Bioavailability of dietary polyphenols and gut microbiota metabolism: Antimicrobial properties

Polyphenolic compounds are plant nutraceuticals showing a huge structural diversity, including chlorogenic acids, hydrolyzable tannins, and flavonoids (flavonols, flavanones, flavan-3-ols, anthocyanidins, isoflavones, and flavones). Most of them occur as glycosylated derivatives in plants and foods. In order to become bioactive at human body, these polyphenols must undergo diverse intestinal transformations, due to the action of digestive enzymes, but also by the action of microbiota metabolism. After elimination of sugar tailoring (generating the corresponding aglycons) and diverse hydroxyl moieties, as well as further backbone reorganizations, the final absorbed compounds enter the portal vein circulation towards liver (where other enzymatic transformations take place) and from there to other organs, including behind the digestive tract or via blood towards urine excretion. During this transit along diverse tissues and organs, they are able to carry out strong antiviral, antibacterial, and antiparasitic activities. This paper revises and discusses these antimicrobial activities of dietary polyphenols and their relevance for human health, shedding light on the importance of polyphenols structure recognition by specific enzymes produced by intestinal microbial taxa

Bioavailability of Dietary Polyphenols and Gut Microbiota Metabolism: Antimicrobial Properties

Polyphenolic compounds are plant nutraceuticals showing a huge structural diversity, including chlorogenic acids, hydrolyzable tannins, and flavonoids (flavonols, flavanones, flavan-3-ols, anthocyanidins, isoflavones, and flavones). Most of them occur as glycosylated derivatives in plants and foods. In order to become bioactive at human body, these polyphenols must undergo diverse intestinal transformations, due to the action of digestive enzymes, but also by the action of microbiota metabolism. After elimination of sugar tailoring (generating the corresponding aglycons) and diverse hydroxyl moieties, as well as further backbone reorganizations, the final absorbed compounds enter the portal vein circulation towards liver (where other enzymatic transformations take place) and from there to other organs, including behind the digestive tract or via blood towards urine excretion. During this transit along diverse tissues and organs, they are able to carry out strong antiviral, antibacterial, and antiparasitic activities. This paper revises and discusses these antimicrobial activities of dietary polyphenols and their relevance for human health, shedding light on the importance of polyphenols structure recognition by specific enzymes produced by intestinal microbial taxa

Tolerance to paternal genotoxic damage promotes survival during embryo development in zebrafish (Danio rerio)

Spermatozoa carry DNA damage that must be repaired by the oocyte machinery upon fertilization. Different strategies could be adopted by different vertebrates to face the paternal genotoxic damage. Mammals have strong sperm selection mechanisms and activate a zygotic DNA damage response (DDR) (including cell cycle arrest, DNA repair and alternative apoptosis) in order to guarantee the genomic conformity of the reduced progeny. However, external fertilizers, with different reproductive strategies, seem to proceed distinctively. Previous results from our group showed a downregulation of apoptotic activity in trout embryos with a defective DNA repairing ability, suggesting that mechanisms of tolerance to damaged DNA could be activated in fish to maintain cell survival and to progress with development. In this work, zebrafish embryos were obtained from control or UV-irradiated sperm (carrying more than 10% of fragmented DNA but still preserving fertilization ability). DNA repair (γH2AX and 53BP1 foci), apoptotic activity, expression of genes related to DDR and malformation rates were analyzed throughout development. Results showed in the progeny from damaged sperm, an enhanced repairing activity at the mid-blastula transition stage that returned to its basal level at later stages, rendering at hatching a very high rate of multimalformed larvae. The study of transcriptional and post-translational activity of tp53 (ZDF-GENE-990415-270) revealed the activation of an intense DDR in those progenies. However, the downstream pro-apoptotic factor noxa (ZDF-GENE-070119-3) showed a significant downregulation, whereas the anti-apoptotic gene bcl2 (ZDF-GENE-051015-1) was upregulated, triggering a repressive apoptotic scenario in spite of a clear genomic instability. This repression can be explained by the observed upregulation of p53 isoform Δ113p53, which is known to enhance bcl2 transcription. Our results showed that tp53 is involved in DNA damage tolerance (DDT) pathways, allowing the embryo survival regardless of the paternal DNA damage. DDT could be an evolutionary mechanism in fish: tolerance to unrepaired sperm DNA could introduce new mutations, some of them potentially advantageous to face a changing environment

