Human beta defensin levels and vaginal microbiome composition in post-menopausal women diagnosed with lichen sclerosus

Brunner, Alexandra; Medvecz, Márta; Makra, Nóra; Sárdy, Miklós; Komka, Kinga; Gugolya, Máté; Szabó, Dóra; Gajdács, Márió; Ostorházi, Eszter

doi:10.1038/s41598-021-94880-4

Cited by 13 publications

(6 citation statements)

References 31 publications

(34 reference statements)

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“…Overproduction of defensins translate into increased activation of fibroblasts and synthesis of the extracellular matrix, which promotes disease progression. This suggests the possibility of treating such conditions by modulating the composition of the microbiome contributing to this condition [ 115 ].…”

Section: Hbd-2 In Pregnancy and Infancymentioning

confidence: 99%

Human β-Defensin 2 and Its Postulated Role in Modulation of the Immune Response

Cieślik

Bagińska

Górski

et al. 2021

Cells

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Studies described so far suggest that human β-defensin 2 is an important protein of innate immune response which provides protection for the human organism against invading pathogens of bacterial, viral, fungal, as well as parasitical origin. Its pivotal role in enhancing immunity was proved in infants. It may also be considered a marker of inflammation. Its therapeutic administration has been suggested for maintenance of the balance of systemic homeostasis based on the appropriate composition of the microbiota. It has been suggested that it may be an important therapeutic tool for modulating the response of the immune system in many inflammatory diseases, offering new treatment modalities. For this reason, its properties and role in the human body discussed in this review should be studied in more detail.

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Section: Hbd-2 In Pregnancy and Infancymentioning

confidence: 99%

Human β-Defensin 2 and Its Postulated Role in Modulation of the Immune Response

Cieślik

Bagińska

Górski

et al. 2021

Cells

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“…Several recent studies have demonstrated an association between low levels of β-defensin-2 and numerous obstetric and gynecologic pathologies, including preterm birth, bacterial vaginosis, lichen sclerosis, sexually transmitted infections. 3,12,28,29 In regards to GBS specifically, prior in vitro work by Castro-Leyva et al demonstrated that when incubated with S. agalactiae, choriodecidual cells increased production of β-defensin-2. 30 Boldenow et al showed increased β-defensin-2 production by GBS-exposed amnion cells and also found that in bacterial culture, β-defensin-2 decreased GBS viability in a concentration-dependent manner.…”

Section: Results In the Setting Of What Is Knownmentioning

confidence: 99%

Cervicovaginal Microbial–Immune State and Group B Streptococcus Colonization in Pregnancy

McCoy,

Burris,

Gerson

et al. 2023

Am J Perinatol

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Objective Maternal colonization with Group B Streptococcus (GBS) is a significant risk factor for serious neonatal morbidity. There are limited data on how the cervicovaginal (CV) microbiota and host immune factor β-defensin-2 might influence GBS colonization in pregnant individuals. This study sought to determine if the CV microbiota is associated with GBS colonization in pregnant individuals, and if β-defensin-2 modifies this relationship. Study Design This was a secondary analysis of a prospective cohort study of pregnant individuals with singleton pregnancies who had CV microbiota specimens analyzed at 16 to 20, 20 to 24, and 24 to 28 weeks' gestation, along with a third trimester GBS rectovaginal (RV) culture (n = 492). Microbiota data were analyzed with 16S rRNA gene sequencing and classified into community state types (CSTs). Log-binomial multivariable regression was used to model associations between CST and GBS RV status and to calculate risk ratios. β-defensin-2, an immune factor known to modulate the relationship between CST and pregnancy outcomes, was examined as an effect modifier. Results Of 492 individuals, 34.3% were GBS RV + . Compared with individuals with CST I at 16 to 20 weeks, individuals with CST IV-A and CST II had a significantly elevated relative risk of subsequent GBS RV+ status. When stratified by high and low β-defensin-2 levels, β-defensin-2 was found to be an effect modifier of the association between CST IV-A and GBS RV+ status. In individuals with low β-defensin-2 levels, CST VI-A was associated with GBS RV+ status, but among individuals with high β-defensin-2 levels, there was no such association (interaction p-value = 0.03). Conclusion Pregnant individuals with CV microbiota characterized by CST IV-A and CST II had significantly elevated risk of GBS RV colonization in the third trimester compared with those with CST I, and β-defensin-2 was an effect modifier of the association between CST IV-A and GBS RV+ status. Future research should investigate if manipulation of the CV microbiota can prevent GBS colonization, thereby reducing intrapartum antibiotic prophylaxis and the risks of neonatal GBS infection. Key Points

