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. 2022 Aug 29;11(17):2621.
doi: 10.3390/foods11172621.

Lactococcus garvieae FUA009, a Novel Intestinal Bacterium Capable of Producing the Bioactive Metabolite Urolithin A from Ellagic Acid

Haoyu Mi  1   2 , Shu Liu  1   2   3 , Yang Hai  4 , Guang Yang  1   2   3 , Jing Lu  1   2   3 , Fuxiang He  1   2 , Yaling Zhao  1   2 , Mengjie Xia  1   2 , Xiaoyue Hou  1   2   3   5   6 , Yaowei Fang  1   2   5
Affiliations

Lactococcus garvieae FUA009, a Novel Intestinal Bacterium Capable of Producing the Bioactive Metabolite Urolithin A from Ellagic Acid

Haoyu Mi et al. Foods. .

Abstract

Dietary polyphenol ellagic acid has anti-cancer and anti-inflammatory activities, and these biological activities require the conversion of ellagic acid to urolithins by intestinal microbes. However, few gut microbes are capable of metabolizing ellagic acid to produce urolithins, limiting the beneficial effects of ellagic acid on health. Here, we describe an intestinal bacterium Lactococcus garvieae FUA009 isolated from the feces of a healthy volunteer. It was demonstrated via HPLC and UPLC-MS analysis that the end product of ellagic acid metabolism of FUA009 was urolithin A. In addition, we also examined the whole genome sequence of FUA009 and then assessed the safety and probiotic properties of FUA009 based on a complete genome and phenotype analysis. We indicated that FUA009 was safe, which was confirmed by FUA009 being sensitive to multiple antibiotics, having no hemolytic activity, and being free of aggressive putative virulence factors. Moreover, 19 stress-responsive protein genes and 8 adhesion-related genes were predicted in the FUA009 genome. Furthermore, we demonstrated that FUA009 was tolerant to acid and bile salt by determining the cell viability in a stress environment. In summary, Lactococcus garvieae FUA009, as a novel UA-producing bacterium, not only contributes to the study of the metabolic pathway of ellagic acid but is also expected to be a novel probiotic candidate.

Keywords: Lactococcus garvieae; complete genome; ellagic acid; plant-derived activities; safety and probiotic characteristics; urolithin A.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Lactococcus garvieae FUA009 could be capable of producing UA from ellagic acid. (A) HPLC analysis at 305 nm of the seven urolithin standards. (B) HPLC analysis at 305 nm of the fermentation broth of FUA009 at 36 h. (C) HPLC analysis at 305 nm of the fermentation broth of FUA009 at 48 h. (D) UPLC-MS analysis at 305 nm of the UA standard. (E) UPLC-MS analysis at 305 nm of the fermentation product of FUA009 at 48 h. Note: Uro-A—urolithin A, Uro-B—urolithin B, Uro-C—urolithin C, Uro-D—urolithin D, Uro-E—urolithin E, Uro-M6—urolithin-M6, EA—ellagic acid, isoUro-A—isourolithin A.
Figure 2
Figure 2
FUA009 was assigned to the species Lactococcus garvieae. (A) Phylogenetic tree showing the relationships between the Lactococcus garvieae FUA009 and other representatives of the family Lactococcus. The tree was constructed by using the neighbor-joining method based on 16S rRNA gene sequences. The distance matrix was calculated using the Jukes and Cantor method. Bar: 1% nucleotide sequence difference. Numbers at nodes (≥70%) indicate support for internal branches within the tree obtained using bootstrap analysis (percentages of 500 re-samplings). (B) The species annotation results of Lactococcus garvieae FUA009 in the Non-Redundant Protein Database.
Figure 3
Figure 3
Lactococcus garvieae FUA009 did not show any hemolysis ability on the blood agar plates.
Figure 4
Figure 4
Tolerance of Lactococcus garvieae FUA009 in vitro at different pHs (A) and concentrations of bile salts (B).
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