Publications
243 results found
Lee YS, Marianoglou M, Hanton F, et al., 2017, D-Lactic Acid Inhibits Basal Inflammatory Pathways in Human Vaginal Epithelial Cells., 64th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 241A-241A, ISSN: 1933-7191
Lewis H, Pruski P, Kindinger L, et al., 2017, Relationship Between Yeast, Vaginal Microbiota Composition and Pregnancy Outcomes., 64th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 65A-65A, ISSN: 1933-7191
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- Citations: 1
Bobdiwala S, Al-Memar M, Lee Y, et al., 2017, Ectopic pregnancy is associated with increased vaginal bacterial diversity and reduced <i>Lactobacillus</i> species dominance, Publisher: WILEY, Pages: 63-64, ISSN: 1470-0328
Brown R, Lee Y, Kindinger L, et al., 2017, Vaginal dysbiosis following preterm prelabour rupture of the fetal membranes is associated with funisitis and the emergence of specific pathobionts, Publisher: WILEY, Pages: 31-31, ISSN: 1470-0328
Lewis H, Pruski P, Kindinger L, et al., 2017, Desorption electrospray ionisation mass spectrometry permits identification of vaginal mucosal metabolome signatures associated with preterm birth risk, Publisher: WILEY, Pages: 135-135, ISSN: 1470-0328
Al-Memar M, Bobdiwala S, Lee Y, et al., 2017, Association between vaginal microbiome dysbiosis and miscarriage, Publisher: WILEY, Pages: 65-65, ISSN: 1470-0328
Kindinger LM, Bennett PR, Lee YS, et al., 2017, The interaction between vaginal microbiota, cervical length and vaginal progesterone treatment for preterm birth risk, Microbiome, Vol: 5, Pages: 1-14, ISSN: 2049-2618
Background:Preterm birth is the primary cause of infant death worldwide. A short cervix in the second trimester of pregnancy is a risk factor for preterm birth. In specific patient cohorts, vaginal progesterone reduces this risk. Using 16S rRNA gene sequencing we undertook a prospective study in women at risk of preterm birth(n=161) to assess 1) the relationship between vaginal microbiotaand cervical length in the second trimester and preterm birth-risk, and 2) the impact of vaginal progesterone on vaginal bacterial communities in women with a short cervix.Results:Lactobacillus iners dominance at 16 weeks gestation was significantly associated with both a short cervix <25mm (n=15, P<0.05), andpreterm birth <34+0 weeks (n=18, 38P<0.01; 69% PPV).In contrast, L. crispatus dominance was highly predictive of term birth (n=127, 98% PPV). Cervical shortening and preterm birthwere not associated with vaginal dysbiosis. A longitudinal characterization of vaginal microbiota (<18, 22, 28 and 34 weeks)was then undertaken in women receiving vaginal progesterone (400mg/OD, n=25) versus controls (n=42).Progesterone did not alter vaginal bacterial community structurenor reduce L. iners-associated preterm birth (<34 weeks). Conclusions:L. iners dominance of the vaginal microbiota at 16 weeks gestation is a risk factor for preterm birth, whereas L. crispatus dominance is protective against preterm birth. Vaginal progesterone does not appear to impact the pregnancy vaginal microbiota. Patients and clinicians who may be concerned about ‘infection risk’ associated with use of a vaginal pessary during high-risk pregnancy can be reassured.
Khanjani S, MacIntyre DA, Bennett PR, 2017, Pathophysiology of Preterm Birth, Fetal and Neonatal Physiology, 2-Volume Set, Pages: 1732-1737.e2, ISBN: 9780323352338
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- Citations: 1
Jimenez B, MacIntyre D, 2017, NMR Metabolic Phenotyping in Clinical Studies, ENCYCLOPEDIA OF SPECTROSCOPY AND SPECTROMETRY, 3RD EDITION, VOL 3: N-R, Editors: Lindon, Tranter, Koppenaal, Publisher: ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD, Pages: 140-145
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- Citations: 3
Pruski P, MacIntyre DA, Lewis HV, et al., 2016, Medical swab analysis using desorption electrospray ionization mass spectrometry (DESI-MS) – a non-invasive approach for mucosal diagnostics, Analytical Chemistry, Vol: 89, Pages: 1540-1550, ISSN: 0003-2700
Medical swabs are routinely used worldwide to sample human mucosa for microbiological screening with culture methods. These are usually time-consuming and have a narrow focus on screening for particular microorganism species. As an alternative, direct mass spectrometric profiling of the mucosal metabolome provides a broader window into the mucosal ecosystem. We present for the first time a minimal effort/minimal-disruption technique for augmenting the information obtained from clinical swab analysis with mucosal metabolome profiling using desorption electrospray ionization mass spectrometry (DESI-MS) analysis. Ionization of mucosal biomass occurs directly from a standard rayon swab mounted on a rotating device and analyzed by DESI MS using an optimized protocol considering swab–inlet geometry, tip–sample angles and distances, rotation speeds, and reproducibility. Multivariate modeling of mass spectral fingerprints obtained in this way readily discriminate between different mucosal surfaces and display the ability to characterize biochemical alterations induced by pregnancy and bacterial vaginosis (BV). The method was also applied directly to bacterial biomass to confirm the ability to detect intact bacterial species from a swab. These results highlight the potential of direct swab analysis by DESI-MS for a wide range of clinical applications including rapid mucosal diagnostics for microbiology, immune responses, and biochemistry.
