Biology subjects

Bernabe, B. P.

Publications and source records attributed to Bernabe, B. P..

3 recordsLinked to original sources

bioRxiv2025

Fetal sex is associated with the maternal gut microbiota composition and its metabolic function

BackgroundPregnancy affects almost every organ and system, including the microorganisms that resides in the gastrointestinal track, the gut microbiota. Pregnancy hormones, such as progesterone and estradiol, alter the composition of the maternal gut microbiota, directly and indirectly, and in turn, the gastrointestinal microorganism can modify the activity of reproductive hormones. While the levels of pregnancy hormones depend on the fetal sex, the role of fetal sex in the maternal gut microbiota composition and function has not been explored yet. MethodsUsing publicly available microbial sequencing data from a cohort of 485 pregnant women in Guangzhou, China, we identified taxonomical and predicted metabolic signatures associated with fetal sex and gestational age using zero-inflated Gaussian models and linear models, respectively, correcting for pre-pregnancy BMI, maternal age, parity, and residency status. Further, we determined sex-specific co-abundance microbial networks using SPIEC-EASI. ResultsWe observed higher diversity levels in male than in female pregnancies and identified multiple microbial species and predicted microbial enzymes that were differentially abundant between the fetal sex groups, such as increased levels of Tyzerrella and {beta}-glucuronidase in female pregnancies, respectively. {beta}-glucuronidase deconjugates glucuronide-bound estrogens into free estrogens and glucuronic acid. Further, the microbial co-abundance networks between the male and female pregnancies were distinct, with efficient information transfer being representative of the female network while the male network was characterized by a larger number of competitive or exclusion interactions between microbial species. While the two networks had similar core communities, there were distinct connections between hormone metabolizing microbes, with {beta}-glucuronidase expressing microbes being more highly connected in the female network. ConclusionsOur study suggests that differences in the maternal-fetal interactions, such as fetus/placenta-produced hormone levels, may affect and be affected by the composition of the gut microbiota of pregnant individuals in a sex-specific manner. A better understanding of the relationship between fetal sex and the maternal gut microbiota may improve maternal health and fetal outcomes. Plain English SummaryThe adequate functioning of the microbial communities that reside in the maternal gastrointestinal tract is essential for normal fetal development and their abnormal behavior has been associated with multiple conditions such as preterm birth, gestational diabetes, or depression. Yet, male and female fetuses interact differently with the maternal systems, in part due to the differences in fetal/placental-produced sex hormones. As studies outside pregnancy have shown that estrogen and progesterone metabolites can affect and be affected by the gut microbiota, fetal sex may have direct and indirect effects on maternal outcomes. Understanding these differences could enable better tailoring of prenatal care. HighlightsO_LIFetal/placental-produced sex hormones may affect and be affected by the maternal gut microbiota composition and its metabolic functions. C_LIO_LIGut microbiota diversity and composition during pregnancy is linked to the fetal sex. C_LIO_LIBacterially produced beta-glucuronidase (GUS), an enzyme that can deconjugate glucuronide-bound estrogens into free glucuronic acid and free estrogen, is increased in pregnancies with female fetuses, plausibly due higher levels of glucuronide-bound estrogens in female pregnancies that benefit GUS-expressing bacterial species that consume glucuronic acid C_LIO_LIThe maternal co-abundance gut microbial communities (networks) are distinct in pregnancies with female versus male fetuses specially among taxa that could produce GUS. C_LI

bioinformatics↗

bioRxiv2021

Gestational insulin resistance is mediated by the gut microbiome-indoleamine 2,3-dioxygenase axis

Background and aimsNormal gestation involves reprogramming of maternal gut microbiome (GM) that may contribute to maternal metabolic changes by unclear mechanisms. This study aimed to understand the mechanistic underpinnings of GM - maternal metabolism interaction. MethodsThe GM and plasma metabolome of CD1, NIH-Swiss and C57BL/6J mice were analyzed using 16S rRNA sequencing and untargeted LC-MS throughout gestation and postpartum. Pharmacologic and genetic knockout mouse models were used to identify the role of indoleamine 2,3-dioxygenase (IDO1) in pregnancy-associated insulin resistance (IR). Involvement of gestational GM in the process was studied using fecal microbial transplants (FMT). ResultsSignificant variation in gut microbial alpha diversity occurred throughout pregnancy. Enrichment in gut bacterial taxa was mouse strain and pregnancy time-point specific, with species enriched at gestation day 15/19 (G15/19), a point of heightened IR, distinct from those enriched pre- or post- pregnancy. Untargeted and targeted metabolomics revealed elevated plasma kynurenine at G15/19 in all three mouse strains. IDO1, the rate limiting enzyme for kynurenine production, had increased intestinal expression at G15, which was associated with mild systemic and gut inflammation. Pharmacologic and genetic inhibition of IDO1 inhibited kynurenine levels and reversed pregnancy-associated IR. FMT revealed that IDO1 induction and local kynurenine levels effects on IR derive from the GM in both mouse and human pregnancy. ConclusionsGM changes accompanying pregnancy shift IDO1-dependent tryptophan metabolism toward kynurenine production, intestinal inflammation and gestational IR, a phenotype reversed by genetic deletion or inhibition of IDO1.

physiology↗

bioRxiv2019

The human microbiota is associated with cardiometabolic risk across the epidemiologic transition

Oral and fecal microbial biomarkers have previously been associated with cardiometabolic (CM) risk, however, no comprehensive attempt has been made to explore this association in minority populations or across different geographic regions. We characterized gut- and oral-associated microbiota and CM risk in 655 participants of African-origin, aged 25-45, from Ghana, South Africa, Jamaica, and the United States (US). CM risk was classified using the CM risk cut-points for elevated waist circumference, elevated blood pressure and elevated fasted blood glucose, low high-density lipoprotein (HDL), and elevated triglycerides. Gut-associated bacterial alpha diversity negatively correlated with elevated blood pressure and elevated fasted blood glucose. Similarly, gut bacterial beta diversity was also significantly differentiated by waist circumference, blood pressure, triglyceridemia and HDL-cholesterolemia. Notably, differences in inter- and intra-personal gut microbial diversity were geographic-region specific. Participants meeting the cut-points for 3 out of the 5 CM risk factors were significantly more enriched with Lachnospiraceae, and were significantly depleted of Clostridiaceae, Peptostreptococcaceae, and Prevotella. The predicted relative proportions of the genes involved in the pathways for lipopolysaccharides (LPS) and butyrate synthesis were also significantly differentiated by the CM risk phenotype, whereby genes involved in the butyrate synthesis via lysine, glutarate and 4-aminobutyrate/succinate pathways and LPS synthesis pathway were enriched in participants with greater CM risk. Furthermore, inter-individual oral microbiota diversity was also significantly associated with the CM risk factors, and oral-associated Streptococcus, Prevotella, and Veillonella were enriched in participants with 3 out of the 5 CM risk factors. We demonstrate that in a diverse cohort of African-origin adults, CM risk is significantly associated with reduced microbial diversity, and the enrichment of specific bacterial taxa and predicted functional traits in both gut and oral environments. As well as providing new insights into the associations between the gut and oral microbiota and CM risk, this study also highlights the potential for novel therapeutic discoveries which target the oral and gut microbiota in CM risk.

microbiology↗