Biology subjects

Tsunoda, S. M.

Publications and source records attributed to Tsunoda, S. M..

8 recordsLinked to original sources

bioRxiv2026

Pan-Metabolomics Repository Mapping of the Carnitine Landscape

Carnitines are a structurally diverse class of metabolites formed by conjugation of L-carnitine with fatty acids, amino acids, xenobiotics, and microbial metabolites. They play roles in transport, mitochondrial and peroxisomal metabolism, detoxification, and systemic signaling, yet their chemical diversity remains incompletely defined. We applied a pan-repository data mining strategy of LC-MS/MS data across GNPS/MassIVE, MetaboLights, and Metabolomics Workbench using MassQL diagnostic fragment ion filtering to systematically extract acylcarnitine spectra. This yielded a library of 34,222 unique MS/MS spectra representing 2,857 atomic compositions, corresponding to 3,872,050 detections. These datasets provide an MS/MS library for annotation, discovery, and contextualization of acylcarnitines, enabling identification of previously unknown carnitines, such as dihydroferulic acid conjugated carnitines and supporting future exploration of this metabolite class across host metabolism, diet, microbial activity, pharmacological exposures, and metabolic dysregulation.

bioinformatics↗

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

Environmental and Maternal Imprints on Infant Gut Metabolic Programming

Early life is a critical period for immune and metabolic programming, but developmental patterns remain underexplored in populations from low- and middle-income countries. Here, we profiled the microbiome and metabolome of 55 Bangladeshi mother-infant dyads over the first six months of life. Importantly, we observed an increase in microbially-derived bile amidates and N-acyl lipids with age in conjunction with reads matching the bile salt hydrolase/transferase (bsh) gene. While microbial source tracking confirmed maternal fecal seeding, a substantial environmental contribution was also highlighted. Differences in infant fecal metabolic profiles were associated with delivery mode, maternal milk composition, household assets, and household-level water treatment. C-section delivery and untreated drinking water were linked to transient metabolic differences, including increases in bile amidates, N-acyl lipids, and other host-microbe co-metabolic products, including acylcarnitines. Multi-omics analysis revealed specific microbial-metabolite relationships, highlighting how early environmental and maternal living circumstances shape metabolic gut programming through the microbiome.

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↗

bioRxiv2025

Fecal Microbial and Metabolic Signatures in VEO-IBD: Implications for Unique Pathophysiology

Background and AimsVery early onset inflammatory bowel disease (VEO-IBD) is a clinically distinct form of IBD manifesting in children before the age of six years. Disease in these children is especially severe and often refractory to treatment. While previous studies have investigated changes in the fecal microbiome and metabolome in adult and pediatric IBD, insights in VEO-IBD remain limited. This multi-omics analysis reveals changes in the fecal microbiome and metabolome in VEO-IBD compared with healthy controls. MethodsFecal samples were collected from children diagnosed with VEO-IBD and age- and sex-matched healthy controls. Both the fecal metabolome and microbiome were profiled in each sample, using untargeted liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and 16S rRNA gene amplicon sequencing. ResultsFecal microbial and metabolic profiles in VEO-IBD were significantly different from healthy controls. Untargeted metabolomics analysis identified a depletion of short-chain N-acyl lipids and an enrichment of dipeptides, tripeptides, and oxo bile acids in VEO-IBD patients. Differential abundance analysis of the gut microbiome showed lower abundance of beneficial bacteria such as Bifidobacterium and Blautia, and higher abundance of Lachnospira, Veillonella, and Bacteroides in VEO-IBD. The joint analysis suggested a clear association between the altered gut microbiome composition and metabolic dysregulation, specifically for the N-acyl lipids. ConclusionsThis study offers unique insight into fecal microbial and metabolic signatures in VEO-IBD, paving the way for a better understanding of disease patterns and thereby more effective treatment strategies.

microbiology↗

bioRxiv2022

An untargeted metabolomics analysis of exogenous chemicals in human milk and transfer to the infant

Human milk is the optimal infant nutrition. However, while human-derived metabolites such as lipids and oligosaccharides in human milk are regularly reported, the presence of exogenous chemicals (such as drugs, food, and synthetic compounds) are often not addressed. To understand the types of exogenous compounds that might be present, human milk (n=996) was analyzed by untargeted metabolomics. This analysis revealed that lifestyle molecules such as medications and their metabolites, food, industrial sources such as plasticizers, cosmetics, microbial molecules, and other personal care products are found in human milk. We provide further evidence that some of these lifestyle molecules are also detectable in the newborns stool. Thus, this study gives important insight into the types of exposures infants receiving human milk might ingest due to the lifestyle choices, exposure, or medical status of the lactating parent.

pharmacology and toxicology↗

bioRxiv2021

Non-Invasive Skin Sampling Detects Systemically Administered Drugs in Humans

Clinical testing typically relies on invasive blood draws and biopsies. Alternative methods of sample collection are continually being developed to improve patient experience; swabbing the skin is one of the least invasive sampling methods possible. To show that skin swabs in combination with untargeted mass spectrometry (metabolomics) can be used for non-invasive monitoring of an oral drug, we report the kinetics and metabolism of diphenhydramine in healthy volunteers (n=10) over the course of 24 hours in blood and three regions of the skin. Diphenhydramine and its metabolites were observed on the skin after peak plasma levels, varying by compound and skin location, and is an illustrative example of how systemically administered molecules can be detected on the skin surface. The observation of diphenhydramine directly from the skin supports the hypothesis that both parent drug and metabolites can be qualitatively measured from a simple non-invasive swab of the skin surface. The mechanism of the drug and metabolites pathway to the skins surface remains unknown.

pharmacology and toxicology↗

bioRxiv2021

Physicochemical and Pharmacokinetic Properties Determining Drug Detection in Skin

Chemicals, including some systemically administered xenobiotics and their biotransformations, can be detected noninvasively using skin swabs and untargeted metabolomics analysis. We sought to understand the principal drivers that determine whether a drug taken orally or systemically is likely to be observed on the epidermis by using a random forest classifier to predict which drugs would be detected on the skin. A variety of molecular descriptors describing calculated properties of drugs, such as measures of volume, electronegativity, bond energy, and electrotopology, were used to train the classifier. The mean area under the ROC curve was 0.71 for predicting drug detection on the epidermis, and the SHapley Additive exPlanations model interpretation technique was used to determine the most relevant molecular descriptors. Based on the analysis of 2,561 FDA approved drugs, we predict that therapeutic drug classes such as nervous system drugs are more likely to be detected on the skin. Detecting drugs and other chemicals noninvasively on the skin using untargeted metabolomics could be a useful clinical advancement in therapeutic drug monitoring, adherence, and health status.

bioinformatics↗