Dataset Information

A Novel Streptococcus thermophilus FUA329 Isolated from Human Breast Milk Capable of Producing Urolithin A from Ellagic Acid.

ABSTRACT: Urolithin A, a metabolite of ellagic acid, has many beneficial biological activities for people. Strains capable of producing urolithin A from ellagic acid have the hope of becoming the next-generation probiotics. However, only a few species of these strains have been reported. In this study, FUA329, a strain capable of converting ellagic acid to urolithin A in vitro, was isolated from the breast milk of healthy Chinese women. The results of morphological observation, physiological and biochemical tests, and 16S rRNA gene sequence analysis confirmed that the strain FUA329 was Streptococcus thermophilus. In addition, the S. thermophilus FUA329 growth phase is consistent with the degradation of ellagic acid, and urolithin A was produced in the stationary phase, with a maximum concentration of 7.38 μM at 50 h. The corresponding conversion efficiency of urolithin A from ellagic acid was 82%. In summary, S. thermophilus FUA329, a novel urolithin A-producing bacterium, would be useful for the industrial production of urolithin A and may be developed as a next-generation probiotic.

SUBMITTER: Liu Q

PROVIDER: S-EPMC9601659 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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A Novel <i>Streptococcus thermophilus</i> FUA329 Isolated from Human Breast Milk Capable of Producing Urolithin A from Ellagic Acid.

Liu Qitong Q Liu Shu S Ye Qinwen Q Hou Xiaoyue X Yang Guang G Lu Jing J Hai Yang Y Shen Juan J Fang Yaowei Y

Foods (Basel, Switzerland) 20221020 20

Urolithin A, a metabolite of ellagic acid, has many beneficial biological activities for people. Strains capable of producing urolithin A from ellagic acid have the hope of becoming the next-generation probiotics. However, only a few species of these strains have been reported. In this study, FUA329, a strain capable of converting ellagic acid to urolithin A in vitro, was isolated from the breast milk of healthy Chinese women. The results of morphological observation, physiological and biochemic ...[more]

PMID: 37431038

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Project description:Urolithins are intestinal microbial metabolites produced from ellagitannin- and ellagic acid-containing foods such as walnuts, strawberries, and pomegranates. These metabolites, better absorbed than their precursors, can contribute significantly to the beneficial properties attributed to the polyphenols ellagitannins and ellagic acid (EA). However, both the ability of producing the final metabolites in this catabolism (urolithins A, B and isourolithin A) and the health benefits associated with ellagitannin consumption differ considerably among individuals depending on their gut microbiota composition. Three human urolithin metabotypes have been previously described, i.e., metabotype 0 (urolithin non-producers), metabotype A (production of urolithin A as unique final urolithin) and metabotype B (urolithin B and/or isourolithin A are produced besides urolithin A). Although production of some intermediary urolithins has been recently attributed to intestinal species from Eggerthellaceae family named Gordonibacter urolithinfaciens and Gordonibacter pamelaeae, the identification of the microorganisms responsible for the complete transformation of EA into the final urolithins, especially those related to metabotype B, are still unknown. In the present research we illustrate the isolation of urolithin-producing strains from human feces of a healthy adult and their ability to transform EA into different urolithin metabolites, including isourolithin A. The isolates belong to a new genus from Eggerthellaceae family. EA transformation and urolithin production arisen during the stationary phase of the growth of the bacteria under anaerobic conditions. The HPLC-DAD-MS analyses demonstrated the sequential appearance of 3,8,9,10-tetrahydroxy-urolithin (urolithin M6), 3,8,9-trihydroxy-urolithin (urolithin C) and 3,9-dihydroxy-urolithin (isourolithin A) while 3,8-dihydroxy-urolithin (urolithin A) and 3-hydroxy-urolithin (urolithin B) were not detected. For the first time isourolithin A production capacity of pure strains has been described. The biological activity attributed to urolithins A and B and isourolithin A (anti-inflammatory, anti-carcinogenic, cardioprotective, and neuroprotective properties) explains the relevance of identifying these urolithin-producing bacteria as potential novel probiotics with applications in the development of functional foods and nutraceuticals. Their human administration could improve the health benefits upon ellagitannin consumption, especially in metabotype 0 individuals. However, further research is necessary to probe well-established beneficial effects on the host and safety requirements before being considered among the next-generation probiotics.

