Project description:Background: Farm exposures in early life reduce the risks for childhood allergic diseases and asthma. There is less information about how farm exposures relate to respiratory illnesses and mucosal immune development. Objective: We hypothesized that children raised in farm environments have a lower incidence of viral illnesses over the first two years of life than non-farm children. We also analyzed between farm exposures or respiratory illnesses were related to patterns of nasal cell gene expression. Methods: The Wisconsin Infant Study Cohort (WISC) birth cohort enrolled farm and non-farm pregnant women from central Wisconsin. Parents reported prenatal farm and other environmental exposures. Illness frequency and severity were assessed using illness diaries and periodic surveys. Nasopharyngeal cell gene expression at age two years was compared to farm exposure and respiratory illness history. Results: There was a higher rate of respiratory illnesses in the non-farm vs. farm group (rate ratio 0.82 [0.69,0.97], p=0.020), but no significant differences in wheezing illnesses. There was a stepwise reduction in rates of respiratory illnesses in children exposed at least weekly to 0, 1, or ≥2 animals (p=0.006). In analyzing nasal cell gene expression, farm exposures and preceding respiratory illnesses were positively related to gene signatures for mononuclear cells and innate and antimicrobial responses. Conclusions: Children exposed to farms and farm animals had lower rates of respiratory illnesses over the first two years of life. Both farm exposures and preceding respiratory illnesses were associated with increased innate immune responses, suggesting that these exposures stimulate mucosal immune responses to reduce subsequent illness frequency.
Project description:Gut plasmids show heightened sensitivity to gut microenvironmental changes compared to their bacterial hosts. To explore their significance in colorectal cancer (CRC), we analyzed metagenomic data from 863 participants (312 CRC, 387 high-risk, 164 low-risk). Plasmid and bacterial profiles were characterized, along with trace elements and metabolites. Differential analysis, functional gene assessment (ARG, MGE, MRG, VFGB), random forest modeling, and structural equation modeling (SEM) were applied. In terms of overall abundance, plasmids in both the high-risk and CRC groups exhibited a decreasing trend. Gut plasmids significantly influenced the functional genes (ARG, MGE, MRG, VFGB) of their bacterial hosts. Six key bacterial hosts (Enterobacterales, Burkholderiales, Hyphomicrobiales, Lactobacillales, Bacteroidales, Campylobacterales) and 12 plasmid markers were identified. The plasmid-based model effectively predicted CRC risk. SEM revealed that trace elements (e.g., Ni), metabolites (e.g., 5-Hydroxytryptophol), and host bacteria (e.g., Campylobacterales, Enterobacterales) predominantly exerted negative effects on most plasmids, whereas Ni exhibited a positive influence on plasmids NZ_CP013564.1, NZ_CP024312.1, and NZ_CP48284.1. We characterized the composition of gut plasmids and their bacterial hosts, explored the impacts of gut plasmids on bacterial functionality, and mapped multi-omics interaction networks linking plasmids, hosts, and metabolic features.