Electronic nicotine delivery systems (ENDS) or e-cigarettes have emerged as a popular recreational tool among adolescents and adults. Although the use of ENDS is often promoted as a safer alternative to conventional cigarettes, few comprehensive studies have assessed the long-term effects of vaporized nicotine and its associated solvents, propylene glycol (PG) and vegetable glycerin (VG). Here, we show that compared with smoke exposure, mice receiving ENDS vapor for 4 months failed to develop pulmonary inflammation or emphysema. However, ENDS exposure, independent of nicotine, altered lung lipid homeostasis in alveolar macrophages and epithelial cells. Comprehensive lipidomic and structural analyses of the lungs revealed aberrant phospholipids in alveolar macrophages and increased surfactant-associated phospholipids in the airway. In addition to ENDS-induced lipid deposition, chronic ENDS vapor exposure downregulated innate immunity against viral pathogens in resident macrophages. Moreover, independent of nicotine, ENDS-exposed mice infected with influenza demonstrated enhanced lung inflammation and tissue damage. Together, our findings reveal that chronic e-cigarette vapor aberrantly alters the physiology of lung epithelial cells and resident immune cells and promotes poor response to infectious challenge. Notably, alterations in lipid homeostasis and immune impairment are independent of nicotine, thereby warranting more extensive investigations of the vehicle solvents used in e-cigarettes.

Microbiota plays a critical role in the overall growth performance and health status of dairy cows, especially during their early life. Several studies have reported that fecal microbiome of neonatal calves is shifted by various factors such as diarrhea, antibiotic treatment, or environmental changes. Despite the importance of gut microbiome, a lack of knowledge regarding the composition and functions of microbiota impedes the development of new strategies for improving growth performance and disease resistance during the neonatal calf period. In this study, we utilized next-generation sequencing to monitor the time-dependent dynamics of the gut microbiota of dairy calves before weaning (1–8 weeks of age) and further investigated the microbiome changes caused by diarrhea. Metagenomic analysis revealed that continuous changes, including increasing gut microbiome diversity, occurred from 1 to 5 weeks of age. However, the composition and diversity of the fecal microbiome did not change after 6 weeks of age. The most prominent changes in the fecal microbiome composition caused by aging at family level were a decreased abundance of Bacteroidaceae and Enterobacteriaceae and an increased abundance of Prevotellaceae. Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) analysis indicated that the abundance of microbial genes associated with various metabolic pathways changed with aging. All calves with diarrhea symptoms showed drastic microbiome changes and about a week later returned to the microbiome of pre-diarrheal stage regardless of age. At phylum level, abundance of Bacteroidetes was decreased (p = 0.09) and that of Proteobacteria increased (p = 0.07) during diarrhea. PICRUSt analysis indicated that microbial metabolism-related genes, such as starch and sucrose metabolism, sphingolipid metabolism, alanine aspartate, and glutamate metabolism were significantly altered in diarrheal calves. Together, these results highlight the important implications of gut microbiota in gut metabolism and health status of neonatal dairy calves.

Owing to increasing global temperatures, heat stress is a major problem affecting dairy cows, and abnormal metabolic responses during heat stress likely influence dairy cow immunity. However, the mechanism of this crosstalk between metabolism and immunity during heat stress remains unclear. We used two representative dairy cow breeds, Holstein and Jersey, with distinct heat-resistance characteristics. To understand metabolic and immune responses to seasonal changes, normal environmental and high-heat environmental conditions, we assessed blood metabolites and immune cell populations. In biochemistry analysis from sera, we found that variety blood metabolites were decreased in both Holstein and Jersey cows by heat stress. We assessed changes in immune cell populations in peripheral blood mononuclear cells (PBMCs) using flow cytometry. There were breed-specific differences in immune-cell population changes. Heat stress only increased the proportion of B cells (CD4–CD21+) and heat stress tended to decrease the proportion of monocytes (CD11b+CD172a+) in Holstein cows. Our findings expand the understanding of the common and specific changes in metabolism and immune response of two dairy cow breeds under heat stress conditions.