Begam Mohammed Rasheed Z, Lee Y, MacIntyre D, et al., 2016, Activation of the TLR 3 receptor: A possible mechanism for virally induced preterm labour, Society for Reproductive Investigation
Chan D, Lee Y, Teoh TG, et al., 2016, A comparison of TLR 1-9 induced cytokine responses in whole blood collected in the first trimester and at term and matched cord blood, Society for Reproductive Investigation
Sykes L, Anucha E, Begam Z, et al., 2016, The effect of TLR3 receptor priming on TLR 2, 4 and 6 agonist induced inflammation in placental implants, Society for Reproductive Investigation
Cacciatore S, Tenori L, Luchinat C, et al., 2016, KODAMA: an R package for knowledge discovery and data mining, Bioinformatics, ISSN: 1367-4803
KODAMA, a novel learning algorithm for unsupervised feature extraction, is specifically designed for analysing noisy and high-dimensional datasets. Here we present an R package of the algorithm with additional functions that allow improved interpretation of high-dimensional data. The package requires no additional software and runs on all major platforms.
Edey LF, O'Dea KP, Herbert BR, et al., 2016, The local and systemic immune response to intrauterine LPS in the prepartum mouse, Biology of Reproduction, Vol: 95, Pages: 1-10, ISSN: 1529-7268
Inflammation plays a key role in human term and preterm labor (PTL). Intrauterine LPS has been widely used to model inflammation-induced complications of pregnancy, including PTL. It has been shown to induce an intense myometrial inflammatory cell infiltration, but the role of LPS-induced inflammatory cell activation in labor onset and fetal demise is unclear. We investigated this using a mouse model of PTL, where an intrauterine injection of 10 μg of LPS (serotype 0111:B4) was given at E16 of CD1 mouse pregnancy. This dose induced PTL at an average of 12.7 h postinjection in association with 85% fetal demise. Flow cytometry showed that LPS induced a dramatic systemic inflammatory response provoking a rapid and marked leucocyte infiltration into the maternal lung and liver in association with increased cytokine levels. Although there was acute placental inflammatory gene expression, there was no corresponding increase in fetal brain inflammatory gene expression until after fetal demise. There was marked myometrial activation of NFκB and MAPK/AP-1 systems in association with increased chemokine and cytokine levels, both of which peaked with the onset of parturition. Myometrial macrophage and neutrophil numbers were greater in the LPS-injected mice with labor onset only; prior to labor, myometrial neutrophils and monocytes numbers were greater in PBS-injected mice, but this was not associated with an earlier onset of labor. These data suggest that intrauterine LPS induces parturition directly, independent of myometrial inflammatory cell infiltration, and that fetal demise occurs without fetal inflammation. Intrauterine LPS provokes a marked local and systemic inflammatory response but with limited inflammatory cell infiltration into the myometrium or placenta.
