Biology subjects

Schell, L. D.

Publications and source records attributed to Schell, L. D..

4 recordsLinked to original sources

bioRxiv2026

Evolutionary trade-offs between growth and reproduction under obesogenic conditions: sex-biased skeletal and gonadal maturation in mice

Adolescence is a brief period during which finite energy resources are reallocated from linear growth toward reproductive maturation. Rising childhood obesity and earlier onset of puberty suggest that modern, energy rich diets may distort these evolved energy allocation rules, but causal mechanisms remain unclear. Here, we expose male and female wild-type and leptin receptor deficient (Db/Db) to either high fat or normal chow diets. We longitudinally analyze metabolic, skeletal, gonadal, endocrine and insulin-receptor phenotypes from 4-10 weeks of age (sexual maturation window in mice). In WT males, HFDs increased adiposity and impaired glucose tolerance, and selectively remodeled joint morphology, advanced gonadal maturation, and shifted insulin receptor expression from growth plates to testes. Together, these changes indicate a rebalancing of energy use toward reproduction at the expense of skeletal and metabolic health. WT females showed subtler systemic metabolic disruption but clear diet-responsive changes in growth plate and ovarian maturation. Our findings indicate that energy-rich diets during adolescence shift evolved allocation rules to prioritize reproductive readiness over skeletal robustness in a sex-dependent manner, with potential consequences for precocious puberty and bone health in humans.

evolutionary biology↗

bioRxiv2026

Fasting and re-feeding independently alter mouse gut microbiota during intermittent fasting

Intermittent fasting (IF) elicits metabolic benefits that are partially driven by the gut microbiome. Studies have focused on endpoint IF-induced changes in the gut microbiome but have not explored whether the oscillating nature of IF elicits day-to-day microbiome changes that could independently affect health. To discriminate the long-term and short-term effects of IF on the gut microbiota, we fasted mice every other day (IF1:1) or every two days (IF1:2), measuring daily changes in body mass and composition, food intake, and gut microbiota composition. We show that short-term effects of fasting and re-feeding on gut microbiota composition outweigh longer-term effects of IF treatment, with composition responding differently to re-feeding and fasting. Re-feeding specifically promoted rapid expansion of Lactobacillus, a bacterial genus linked mechanistically to the metabolic benefits of IF. Our results highlight the plasticity of the gut microbiota, especially re-feeding effects, as a potential contributor to microbiome-mediated metabolic benefits of IF.

microbiology↗

bioRxiv2025

Early-life microbiota disruption by antibiotics elicits fitness trade-offs that differ by sex

Exposure to early-life antibiotics (ELA) promotes adult obesity across diverse species, often more strongly in males than females1-3. However, the physiological and evolutionary mechanisms driving ELA-mediated developmental plasticity and their consequences for fitness remain unclear3. Here, treating young mice with high- or low-dose ampicillin altered the gut microbiome and elicited reduced lean mass and energy expenditure in males to promote increased adult visceral adiposity. High-dose ELA constrained energy availability during treatment, evidenced by reduced growth and cecal short-chain fatty acids, raising the possibility that developmental plasticity under ELA could be adaptive in energy-limited environments. Adult ELA-treated males had reduced fitness under free-fed conditions -- driven by smaller body size, fat stores, and impaired immunity -- but were buffered against fitness reductions under caloric restriction, consistent with predictive adaptive response models of development4,5. Strikingly, ELA-treated females exhibited none of the proximate metabolic responses observed in males, with adult body size and composition indistinguishable from controls. In the absence of similar developmental plasticity, ELA-treated females exhibited exacerbated fitness reductions under caloric restriction, including lower energetic investments in reproduction and immunity. Our results suggest that ELA exposure elicits sexually dimorphic developmental responses that engender long-term health and fitness consequences dependent on adult nutritional conditions.

evolutionary biology↗

bioRxiv2024

Dietary preservatives alter the gut microbiota in vitro and in vivo with sex-specific consequences for host metabolic development

Antibiotics in early life can promote adiposity via interactions with the gut microbiota. However, antibiotics represent only one possible route of antimicrobial exposure. Dietary preservatives exhibit antimicrobial activity, contain chemical structures accessible to microbial enzymes, and alter environmental conditions favoring specific microbial taxa. Therefore, preservatives that retain bioactivity in the gut might likewise alter the gut microbiota and host metabolism. Here we conduct in vitro, ex vivo, and in vivo experiments in mice to test the effects of preservatives on the gut microbiota and host physiology. We screened common dietary preservatives against a panel of human gut isolates and whole fecal communities, finding that preservatives strongly altered microbial growth and community structure. We exposed mice to diet-relevant doses of 4 preservatives [acetic acid, BHA (butylated hydroxyanisole), EDTA (ethylenediaminetetraacetic acid) and sodium sulfite], which each induced compound-specific changes in gut microbiota composition. Finally, we compared the long-term effects of early-life EDTA and low-dose antibiotic (ampicillin) exposure. EDTA exposure modestly reduced nutrient absorption and cecal acetate in both sexes, resulting in lower adiposity in females despite greater food intake. Females exposed to ampicillin also exhibited lower adiposity, along with larger brains and smaller livers. By contrast, in males, ampicillin exposure generally increased energy harvest and decreased energy expenditure, resulting in higher adiposity. Our results highlight the potential for everyday doses of common dietary preservatives to affect the gut microbiota and impact metabolism differently in males and females. Thus, despite their generally-regarded-as-safe designation, preservatives could have unintended consequences for consumer health. SIGNIFICANCEEarly-life exposure to antibiotics can alter the gut microbiota and shape adult metabolic health. Here we show that dietary preservatives can have analogous effects. Common dietary preservatives altered gut microbiota composition in vitro, ex vivo and in vivo. Early-life EDTA exposure had long-term, sex-specific consequences for energy metabolism. Simultaneously, we deliver new mechanistic understanding of early-life antimicrobial-induced effects on adiposity via evidence that low-dose ampicillin treatment increases energy harvest while conserving energy expenditure in males, promoting adiposity, while EDTA treatment dampens energy harvest, promoting leanness in females. Overall, our results emphasize that early-life gut microbiome disruptions can be triggered by diverse antimicrobial exposures, with previously unappreciated metabolic consequences that differ for males and females.

physiology↗