Transgenerational paternal inheritance of the toxic effects of bisphenol A

Bisphenol A (BPA) is an endocrine disruptor widespread used in manufacturing of food, drink and sanitary plastic devices as well as thermal paper, resulting in a long-term exposure in humans. Relevant concentrations of BPA in human urine have been related to different pathologies. Indeed, it is well known that either direct exposure to BPA or maternal exposure during pregnancy, promotes metabolic alterations, reproductive disorders or cardiovascular diseases. Epigenetic mechanisms are thought to represent the most plausible targets through which BPA could have long-lasting effects since it can accumulate in adipose tissue of testicles allowing modifications in spermatozoa DNA methylation pattern, thus affecting indirectly the offspring. In this scenario, the aim of our work is to assess whether paternal exposure to BPA causes changes in DNA methylation which could lie behind phenotypic alterations in the progeny

Embryonic exposure to bisphenol a impairs primordial germ cell migration without jeopardizing male breeding capacity

A large amount of chemicals are released to the environment each year. Among them, bisphenol A (BPA) is of utmost concern since it interferes with the reproductive system of wild organisms due to its capacity to bind to hormone receptors. Additionally, BPA epigenotoxic activity is known to affect basic processes during embryonic life. However, its effects on primordial germ cells (PGCs) proliferation and migration, both mechanisms being crucial for gametogenesis, remain unknown. To investigate the effects of BPA on PGCs migration and eventual testicle development, zebrafish embryos were exposed to 100, 2000 and 4000 µg/L BPA during the first 24 h of development. Vasa immunostaining of PGCs revealed that exposure to 2000 and 4000 µg/L BPA impaired their migration to the genital ridge. Two pivotal genes of PGCs migration (cxcr4b and sdf1a) were highly dysregulated in embryos exposed to these doses, whereas DNA methylation and epigenetic marks in PGCs and their surrounding somatic cells were not altered. Once embryos reached adulthood, the morphometric study of their gonads revealed that, despite the reduced number of PGCs which colonized the genital ridges, normal testicles were developed. Although H3K9ac decreased in the sperm from treated fishes, it did not affect the progeny development

A diet based on cured acorn-fed ham with oleic acid content promotes antiinflammatory gut microbiota and prevents ulcerative colitis in an animal model

Background: Diets based on meat products are not recommended in the case of ulcerative colitis (UC). The objective here is to test if some traditional cured meat products, as acorn-fed ham (high levels of oleic acid), may be useful for controlling inflammatory diseases as UC in animal models, which could represent a new dietary complementary intervention in the prevention of this inflammatory disease in humans. Methods: Two rat cohorts have been used: conventional vegetable rat feed and acorn-fed ham. UC was induced with DSS in drinking water ad libitum for 1 week. Short-chain fatty acids (SCFAs) and 16S rRNA metagenomics from bacterial populations were analyzed in cecum samples. Colon samples were analyzed for histological parameters. Results: Acorn-fed ham diet induced changes in gut microbiota composition, with pronounced enrichments in anti-inflammatory bacterial genera (Alistipes, Blautia, Dorea, Parabacteroides). The animals with this diet showed a strong reduction in most parameters associated to ulcerative colitis: disease activity index, macroscopic score of colitis, epitelium alteration in colon mucosa, inflammatory cell density in colon, myeloperoxidase titers in colon, proinflammatory cytokines (IL-17, IFN-γ). Also, acorn-fed ham diet animals showed increased total antioxidant activity an oleic acid levels in plasma, as well as higher short-chain fatty acid concentrations in cecum (isobutyric, isovaleric and valeric). Conclusions: In the acorn-fed ham cohort, as a result of the dietary intake of oleic acid and low intake of omega-6 fatty acids, a strong preventive effect against UC symptoms was observed. Keywords: Oleic acid, Acorn-fed ham, Gut microbiota, Ulcerative colitis, AntiiflammatoryCárnicas Joselito SA (FUO-222-16)Universidad de Oviedo y Universidad Complutense de Madrid (IDI/2018/000120) - Programa de Ayudas a Grupos de Investigación del Principado de Asturias.Depto. de Producción AnimalFac. de VeterinariaTRUEpu