Microbial taxonomic and functional shifts in adolescents with type 1 diabetes are associated with clinical and dietary factors.

BACKGROUND: Evidence indicates a link between the pathogenesis of type 1 diabetes (T1D) and the gut microbiome. However, the regulation of microbial metabolic pathways and the associations of bacterial species with dietary factors in T1D are largely unknown. We investigated whether microbial metagenomic signatures in adolescents with T1D are associated with clinical/dietary factors. METHODS: Adolescents with T1D (case) and healthy adolescents (control) were recruited, and microbiome profiling in participants' stool samples was performed using shotgun metagenomic sequencing. The bioBakery3 pipeline (Kneaddata, Metaphlan 4 and HUMAnN) was used to assign taxonomy and functional annotations. Clinical (HbA1c) and dietary information (3-day food record) were collected for conducting association analysis using Spearman's correlation. FINDINGS: Adolescents with T1D exhibited modest changes in taxonomic composition of gut microbiome. Nineteen microbial metabolic pathways were altered in T1D, including downregulation of biosynthesis of vitamins (B2/flavin, B7/biotin and B9/folate), enzyme cofactors (NAD+ and s-adenosyl methionine) and amino acids (aspartate, asparagine and lysine) with an upregulation in the fermentation pathways. Furthermore, bacterial species associated with dietary and clinical factors differed between healthy adolescents and adolescents with T1D. Supervised models modeling identified taxa predictive of T1D status, and the top features included Coprococcus and Streptococcus. INTERPRETATION: Our study provides new insight into the alteration of microbial and metabolic signatures in adolescents with T1D, suggesting that microbial biosynthesis of vitamins, enzyme cofactors and amino acids may be potentially altered in T1D. FUNDING: Research grants from NIH/NCCIH: R01AT010247 and USDA/NIFA: 2019-67017-29253; and Larry & Gail Miller Family Foundation Assistantship.

Maternal nutritional status modifies heat-associated growth restriction in women with chronic malnutrition.

Rapid changes in the global climate are deepening existing health disparities from resource scarcity and malnutrition. Rising ambient temperatures represent an imminent risk to pregnant women and infants. Both maternal malnutrition and heat stress during pregnancy contribute to poor fetal growth, the leading cause of diminished child development in low-resource settings. However, studies explicitly examining interactions between these two important environmental factors are lacking. We leveraged maternal and neonatal anthropometry data from a randomized controlled trial focused on improving preconception maternal nutrition (Women First Preconception Nutrition trial) conducted in Thatta, Pakistan, where both nutritional deficits and heat stress are prevalent. Multiple linear regression of ambient temperature and neonatal anthropometry at birth (n = 459) showed a negative association between daily maximal temperatures in the first trimester and Z-scores of birth length and head circumference. Placental mRNA-sequencing and protein analysis showed transcriptomic changes in protein translation, ribosomal proteins, and mTORC1 signaling components in term placenta exposed to excessive heat in the first trimester. Targeted metabolomic analysis indicated ambient temperature associated alterations in maternal circulation with decreases in choline concentrations. Notably, negative impacts of heat on birth length were in part mitigated in women randomized to comprehensive maternal nutritional supplementation before pregnancy suggesting potential interactions between heat stress and nutritional status of the mother. Collectively, the findings bridge critical gaps in our current understanding of how maternal nutrition may provide resilience against adverse effects of heat stress in pregnancy.