus, are butyrate-producers, a short-chain fatty acid that is the preferred source of energy of colonocytes and essential for colon health [8]

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