Kirandeep K. Gill

Background: Early life is a critical period in which the gut microbiome and the enteric nervous system (ENS) develop together, shaping long‐term gastrointestinal (GI) function. Human milk feeding and particularly maternal secretor phenotype strongly influence early microbiome composition. However, how human milk promoted microbiomes impact ENS development is still largely unknown. Methods: Male and female juvenile (three weeks old) C57BL/6 germ‐free mice were colonized with fecal microbiota from infants whose mothers were secretors (SMM, 2‐fucosyl lactose in milk) or non‐secretors (NSM) or from infants consuming cow's milk formula (MFM). Non‐transplanted male and female germ‐free mice served as controls. GI transit was assessed at post‐natal day 35‐37. ENS neuronal and glial organization was evaluated in full‐thickness colon preparations using immunohistochemistry and confocal microscopy. Key Results: Female germ‐free mice receiving SMM exhibited higher distal GI transit efficiency and a higher proportion of nitrergic neurons in the myenteric plexus compared to sex‐matched controls and to males. Choline acetyltransferase (ChAT; marker for excitatory cholinergic neurons) immunoreactivity was higher in the myenteric ganglia of germ‐free female compared to male mice. ChAT immunoreactivity increased in SMM and MFM males, while it was significantly reduced in NSM and MFM females compared to controls. Infant microbiomes did not affect myenteric glial cells, which were more abundant in males than females across all groups. Conclusions and Inferences: Our findings demonstrate that early‐life maternal secretor‐associated infant microbiomes exert sex‐specific effects on ENS neuronal phenotypes and GI motility, underlying a previously unrecognized link between infant‐derived microbiomes and ENS development that warrants investigation in larger cohorts.

Long-term exposures to low dose space radiation may have adverse effects on human health during missions in deep space. Conventional dosimetry, monitoring of prodromal symptoms, and peripheral lymphocyte counts are of limited value as biomarkers of organ- and tissue-specific radiation injury, particularly of injuries that appear weeks or months after radiation exposure. To assess the feasibility of using plasma metabolic and lipidomic profiles as biomarkers of injury from space radiation, we used a mouse model of exposure to low doses of oxygen ions (¹⁶O) and protons (¹H). Plasma profiles were compared with those of mice exposed to γ-rays as a reference set. Our results demonstrate major changes in glycerophospholipid metabolism, amino acid metabolism, as well as fatty acid metabolism. We also observed dyslipidemia and lipid peroxidation, suggesting an inflammatory phenotype with possible long-term consequences to overall health upon exposure to low doses of high linear energy transfer (LET) radiation.