Al-Memar M, Caccitore S, Bobdiwala S, et al., 2016, Urine metabolomic changes by gestational age in early pregnancy and differences in the metabolome in viable pregnancies that miscarry compared to those that remain viable, Publisher: WILEY-BLACKWELL, Pages: E1-E1, ISSN: 1470-0328
Brown R, Kindinger L, Lee Y, et al., 2016, Characterisation of the vaginal microbiome in patients subsequently experiencing preterm prelabour rupture of membranes, Publisher: WILEY-BLACKWELL, Pages: E2-E3, ISSN: 1470-0328
Kindinger L, MacIntyre D, Lee Y, et al., 2016, Understanding the interaction between the cervix and the vaginal microbiome underlying specific aetiologies of preterm birth, Publisher: WILEY-BLACKWELL, Pages: E5-E6, ISSN: 1470-0328
Kindinger L, MacIntyre D, Lee Y, et al., 2016, Cervical cerclage using braided suture induces vaginal dysbiosis, inflammation and is associated with increased rates of preterm birth, Publisher: WILEY-BLACKWELL, Pages: E4-E4, ISSN: 1470-0328
Kindinger LM, Kyrgiou M, MacIntyre DA, et al., 2016, Preterm Birth Prevention Post-Conization: A Model of Cervical Length Screening with Targeted Cerclage, PLOS One, Vol: 11, ISSN: 1932-6203
Women with a history of excisional treatment (conization) for cervical intra-epithelial neoplasia (CIN) are at increased risk of preterm birth, perinatal morbidity and mortality in subsequent pregnancy. We aimed to develop a screening model to effectively differentiate pregnancies post-conization into low- and high-risk for preterm birth, and to evaluate the impact of suture material on the efficacy of ultrasound indicated cervical cerclage. We analysed longitudinal cervical length (CL) data from 725 pregnant women post-conization attending preterm surveillance clinics at three London university Hospitals over a ten year period (2004–2014). Rates of preterm birth <37 weeks after targeted cerclage for CL<25mm were compared with local and national background rates and expected rates for this cohort. Rates for cerclage using monofilament or braided suture material were also compared. Of 725 women post-conization 13.5% (98/725) received an ultrasound indicated cerclage and 9.7% (70/725) delivered prematurely, <37weeks; 24.5% (24/98) of these despite insertion of cerclage. The preterm birth rate was lower for those that had monofilament (9/60, 15%) versus braided (15/38, 40%) cerclage (RR 0.7, 95% CI 0.54 to 0.94, P = 0.008). Accuracy parameters of interval reduction in CL between longitudinal second trimester screenings were calculated to identify women at low risk of preterm birth, who could safely discontinue surveillance. A reduction of CL <10% between screening timepoints predicts term birth, >37weeks. Our triage model enables timely discharge of low risk women, eliminating 36% of unnecessary follow-up CL scans. We demonstrate that preterm birth in women post-conization may be reduced by targeted cervical cerclage. Cerclage efficacy is however suture material-dependant: monofilament is preferable to braided suture. The introduction of triage prediction models has the potential to reduce the number of unnecessary CL scan for women at low risk of
Mitra A, Macintyre DA, marchesi, et al., 2016, The vaginal microbiota, human papillomavirus infection and cervical intraepithelial neoplasia: what do we know and where are we going next?, Microbiome, Vol: 4, ISSN: 2049-2618
The vaginal microbiota plays a significant role in health and disease of the female reproductive tract. Next-generation sequencing techniques based upon analysis of bacterial 16S rRNA genes permits in-depth study of vaginal microbial community structure to a level of detail not possible with standard culture based microbiological techniques. The Human Papillomavirus (HPV) causes both cervical intraepithelial neoplasia (CIN) and cervical cancer. Although the virus is highly prevalent, only a small number of women have a persistent HPV infection and subsequently develop clinically significant disease. There is emerging evidence which leads us to conclude that increased diversity of vaginal microbiota combined with reduced relative abundance of Lactobacillus spp. is involved in HPV acquisition and persistence, and the development of cervical precancer and cancer. In this review we summarise the current literature, and discuss potential mechanisms for the involvement of vaginal microbiota in the evolution of CIN and cervical cancer. The concept of manipulation of vaginal bacterial communities using pre- and probiotics is also discussed as an exciting prospect for the field of cervical pathology.
Mitra A, MacIntyre D, Lee Y, et al., 2016, Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity, Blair Bell Research Society Annual Academic Meeting, Publisher: Wiley, Pages: E11-E12, ISSN: 1470-0328
Kindinger LM, MacIntyre DA, Lee YS, et al., 2016, Relationship between vaginal microbial dysbiosis, inflammation, and pregnancy outcomes in cervical cerclage., Sci Transl Med, Vol: 8
Preterm birth, the leading cause of death in children under 5 years, may be caused by inflammation triggered by ascending vaginal infection. About 2 million cervical cerclages are performed annually to prevent preterm birth. The procedure is thought to provide structural support and maintain the endocervical mucus plug as a barrier to ascending infection. Two types of suture material are used for cerclage: monofilament or multifilament braided. Braided sutures are most frequently used, although no evidence exists to favor them over monofilament sutures. We assessed birth outcomes in a retrospective cohort of 678 women receiving cervical cerclage in five UK university hospitals and showed that braided cerclage was associated with increased intrauterine death (15% versus 5%; P = 0.0001) and preterm birth (28% versus 17%; P = 0.0006) compared to monofilament suture. To understand the potential underlying mechanism, we performed a prospective, longitudinal study of the vaginal microbiome in women at risk of preterm birth because of short cervical length (≤25 mm) who received braided (n = 25) or monofilament (n = 24) cerclage under comparable circumstances. Braided suture induced a persistent shift toward vaginal microbiome dysbiosis characterized by reduced Lactobacillus spp. and enrichment of pathobionts. Vaginal dysbiosis was associated with inflammatory cytokine and interstitial collagenase excretion into cervicovaginal fluid and premature cervical remodeling. Monofilament suture had comparatively minimal impact upon the vaginal microbiome and its interactions with the host. These data provide in vivo evidence that a dynamic shift of the human vaginal microbiome toward dysbiosis correlates with preterm birth.
