Impacts of ceftriaxone exposure during pregnancy on maternal gut and placental microbiota and its influence on maternal and offspring immunity in mice

Abstract

This study aimed to investigate the association between microbiota found in the maternal gut and placenta, and whether ceftriaxone exposure during pregnancy could alter these microbiota, and consequently affect the immunity of the mothers and their offspring. The microbiota in the feces and placenta of the dams were comprehensively analyzed using16S rRNA sequencing. Furthermore, viable bacteria in the placentas and blood of pups were also isolated by plate cultivation then taxonomically identified in detail by clone sequencing. Serum cytokines collected from dams and pups were quantitatively profiled using Luminex. The spleen organ index of dams was significantly lower and the offspring serum interleukin-6 levels were significantly higher in ceftriaxone-treated mice compared with the control group. The maternal fecal microbiota community was drastically altered in ceftriaxone-treated mice with significantly decreased diversity, depletion of Bacteroidetes and the blooming of Tenericutes. However, the placenta microbiota was dominated by Proteobacteria especially characteristically by Ralstonia, which was distinct from the maternal gut microbiota, regardless of whether ceftriaxone treatment or not. Viable bacteria have been found in placenta and blood cultures. These results indicated that ceftriaxone exposure in pregnancy could dramatically alter maternal intestinal microbiota, which affected the immunity of the mothers and their offspring at least partly, characteristically by enhanced pro-inflammatory responses. This study also indicated that the placenta might harbor its own microbes and the microbes were distinct from maternal gut microbiota, which may not be affected by oral administration of ceftriaxone during pregnancy.

Maternal gestational Bifidobacterium bifidum TMC3115 treatment shapes construction of offspring gut microbiota and development of immune system and induces immune tolerance to food allergen

“…However, current population and animal experimental studies have suggested that the first microbial exposure of newborns may occur before birth, and this exposure may have a regulatory effect on the development of the newborn’s immune system ( Collado et al., 2016 ; Gomez de Agüero et al., 2016 ). Our previous study found microorganisms in the placenta and cultured live bacteria from the blood of the newborn mice and the placenta, further verifying that microbial contact with the newborn might exist before birth ( Cheng et al., 2021 ). The maternal microbiota is considered to be the largest source of the gut microbiota of newborns, whereas the microbes of the vagina, skin, and oral cavity account for only a small proportion of the newborn gut microbiota, suggesting that the maternal microbiota has an important effect on the early gut microbiota of the offspring ( Shao et al., 2019 ).…”

Microbial composition of egg component and its association with hatchability of laying hens

“…The egg white mainly plays a role in resisting bacterial invasion and provides nutrients to the embryo, which has been reported as necessary for the start of embryo development (Willems et al, 2014). Several studies have confirmed that certain functional proteins in eggs can influence hatchability (Muramatsu et al, 1990;Rehault-Godbert et al, 2014;Cheng et al, 2021). Other studies in mammals have demonstrated that microbiota from various maternal sites during pregnancy may potentially influence the health and passive immunity of offspring.…”

Effectiveness of Cefixime for the Treatment of Neisseria gonorrhoeae Infection at 3 Anatomic Sites: A Systematic Review and Meta-Analysis

“…However, concerns have been raised about the availability of ceftriaxone. The ease of one-time oral administration of cefixime may justify the continued use of cefixime in certain settings 8,9 …”

“…The ease of one-time oral administration of cefixime may justify the continued use of cefixime in certain settings. 8 , 9 …”

“…The ease of one-time oral administration of cefixime may justify the continued use of cefixime in certain settings. 8,9 Recent data from the CDC's Gonococcal Isolate Surveillance Project have raised questions about the appropriate dosage of cefixime in the treatment of gonorrhea. Although cefixime minimal inhibitory concentrations rose steadily over the past 30 years, this trend has recently reversed in the United States, Canada, and England.…”