Project description:Streptococcus thermophilus plays important roles in the dairy industry and is widely used as a dairy starter in the production of fermented dairy products. The genomes of S. thermophilus strains CS5, CS9, CS18, and CS20 from fermented milk in China were sequenced and used for biodiversity analysis. In the present study, the phylogenetic analysis of all 34 S. thermophilus genomes publicly available including these four strains reveals that the phylogenetic reconstruction does not match geographic distribution as strains isolated from the same continent are not even clustered on the nearby branches. The core and variable genes were also identified, which vary among strains from 0 to 202. CS9 strain contained 127 unique genes from a variety of distantly related species. It was speculated that CS9 had undergone horizontal gene transfer (HGT) during the long evolutionary process. The safety evaluation of these four strains indicated that none of them contains antibiotic resistance genes and that they are all sensitive to multiple antibiotics. In addition, the strains do not contain any pathogenic virulence factors or plasmids and thus can be considered safe. Furthermore, these strains were investigated in terms of their technological properties including milk acidification, exopolysaccharide (EPS) and γ-aminobutyric acid (GABA) production, and in vitro survival capacity in the gastrointestinal tract. CS9 possesses a special eps gene cluster containing significant traces of HGT, while the eps gene clusters of CS5, CS18, and CS20 are almost the same. The monosaccharide compositional analysis indicated that crude EPS-CS5, EPS-CS9, EPS-CS18, and EPS-CS20 contain similar monosaccharide compositions with different ratios. Furthermore, CS9 was one of a few GABA-producing strains that could ferment glutamate to produce GABA, which is beneficial for improving the acid tolerance of the strain. CS18 has the most potential for the production of fermented food among these four strains because of its fast growth rate, rapid acidifying capacity, and stronger acid and bile salt resistance capacity. This study focused on the genome analysis of the four new S. thermophilus strains to investigate the diversity of strains and provides a reference for selecting excellent strains by use of the genome data.

Project description:Numerous studies signify that diets rich in phytochemicals offer many beneficial functions specifically during pathologic conditions, yet their effects are often not uniform due to inter-individual variation. The host indigenous gut microbiota and their modifications of dietary phytochemicals have emerged as factors that greatly influence the efficacy of phytoceutical-based intervention. Here, we investigated the biological activities of one such active microbial metabolite, Urolithin A (UA or 3,8-dihydroxybenzo[c]chromen-6-one), which is derived from the ellagic acid (EA). Our study demonstrates that UA potently inhibits heme peroxidases i.e. myeloperoxidase (MPO) and lactoperoxidase (LPO) when compared to the parent compound EA. In addition, chrome azurol S (CAS) assay suggests that EA, but not UA, is capable of binding to Fe3+, due to its catechol-like structure, although its modest heme peroxidase inhibitory activity is abrogated upon Fe3+-binding. Interestingly, UA-mediated MPO and LPO inhibition can be prevented by innate immune protein human NGAL or its murine ortholog lipocalin 2 (Lcn2), implying the complex nature of host innate immunity-microbiota interactions. Spectral analysis indicates that UA inhibits heme peroxidase-catalyzed reaction by reverting the peroxidase back to its inactive native state. In support of these in vitro results, UA significantly reduced phorbol myristate acetate (PMA)-induced superoxide generation in neutrophils, however, EA failed to block the superoxide generation. Treatment with UA significantly reduced PMA-induced mouse ear edema and MPO activity compared to EA treated mice. Collectively, our results demonstrate that microbiota-mediated conversion of EA to UA is advantageous to both host and microbiota i.e. UA-mediated inhibition of pro-oxidant enzymes reduce tissue inflammation, mitigate non-specific killing of gut bacteria, and abrogate iron-binding property of EA, thus providing a competitive edge to the microbiota in acquiring limiting nutrient iron and thrive in the gut.

Dataset Information

A Novel Streptococcus thermophilus FUA329 Isolated from Human Breast Milk Capable of Producing Urolithin A from Ellagic Acid.

Publications

A Novel <i>Streptococcus thermophilus</i> FUA329 Isolated from Human Breast Milk Capable of Producing Urolithin A from Ellagic Acid.

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