The gastrointestinal tract contains multiple types of immune cells that maintain the balance between tolerance and activation at the first line of host defense facing non-self antigens, including dietary antigens, commensal bacteria, and sometimes unexpected pathogens. The maintenance of homeostasis at the gastrointestinal tract requires stringent regulation of immune responses against various environmental conditions. Dietary components can be converted into gut metabolites with unique functional activities through host as well as microbial enzymatic activities. Accumulating evidence demonstrates that gastrointestinal metabolites have significant impacts on the regulation of intestinal immunity and are further integrated into the immune response of distal mucosal tissue. Metabolites, especially those derived from the microbiota, regulate immune cell functions in various ways, including the recognition and activation of cell surface receptors, the control of gene expression by epigenetic regulation, and the integration of cellular metabolism. These mucosal immune regulations are key to understanding the mechanisms underlying the development of gastrointestinal disorders. Here, we review recent advancements in our understanding of the role of gut metabolites in the regulation of gastrointestinal immunity, highlighting the cellular and molecular regulatory mechanisms by macronutrient-derived metabolites.

Twenty weaned piglets with initial body weight of 6.83 ± 0.33 kg (21 day of age, LYD) were randomly assigned to four treatments for a two-week feeding trial to determine the effects of different dietary zinc on nutrient digestibility, intestinal health, and microbiome of weaned piglets. The dietary treatments included a negative control (CON), standard ZnO (ZnO, 2500 ppm), zinc chelate with glycine (Chelate-ZnO, 200 ppm), and nanoparticle-sized ZnO (Nano-ZnO, 200 ppm). At 0 to 1 week, the diarrhea score was decreased in the CON group compared with the ZnO, Chelate-ZnO, and Nano-ZnO group. In overall period, the ZnO and Nano-ZnO groups exhibited improved diarrhea scores compared to the CON group. The apparent total tract digestibility of dry matter and gross energy was the lowest in the CON group after one week. Compared to the ZnO group, the chelate-ZnO group exhibited higher proportion of T-bet+ and FoxP3+ T cells and the nano-ZnO group had higher numbers of RORgt+ and GATA3+ T cells in the mesenteric lymph nodes. ZnO group increased IL-6 and IL-8 levels in the colon tissues and these positive effects were observed in both chelate ZnO and nano-ZnO groups with lower level. The 16S rRNA gene analysis showed that the relative abundance of Prevotella was higher in the ZnO-treated groups than in the CON group and that of Succinivibrio was the highest in the nano-ZnO group. The relative abundance of Lactobacillus increased in the ZnO group. In conclusion, low nano-ZnO levels have similar effects on nutrient digestibility, fecal microflora, and intestinal immune profiles in weaning pigs; thus, nano-ZnO could be used as a ZnO alternative for promoting ZnO utilization and intestinal immunity.

The microbial community within the rumen can be changed and shaped by heat stress. Accumulating data have suggested that different breeds of dairy cows have differential heat stress resistance; however, the underlying mechanism by which nonanimal factors contribute to heat stress are yet to be understood. This study is designed to determine changes in the rumen microbiome of Holstein and Jersey cows to normal and heat stress conditions. Under heat stress conditions, Holstein cows had a significantly higher respiration rate than Jersey cows. Heat stress increased the rectal temperature of Holstein but not Jersey cows. In the Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis, Jersey cows had a significantly higher proportion of genes associated with energy metabolism in the normal condition than that with other treatments. Linear discriminant analysis effect size (LEfSe) results identified six taxa as distinguishing taxa between normal and heat stress conditions in Holstein cows; in Jersey cows, 29 such taxa were identified. Changes in the rumen bacterial taxa were more sensitive to heat stress in Jersey cows than in Holstein cows, suggesting that the rumen mechanism is different in both breeds in adapting to heat stress. Collectively, distinct changes in rumen bacterial taxa and functional gene abundance in Jersey cows may be associated with better adaptation ability to heat stress.