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“…Microorganisms and inducible defensins mutually affect each other’s presence in the bladder; the resulting balance may also be affected by a number of external factors. Examination of HBD2 or HBD3 levels individually showed no association with microbial composition, but the combined effect of HBD2 and HBD3 [ 41 ] shows an increasingly pronounced difference in the abundance of the genera characteristic for the PH and BC groups; i.e., the higher the HBD2 and 3 levels, the greater the differences in the microbiome composition between the two groups. HBD3 is also bactericidal against some Gram-positive species, in addition to its ability to kill Gram-negative bacteria, which is also characteristic of HBD1–2 [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Bladder Tissue Microbiome Composition in Patients of Bladder Cancer or Benign Prostatic Hyperplasia and Related Human Beta Defensin Levels

et al. 2022

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Balance between the microbiome associated with bladder mucosa and human beta defensin (HBD) levels in urine is a dynamic, sensitive and host-specific relationship. HBD1—possessing both antitumor and antibacterial activity—is produced constitutively, while the inducible production of antibacterial HBD2 and HBD3 is affected by bacteria. Elevated levels of HBD2 were shown to cause treatment failure in anticancer immunotherapy. Our aim was to assess the relationship between microbiome composition characteristic of tumor tissue, defensin expression and HBD levels measured in urine. Tissue samples for analyses were removed during transurethral resection from 55 bladder carcinoma and 12 prostatic hyperplasia patients. Microbiome analyses were carried out with 16S rRNS sequencing. Levels of HBD mRNA expression were measured with qPCR from the same samples, and urinary amounts of HBD1, 2 and 3 were detected with ELISA in these patients, in addition to 34 healthy volunteers. Mann–Whitney U test, Wilcoxon rank sum test (alpha diversity) and PERMANOVA analysis (beta diversity) were performed. Defensin-levels expressed in the tumor did not clearly determine the amount of defensin measurable in the urine. The antibacterial and antitumor defensin (HBD1) showed decreased levels in cancer patients, while others (HBD2 and 3) were considerably increased. Abundance of Staphylococcus, Corynebacterium and Oxyphotobacteria genera was significantly higher, the abundance of Faecalibacterium and Bacteroides genera were significantly lower in tumor samples compared to non-tumor samples. Bacteroides, Parabacteroides and Faecalibacterium abundance gradually decreased with the combined increase in HBD2 and HBD3. Higher Corynebacterium and Staphylococcus abundances were measured together with higher HBD2 and HBD3 urinary levels. Among other factors, defensins and microorganisms also affect the development, progression and treatment options for bladder cancer. To enhance the success of immunotherapies and to develop adjuvant antitumor therapies, it is important to gain insight into the interactions between defensins and the tumor-associated microbiome.

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Human beta defensin levels and vaginal microbiome composition in post-menopausal women diagnosed with lichen sclerosus

Cited by 13 publications

References 31 publications

Human β-Defensin 2 and Its Postulated Role in Modulation of the Immune Response

Human β-Defensin 2 and Its Postulated Role in Modulation of the Immune Response

Cervicovaginal Microbial–Immune State and Group B Streptococcus Colonization in Pregnancy

Bladder Tissue Microbiome Composition in Patients of Bladder Cancer or Benign Prostatic Hyperplasia and Related Human Beta Defensin Levels

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