Mammalian species have co-evolved with intestinal microbial communities that can shape development and adapt to environmental changes, including antibiotic perturbation or nutrient flux. In humans, especially children, microbiota disruption is common, yet the dynamic microbiome recovery from early-life antibiotics is still uncharacterized. Here we use a mouse model mimicking pediatric antibiotic use and find that therapeutic-dose pulsed antibiotic treatment (PAT) with a beta-lactam or macrolide alters both host and microbiota development. Early-life PAT accelerates total mass and bone growth, and causes progressive changes in gut microbiome diversity, population structure, and metagenomic content, with microbiome effects dependent on the number of courses and class of antibiotic. Whereas control microbiota rapidly adapts to a change in diet, PAT slows the ecological progression, with delays lasting several months with previous macrolide exposure. This study identifies key markers of disturbance and recovery, which may help provide therapeutic targets for microbiota restoration following antibiotic treatment.
The early life microbiome plays important roles in host immunological and metabolic development. Because the incidence of type 1 diabetes (T1D) has been increasing substantially in recent decades, we hypothesized that early-life antibiotic use alters gut microbiota, which predisposes to disease. Using non-obese diabetic mice that are genetically susceptible to T1D, we examined the effects of exposure to either continuous low-dose antibiotics or pulsed therapeutic antibiotics (PAT) early in life, mimicking childhood exposures. We found that in mice receiving PAT, T1D incidence was significantly higher, and microbial community composition and structure differed compared with controls. In pre-diabetic male PAT mice, the intestinal lamina propria had lower Th17 and Treg proportions and intestinal SAA expression than in controls, suggesting key roles in transducing the altered microbiota signals. PAT affected microbial lipid metabolism and host cholesterol biosynthetic gene expression. These findings show that early-life antibiotic treatments alter the gut microbiota and its metabolic capacities, intestinal gene expression and T-cell populations, accelerating T1D onset in non-obese diabetic mice.
Substance use in pregnant and parenting persons is common, yet still underdiagnosed. Substance use disorder (SUD) is one of the most stigmatized and undertreated chronic medical conditions, and this is exacerbated in the perinatal period. Many providers are not sufficiently trained in screening or treatment for substance use, so gaps in care for this population persist. Punitive policies towards substance use in pregnancy have proliferated, lead to decreased prenatal care, do not improve birth outcomes, and disproportionately impact Black, Indigenous, and other families of color. We discuss the importance of understanding the unique barriers of pregnancy-capable persons and drug overdose as one of the leading causes of maternal death in the United States. We highlight the principles of care from the obstetrician-gynecologist perspective including care for the dyad, person-centered language, and current medical terminology. We then review treatment of the most common substances, discuss SUD during the birthing hospitalization, and highlight the high risk of mortality in the postpartum period.
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