Objective Due to the global increase in obesity rates and success of bariatric surgery in weight reduction, an increasing number of women now present pregnant with a previous bariatric procedure. This study investigates the extent of bariatric-associated metabolic and gut microbial alterations during pregnancy and their impact on fetal development.
Design A parallel metabonomic (molecular phenotyping based on proton nuclear magnetic resonance spectroscopy) and gut bacterial (16S ribosomal RNA gene amplicon sequencing) profiling approach was used to determine maternal longitudinal phenotypes associated with malabsorptive/mixed (n=25) or restrictive (n=16) procedures, compared with women with similar early pregnancy body mass index but without bariatric surgery (n=70). Metabolic profiles of offspring at birth were also analysed.
Results Previous malabsorptive, but not restrictive, procedures induced significant changes in maternal metabolic pathways involving branched-chain and aromatic amino acids with decreased circulation of leucine, isoleucine and isobutyrate, increased excretion of microbial-associated metabolites of protein putrefaction (phenylacetlyglutamine, p-cresol sulfate, indoxyl sulfate and p-hydroxyphenylacetate), and a shift in the gut microbiota. The urinary concentration of phenylacetylglutamine was significantly elevated in malabsorptive patients relative to controls (p=0.001) and was also elevated in urine of neonates born from these mothers (p=0.021). Furthermore, the maternal metabolic changes induced by malabsorptive surgery were associated with reduced maternal insulin resistance and fetal/birth weight.
Conclusion Metabolism is altered in pregnant women with a previous malabsorptive bariatric surgery. These alterations may be beneficial for maternal outcomes, but the effect of elevated levels of phenolic and indolic compounds on fetal and infant health should be investigated further.
- enteric bacterial microflora
- colonic fermentation
- colonic bacteria
- gastric surgery
- obesity surgery
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KAW and CK contributed equally.
Contributors EH, MDS, JVL and MRJ designed the study. CK and TM recruited patients and collected biospecimens. KAW, CK and JAKM performed the experiments. KAW analysed the data. All authors contributed to the interpretation of results. KAW, MDS and EH wrote the manuscript. All authors read and approved the final manuscript.
Funding The study was supported partially by BORNE (UK Registered Charity number: 1167073).
Disclaimer The funding body did not contribute to the design of the study, collection, analysis, interpretation of data or writing the manuscript.
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval The study was approved by the West London Research Ethics Committee (No: 14/LO/0592).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available upon reasonable request. Raw sequencing data are available in a public, open access repository: Sequence Read Archive under BioProject PRJNA493625. Raw NMR data are available upon reasonable request. All pre-processed data and code to reproduce the results are available in a public, open access repository: GitHub (https://github.com/ka-west/PBS_manuscript). The R script is also included as a pdf file created with ‘knitr’ (see online supplementary methods).
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