Migale R, MacIntyre DA, Cacciatore S, et al., 2016, Modeling hormonal and inflammatory contributions to preterm and term labor using uterine temporal transcriptomics, BMC Medicine, Vol: 14, ISSN: 1741-7015
BACKGROUND: Preterm birth is now recognized as the primary cause of infant mortality worldwide. Interplay between hormonal and inflammatory signaling in the uterus modulates the onset of contractions; however, the relative contribution of each remains unclear. In this study we aimed to characterize temporal transcriptome changes in the uterus preceding term labor and preterm labor (PTL) induced by progesterone withdrawal or inflammation in the mouse and compare these findings with human data. METHODS: Myometrium was collected at multiple time points during gestation and labor from three murine models of parturition: (1) term gestation; (2) PTL induced by RU486; and (3) PTL induced by lipopolysaccharide (LPS). RNA was extracted and cDNA libraries were prepared and sequenced using the Illumina HiSeq 2000 system. Resulting RNA-Seq data were analyzed using multivariate modeling approaches as well as pathway and causal network analyses and compared against human myometrial transcriptome data. RESULTS: We identified a core set of temporal myometrial gene changes associated with term labor and PTL in the mouse induced by either inflammation or progesterone withdrawal. Progesterone withdrawal initiated labor without inflammatory gene activation, yet LPS activation of uterine inflammation was sufficient to override the repressive effects of progesterone and induce a laboring phenotype. Comparison of human and mouse uterine transcriptomic datasets revealed that human labor more closely resembles inflammation-induced PTL in the mouse. CONCLUSIONS: Labor in the mouse can be achieved through inflammatory gene activation yet these changes are not a requisite for labor itself. Human labor more closely resembles LPS-induced PTL in the mouse, supporting an essential role for inflammatory mediators in human "functional progesterone withdrawal." This improved understanding of inflammatory and progesterone influence on the uterine transcriptome has important implications for
Al-Memar M, Cacciatore S, Bobdiwala S, et al., 2016, Urine metabolomic changes by gestational age in early pregnancy and differences in the metabolome in viable pregnancies that miscarry compared to those that remain viable, Publisher: Wiley, Pages: 76-76, ISSN: 1470-0328
Cook J, MacIntyre D, Sykes L, et al., 2016, Prediction of cervical shortening and preterm delivery using specific cell free plasma microRNAs, Publisher: Wiley, Pages: 59-60, ISSN: 1470-0328
Cook J, MacIntyre D, Kim SH, et al., 2016, Hsa-miR-146b-3p is functionally modulated by Nuclear Factor Kappa-B in human myometrial cells, Publisher: WILEY-BLACKWELL, Pages: 162-162, ISSN: 1470-0328
Cook J, MacIntyre D, Kim SH, et al., 2016, Hsa-miR-146b-3p is functionally modulated by nuclear factor-kappa B in human myometrial cells, British Maternal & Fetal Medicine Society (BMFMS) 18th Annual Conference 2016, Publisher: WILEY-BLACKWELL, Pages: 102-102, ISSN: 1470-0328
Cook J, MacIntyre D, Sykes L, et al., 2016, Expression of specific cell-free plasma microRNAs is associated with cervical shortening in women at risk of preterm birth, British Maternal & Fetal Medicine Society (BMFMS) 18th Annual Conference 2016, Publisher: WILEY-BLACKWELL, Pages: 103-103, ISSN: 1470-0328
Kindinger L, MacIntyre D, Lee Y, et al., 2016, Cervical cerclage using braided suture induces vaginal dysbiosis, inflammation, and is associated with increased preterm birth, British Maternal & Fetal Medicine Society (BMFMS) 18th Annual Conference 2016, Publisher: Wiley, Pages: 8-8, ISSN: 1470-0328
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