Biology subjects

Kousha, A.

Publications and source records attributed to Kousha, A..

4 recordsLinked to original sources

bioRxiv2025

Effect of Perinatal Ampicillin or Amoxicillin/Clavulanate Exposure on Maternal and Infant Gut Microbiome, Metabolome, and Infant Responses to the 20-valent Pneumococcal Conjugate Vaccine

Emerging studies suggest that antibiotics can disrupt the gut microbiome and alter vaccine-induced immune responses, but the specific consequences of early-life exposure on neonatal immune development remains poorly understood. Here, we examined how two antibiotics frequently used in perinatal care, broad-spectrum ampicillin (AMP) and the extended-spectrum combination amoxicillin/clavulanate (AMOX/CLAV), administered during gestation and lactation, influence neonatal gut microbiome composition, fecal metabolome profiles, and responses to the 20-valent pneumococcal conjugate vaccine (PCV20). Maternal treatment with AMOX/CLAV, but not AMP, significantly reduced PCV-specific IgG titers at 4-and 6-weeks post-prime immunization compared to untreated controls. Exclusive exposure to AMOX/CLAV also impaired neutrophil-mediated opsonophagocytic killing, indicating diminished antibody functionality. These effects were transient, with immune parameters normalizing by week 8 post-prime immunization. Metabolomic and microbiome profiling revealed that maternal AMP and AMOX/CLAV differentially perturbed specific metabolite classes including bile acids, N-acyl lipids, and indole-derivatives, as well as key commensal taxa including Bacteroidales and Coriobacteriales within the gut microbiota. Together, these findings reveal a previously underappreciated maternal-offspring route of antibiotic influence that transiently disrupts neonatal vaccine responsiveness through microbiome and metabolome alterations. These results highlight maternal antibiotic exposure as a modifiable factor shaping early-life immunity.

microbiology↗

bioRxiv2025

Influence of perinatal ampicillin exposure on maternal fecal microbial and metabolic profiles

Indirect exposure to antibiotics during early life, via maternal intrapartum antibiotic prophylaxis (IAP) or postpartum maternal antibiotic usage, is increasingly common and has been epidemiologically linked to altered growth and immune developmental trajectories in offspring. Nevertheless, the underlying mechanisms remain poorly understood. Here, we explored the effects of antepartum and postpartum maternal ampicillin administration on the dams fecal microbiome and metabolic profiles in vivo. Ampicillin caused a reproducible depletion of beneficial bacterial species belonging to the Muribaculaceae family, including Muribaculum intestinale and Duncaniella dubosii, and led to cohort-dependent enrichments of Enterococcus and Prevotella species. These microbial alterations were accompanied by substantial metabolic remodeling, characterized by elevated fecal acylcarnitines and dysregulation of the bile acids profile. Intriguingly, we identified two previously uncharacterized trihydroxylated bile acids conjugated to a hexose moiety, which appeared to be associated with antibiotic exposure across public metabolomics repositories. These alterations in the fecal maternal microbiome and metabolome coincided with increased weight gain in offspring, suggesting a possible role for maternal antibiotic exposure in shaping early developmental trajectories. Further studies are warranted to elucidate the long-term implications of these changes in infant health. IMPORTANCEPerinatal antibiotic administration is a critical intervention to reduce maternal and neonatal infections, including early-onset group B Streptococcus (GBS) disease, a major cause of neonatal mortality. Nevertheless, mounting evidence suggests that the use of broad-spectrum antibiotics during the perinatal period in mothers can affect infant gut microbiome development, with potential consequences for immune maturation and early development. Understanding how maternal antibiotic exposure affects the gut microbiome and metabolome is essential for uncovering the potential pathways by which maternal intervention may influence offspring outcomes and for guiding strategies that balance infection control with long-term infant health.

microbiology↗

bioRxiv2024

A synthetic skin microbial community (SkinCom) enables reproducible investigations of the human skin microbiome

Existing models of the human skin have aided our understanding of skin health and disease. However, they currently lack a microbial component, despite microbes demonstrated connections to various skin diseases. Here we present a robust, standardized model of the skin bacterial community (SkinCom) to support complex in vitro and in vivo investigations. Our methods lead to an accurate, reproducible, and diverse community formation of aerobic and anaerobic bacteria. Subsequent testing of SkinCom on the dorsal skin of mice allowed for DNA and RNA recovery from both the applied SkinCom and from dorsal skin, highlighting its practicality for in vivo studies and -omics analyses. Furthermore, our results indicate that 65.6% of the responses to common cosmetic chemicals in vitro were recapitulated in a human trial. Therefore, SkinCom represents a valuable, standardized tool for investigating microbe-metabolite interactions and facilitates the experimental design of in vivo studies targeting host-microbe relationships.

microbiology↗

bioRxiv2024

Perinatal ampicillin administration modulates murine bile acid metabolism in vivo - an observational study

Antibiotics are an indispensable tool of modern medicine, yet their impact extends beyond eliminating harmful bacteria to perturbing the commensal bacteria constituting the gut microbiome. This collateral damage is particularly significant in early life when the gut microbiome is still developing. In humans, antibiotic administration during infancy and childhood is associated with various long-term negative health outcomes. However, existing research has predominantly focused on the direct administration of antibiotics to infants, leaving uncertainties about whether indirect antibiotic exposure produces similar effects. Here, we use mouse models to investigate how three distinct routes of exposure to the commonly prescribed broad-spectrum antibiotic ampicillin influences parent and infant metabolism. These methods simulate major modes of both direct and indirect antibiotic exposure: intravenous antibiotic administration to the mother immediately before birth mimicking intrapartum antibiotic prophylaxis, antibiotic use by the mother during lactation, and direct administration to infants mimicking empiric antibiotic treatment for neonatal sepsis. Through untargeted metabolomics of fecal samples from mouse dams and infants, we identified one class of compounds, bile acids and related cholane steroids, as particularly sensitive to ampicillin treatment. Bile acids, produced by the host and extensively modified by the gut microbiome, serve as important mediators in the cross-talk between the microbiota and the host. Here, we detail the coordinated changes in bile acid metabolism in response to a commonly prescribed antibiotic, focusing on dams treated both pre- and postpartum. Additionally, we identify unique bile acids associated with weight gain in infant mice. ImportanceAntibiotics are widely used perinatally, administered to both parents and infants before, during, and after birth. While they can play a life-saving role, antibiotics also result in collateral damage to the beneficial microbes constituting the gut microbiome. These microbes have many important functions, particularly in the metabolism of small molecules in the body. One such group of molecules, bile acids, undergo extensive modifications by bacteria and may act as a "language" through which microbes communicate with the host. This observational study investigates the impact of the commonly prescribed antibiotic ampicillin on the metabolism of these molecules during childbirth. Our results indicate that ampicillin administration pre- or post-partum significantly alters the mothers bile acid metabolism, but has a minimal influence on infant bile acid levels. However, in all cases, ampicillin administration significantly increased infant weight, even when the antibiotic was solely administered to the mother.

pharmacology and toxicology↗