The Effect of Secretor Status and the Vaginal Microbiome on Birth Outcome

Mutations in the FUT2 gene that result in a lack of expression of histo-blood group antigens on secreted glycoproteins may shape the vaginal microbiota with consequences for birth outcome. To test this, we analysed the relationship between secretor status, vaginal microbiota and gestational length in an ethnically diverse cohort of 313 pregnant women, including 91 who delivered prematurely. Lactobacillus species were found to co-occur less often with other microbial taxa in non-secretors. Moreover, non-secretors with Lactobacillus spp. depleted vaginal microbiota in early pregnancy had significantly shorter gestational length than Lactobacillus spp. dominated non-secretors (mean of 245.5 (SD=44.5) versus 265.9 (23.6)); p=0.045), but not compared to Lactobacillus spp. dominated (261.8 (27.5)) and depleted (264.3 days (21.2)) secretors. In identifying a relationship between blood-group antigen expression and vaginal microbiota-host interactions, our results point towards stratification by secretor status as an important factor for considering preterm birth risk and prevention. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The study was funded by the March of Dimes. The funder had no role in the study design, data collection and analysis, and preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was conducted with approval of the NHS National Research Ethics Service (NRES) Committees London City and East (REC 12/LO/2003) and LondonStanmore (REC 14/LO/0328), and by the North of Scotland Research Ethics Service (REC 14/NS/1078). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All sequencing data used in this study has been made available in ENA database (Accession numbers ERR4864561 to ERR4865307). Python and R scripts used in support of the analyses are available at: https://github.com/samitkundu/FUT2. Further information and requests for supporting data, resources, and reagents should be directed to the Lead Contact: David MacIntyre (d.macintyre@imperial.ac.uk).