DL-Citrulline

Delivery mode is recognized as an important determinant of gut microbiota composition. Vaginally delivered infants were colonized by maternal vaginal and fecal microbiota, while those delivered by cesarean section were colonized by environmental microorganisms. To reveal differences induced by delivery mode, we determined fecal microbiota and fecal metabolome from 60 infants in Northeast China region. Bacterial gene sequence analysis showed that the feces of vaginally delivered infants had the highest abundance of Bifidobacterium, Lactobacillus, Bacteroides and Parabacteroides, while the feces of cesarean section delivered infants were more enriched in Klebsiella. LC-MS-based metabolomics data demonstrated that the feces of vaginally delivered infants were associated with high abundance of DL-norvaline and DL-citrulline, while the feces of cesarean section delivered infants were abundant in trans-vaccenic acid and cis-aconitic acid. Moreover, the feces of vaginally delivered infants was significantly in positive correlation with tryptophan metabolism and pyruvate metabolism, however, the feces of cesarean section delivered infants was positively correlated with ABC transporters. Collectively, our study demonstrated that gut microbiota and metabolite profiles were significantly different between vaginally delivered and cesarean section delivered infants, and provided the theoretical basis for restoring the intestinal environment of cesarean section infants birthed in the study region. SIGNIFICANCE: The intestinal microbiota and metabolites play important roles in infant development. To validate whether delivery modes influence the gut environment, we performed a detailed analysis of the earliest microbial colonization of the infant gut using a combination of 16S rRNA gene amplicon sequencing and LC-MS-based metabolomics. We found that the gut microbiota and metabolite composition were significantly different between vaginally delivered infants and cesarean section delivered infants. Our findings establish a vital baseline for studies tracking the infant gut microbiota and metabolite development following different delivery modes, and their associated effects on infant health. This study provides preliminary evidence that the observed differences due to delivery modes highlight their importance in shaping the early intestinal microbiota and metabolites.

Premature rupture of membranes (PROM) is usually associated with pregnant and neonatal complications. Most of the PROM cases are caused by ascending asymptomatic genital infection. In China, PROM (15.3%) is more common than spontaneous preterm labor (7.3%) and leads to more adverse pregnancy outcomes. Here, we designed a prospective cohort study to measure the metabolomics changes in vaginal swab samples and explored their potential contribution to PROM. A total of 260 differentially expressed metabolites were identified and further analyzed. In the PROM group, N-acetyl-D-galactosamine and sucrose were downregulated (P = 0.0025, P = 0.0195, respectively), both of which are the upstream metabolites of the glycolysis pathway. Furthermore, estriol 3-sulfate 16-glucuronide (P = 0.0154) and 2-methoxy-17beta-estradiol 3-glucosiduronic acid (P = 0.004), two final metabolites in steroid hormone biosynthesis, were both downregulated in the PROM group. Finally, we found two catechin metabolites (epigallocatechin-7-glucuronide, P = 0.0009; 4'-methyl-epigallocatechin-7-glucuronide, P = 0.01) as well as DL-citrulline (P = 0.0393) were also significantly downregulated in the PROM group compared with the healthy control (HC) group, which are related to important antioxidant and anti-inflammatory activities in the human body. Altogether, metabolite changes in glycolysis, steroid hormone biosynthesis, and antioxidant/anti-inflammatory pathways may contribute to (or be a consequence of) vaginal dysbiosis and PROM. Metabolite pathway analysis is a new and promising approach to further investigate the mechanism of PROM and help prevent its unfavorable pregnant outcomes at a functional level. Trial registration number: ChiCTR2000034721.

Manipulating phase separation structures of thermoresponsive polymers will enhance the usefulness of structure-controllable materials in fields such as drug delivery and tissue engineering. However, behaviors of upper critical solution temperature (UCST) have been less investigated so far, despite the importance of UCST. Here, we examined two citrulline-based polypeptides, poly(d-ornithine- co-d-citrulline) (PdOC) and poly(dl-ornithine- co-dl-citrulline) (PdlOC), to investigate how stereoregularity of the polypeptides influences UCST behavior, in addition to poly(l-ornithine- co-l-citrulline) (PlOC) previously studied. Homochiral PlOC and PdOC showed phase separation temperatures ( Tps) higher than that of racemic PdlOC. Moreover, PdlOC underwent liquid to coacervate phase separation at Tp, whereas PlOC and PdOC underwent liquid to solid-like aggregation transitions. From a structural point of view, circular dichroism and small-angle X-ray scattering measurements revealed that homochiral PlOC and PdOC polypeptides formed α-helical structures and assembled into a regular hexagonal lattice upon phase separation. Interactions between the pendent ureido groups of homochiral POCs appear to play pivotal roles in helical folding and assembly into the hexagonal structure. In addition, Tp change in response to biodegradation was confirmed for both PlOC and PdlOC. The biodegradability was considerably influenced by phase-separated structures. These findings of UCST-type POCs in this study would provide important insights into structure-controllable and thermoresponsive biomaterials.