Projection of Gut Microbiome Pre- and Post-Bariatric Surgery To Predict Surgery Outcome.

Bariatric surgery is often the preferred method to resolve obesity and diabetes, with ∼800,000 cases worldwide yearly and high outcome variability. The ability to predict the long-term body mass index (BMI) change following surgery has important implications for individuals and the health care system in general. Given the tight connection between eating habits, sugar consumption, BMI, and the gut microbiome, we tested whether the microbiome before any treatment is associated with different treatment outcomes, as well as other intakes (high-density lipoproteins [HDL], triglycerides, etc.). A projection of the gut microbiome composition of obese (sampled before and after bariatric surgery) and lean patients into principal components was performed, and the relation between this projection and surgery outcome was studied. The projection revealed three different microbiome profiles belonging to lean, obese, and obese individuals who underwent bariatric surgery, with the postsurgery microbiome more different from the lean microbiome than the obese microbiome. The same projection allowed for a prediction of BMI loss following bariatric surgery, using only the presurgery microbiome. The microbial changes following surgery were an increase in the relative abundance of Proteobacteria and Fusobacteria and a decrease in Firmicutes. The gut microbiome can be decomposed into main components depicting the patient's development and predicting in advance the outcome. Those may be translated into the better clinical management of obese individuals planning to undergo metabolic surgery. IMPORTANCE BMI and diabetes can affect the gut microbiome composition. Bariatric surgery has large variabilities in the outcome. The microbiome was previously shown to be a good predictor for multiple diseases. We analyzed here the gut microbiome before and after bariatric surgery and showed the following. (i) The microbiome before surgery can be used to predict surgery outcomes. (ii) The postsurgery microbiome drifts further away from the lean microbiome than the microbiome of the presurgery obese patients. These results can lead to a microbiome-based presurgery decision whether to perform surgery.

A novel test for annexin A5 M2 haplotyping in in vitro fertilization patients and preimplantation embryos.

OBJECTIVE: To develop a test for evaluating the annexin A5 M2 haplotype in in vitro fertilization patients and preimplantation embryos. DESIGN: Test performance was measured by comparing Sanger sequencing of parental blood DNA and quantitative real-time polymerase chain reaction (qPCR) of saliva DNA, 3 fibroblast cell line 7-cell aliquots and their corresponding purified DNA, 123 trophectoderm biopsy samples, and DNA isolated from 1 embryonic stem cell line along with the Mendelian inheritance expectations, embryo Sanger sequencing, and single-nucleotide polymorphism (SNP) microarray-based linkage analysis. SETTING: Preimplantation genetic testing laboratory research on IVF patient and embryo DNA. PATIENT(S): An assay was developed for the detection of the M2 haplotype on saliva samples of 6 in vitro fertilization patients. In addition, 13 patients who underwent preimplantation genetic testing with data on parental and embryo biopsy DNA available for research use were evaluated. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The concordance rates between Sanger sequencing, SNP array-based linkage analysis, and Mendelian inheritance expectations with qPCR. RESULT(S): The concordance rate between Sanger sequencing and qPCR was 100% on parental blood DNA and saliva DNA. The sample concordance rate between all replicates of 7-cell aliquots was 100%. The sample concordance rate between 3 cell lines used to prepare 7-cell aliquots and purified genomic DNA was 100%. The concordance rate between qPCR and Sanger sequencing results from a single trophectoderm biopsy and isolated embryonic stem cell line was 100%. The concordance rate of trophectoderm biopsy qPCR results and expectations from Mendelian inheritance rules was 97%; however, when SNP array-based linkage analysis was included, the concordance rate reached 100%. CONCLUSION(S): This study resulted in the development of a convenient saliva collection method and qPCR-based genotyping method to screen for the M2 haplotype. In addition, a novel method for testing preimplantation embryos has been established, providing an alternative to the use of low molecular weight heparin, through selection of embryos without the M2 haplotype.

Preimplantation Genetic Testing for Polygenic Disease Relative Risk Reduction: Evaluation of Genomic Index Performance in 11,883 Adult Sibling Pairs.

Preimplantation genetic testing for polygenic disease risk (PGT-P) represents a new tool to aid in embryo selection. Previous studies demonstrated the ability to obtain necessary genotypes in the embryo with accuracy equivalent to in adults. When applied to select adult siblings with known type I diabetes status, a reduction in disease incidence of 45-72% compared to random selection was achieved. This study extends analysis to 11,883 sibling pairs to evaluate clinical utility of embryo selection with PGT-P. Results demonstrate simultaneous relative risk reduction of all diseases tested in parallel, which included diabetes, cancer, and heart disease, and indicate applicability beyond patients with a known family history of disease.