Pre-conceptional microbiome alterations in women with recurrent spontaneous abortion: a pilot study

Abstract Recurrent spontaneous abortion (RSA) remains one of the greatest challenges in reproductive medicine. In many cases, the underlying cause cannot be identified. The gut microbiome plays a crucial role in maintaining health and contributing to disease development, and alterations in its composition have been linked to numerous chronic diseases. However, little is known about the role of the gut microbiome in the pathogenesis of miscarriage. In this study, we analyzed differences in the pre-conceptional microbiome composition of fifteen women with unexplained RSA and twenty-two healthy controls with at least one prior successful pregnancy and no history of miscarriage. Samples were collected​ in Germany between February 2021 and May 2023. Microbial taxonomic alpha and beta diversity as well as differential abundance of taxa were assessed by 16 s rRNA sequencing. Differential expression of serum acyl-carnitines and amino acids was assessed by tandem mass spectrometry. Women with RSA exhibited significantly reduced microbial alpha diversity, as assessed by the Shannon and Simpson indices, compared to controls. Beta diversity analysis revealed a continuous compositional shift between groups along the primary principal coordinate. At the phylum level, RSA was associated with a reduced relative abundance of Firmicutes and an increased abundance of Bacteroidota , resulting in a significantly lower Firmicutes/Bacteroidota ratio. Genus-level analysis suggested differences in relative abundances between RSA patients and controls, but none remained statistically significant after correction for multiple testing. Functional prediction suggested potential alterations in pathways related to lipopolysaccharide biosynthesis and amino acid degradation in RSA-associated microbiomes. Serum metabolomics revealed reduced tryptophan levels in RSA patients. Our findings suggest that specific pre-conceptional existing gut microbiome and serum metabolic alterations may be linked to the risk for RSA. Larger cohort studies and functional characterization of these changes are warranted to validate the translational potential of our results.