Hanna Danielsson

Preterm birth is a major cause of neonatal morbidity and mortality worldwide. Increasing evidence links the vaginal microbiome to the risk of spontaneous preterm labour that leads to preterm birth. The aim of this systematic review and network meta-analysis was to investigate the association between the vaginal microbiome, defined as community state types (CSTs, i.e. dominance of specific lactobacilli spp, or not (low-lactobacilli)), and the risk of preterm birth. Systematic review using PubMed, Web of Science, Embase and Cochrane library was performed. Longitudinal studies using culture-independent methods categorizing the vaginal microbiome in at least three different CSTs to assess the risk of preterm birth were included. A (network) meta-analysis was conducted, presenting pooled odds ratios (OR) and 95% confidence intervals (CI); and weighted proportions and 95% CI. All 17 studies were published between 2014 and 2021 and included 38-539 pregnancies and 8-107 preterm births. Women presenting with "low-lactobacilli" vaginal microbiome were at increased risk (OR 1.69, 95% CI 1.15-2.49) for delivering preterm compared to Lactobacillus crispatus dominant women. Our network meta-analysis supports the microbiome being predictive of preterm birth, where low abundance of lactobacilli is associated with the highest risk, and L. crispatus dominance the lowest.

An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies and immune cell profiling, complemented with gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.

An important issue for the performance and specificity of an antibody is the nature of the binding to its protein target, including if the recognition involves linear or conformational epitopes. Here, we dissect polyclonal sera by creating epitope-specific antibody fractions using a combination of epitope mapping and an affinity capture approach involving both synthesized peptides and recombinant protein fragments. This allowed us to study the relative amounts of antibodies to linear and conformational epitopes in the polyclonal sera as well as the ability of each antibody-fraction to detect its target protein in Western blot assays. The majority of the analyzed polyclonal sera were found to have most of the target-specific antibodies directed towards linear epitopes and these were in many cases giving Western blot bands of correct molecular weight. In contrast, many of the antibodies towards conformational epitopes did not bind their target proteins in the Western blot assays. The results from this work have given us insights regarding the nature of the antibody response generated by immunization with recombinant protein fragments and has demonstrated the advantage of using antibodies recognizing linear epitopes for immunoassay involving wholly or partially denatured protein targets.

OBJECTIVES: To assess the impact of gestational antibiotics on the risk of preterm birth, since a healthy maternal microbiome may be protective. METHODS: Population-based cohort study including all first pregnancies in Sweden (2006-16). The association between gestational and recent pre-conception systemic antibiotics and preterm birth was assessed by multivariable logistic regression presented as ORs and 95% CIs, adjusted for comorbidities (hypo- and hyperthyroidism, hypertension, or diabetes mellitus pre-gestation), trimester, antibiotic class and treatment duration. RESULTS: Compared with non-users, antibiotic exposure was associated with increased risks of preterm birth in mothers with comorbidities (OR = 1.32, 95% CI 1.18-1.48) and without (OR = 1.09, 95% CI 1.06-1.13). Pre-conception use showed no association, while risk was increased for first and second trimester use and decreased for third trimester use. The increased risks were seen for the following antibiotic groups in mothers without and with comorbidities, respectively: macrolides, lincosamides and streptogramins (OR = 1.63, 95% CI 1.45-1.83; OR = 2.48, 95% CI 1.72-3.56); quinolones (OR = 1.60, 95% CI 1.32-1.94; OR = 2.11, 95% CI 1.12-4.03); non-penicillin β-lactams (OR = 1.15, 95% CI 1.07-1.24; OR = 1.39, 95% CI 1.07-1.83); other antibacterials (OR = 1.09, 95% CI 1.03-1.14; 1.38, 95% CI 1.16-1.63); and penicillins (OR = 1.04, 95% CI 1.01-1.08; 1.23, 95% CI 1.09-1.40). Antibiotic indications were not available, which could also affect preterm birth. CONCLUSIONS: Antibiotic use during pregnancy was associated with an increased risk of preterm birth, especially in mothers with chronic diseases.