@article {329, title = {Genetic background influences the effect of thirdhand smoke exposure on anxiety and memory in Collaborative Cross mice.}, journal = {Sci Rep}, volume = {11}, year = {2021}, month = {2021 06 24}, pages = {13285}, abstract = {

Growing evidence indicates that thirdhand smoke (THS) exposure induces many adverse health effects. However, it is unclear how THS exposure affects behavior and how host genetic background modulates phenotypic changes. Here we used the Collaborative Cross (CC) mouse population-based model to assess behavioral alterations immediately after THS exposure from 4 to 9\ weeks of age. We first measured anxiety-like behavior in six strains using light/dark box combined with a custom multivariate mouse tracking system. We developed an anxiety risk scoring system based on anxiety-related traits and then evaluated the THS impact on them. THS exposure significantly decreased anxiety risk in CC019 (P = 0.002) and CC051 (P = 0.009), but increased anxiety risk in CC036 (P \< 0.001), while the other three strains did not show significant changes in anxiety-related traits. Such differences were driven by female mice for the six measures of anxiety-like behavior. Memory potential was measured in the same cohort of mice using the passive avoidance assay. Both THS-exposed male and female CC019 mice displayed significant memory loss compared to controls while no significant changes were found in the other five strains. This study provides strong evidence that THS exposure leads to strain-dependent changes in anxiety-like behavior and memory, suggesting that host genetic variations play a critical role in individual susceptibility to THS-induced effects.

}, keywords = {Animals, Anxiety, Collaborative Cross Mice, Female, Humans, Male, Memory, Risk Factors, Tobacco Smoke Pollution}, issn = {2045-2322}, doi = {10.1038/s41598-021-92702-1}, author = {He, Li and Wang, Pin and Schick, Suzyann F and Huang, Abel and Jacob, Peyton and Yang, Xu and Xia, Yankai and Snijders, Antoine M and Mao, Jian-Hua and Chang, Hang and Hang, Bo} } @article {325, title = {Host genetics and gut microbiota cooperatively contribute to azoxymethane-induced acute toxicity in Collaborative Cross mice.}, journal = {Arch Toxicol}, volume = {95}, year = {2021}, month = {2021 03}, pages = {949-958}, abstract = {

Azoxymethane (AOM) is a widely used carcinogen to study chemical-induced colorectal carcinogenesis and is an agent for studying fulminant hepatic failure. The inter-strain susceptibility to acute toxicity by AOM has been reported, but its association with host genetics or gut microbiota remains largely unexplored. Here a cohort of genetically diverse Collaborative Cross (CC) mice was used to assess the contribution of host genetics and the gut microbiome to AOM-induced acute toxicity. We observed variation in AOM-induced acute liver failure across CC strains. Quantitative trait loci (QTL) analysis revealed three chromosome regions significantly associated with AOM toxicity. Genes located within these QTL, including peroxisome proliferator-activated receptor alpha (Ppara), were enriched for enzyme activator and nucleoside-triphosphatase regulator activity. We further demonstrated that the protein level of PPARĪ± in liver tissues from sensitive strains was remarkably lower compared to levels in resistant strains, consistent with protective role of PPAR family in liver injury. We discovered that the abundance levels of gut microbial families Anaeroplasmataceae, Ruminococcaceae, Lactobacillaceae, Akkermansiaceae and Clostridiaceae were significantly higher in the sensitive strains\ compared to the resistant strains. Using a random forest classifier method, we determined that the relative abundance levels of these microbial families predicted AOM toxicity with the area under the receiver-operating curve (AUC) of 0.75. Combining the three genetic loci and five microbial families increased the predictive accuracy of AOM toxicity (AUC of 0.99). Moreover, we found that Ruminococcaceae and Lactobacillaceae acted as mediators between host genetics and AOM toxicity. In conclusion, this study shows that host genetics and specific microbiome members play a critical role in AOM-induced acute toxicity, which provides a framework for analysis of the health effects from environmental toxicants.

}, keywords = {Animals, Azoxymethane, Carcinogens, Chemical and Drug Induced Liver Injury, Collaborative Cross Mice, Gastrointestinal Microbiome, Liver Failure, Acute, Male, Mice, Quantitative Trait Loci, Species Specificity}, issn = {1432-0738}, doi = {10.1007/s00204-021-02972-x}, author = {Zhong, Chenhan and He, Li and Lee, Sun-Young and Chang, Hang and Zhang, Yuqing and Threadgill, David W and Yuan, Ying and Zhou, Fuling and Celniker, Susan E and Xia, Yankai and Snijders, Antoine M and Mao, Jian-Hua} } @article {328, title = {Thirdhand cigarette smoke leads to age-dependent and persistent alterations in the cecal microbiome of mice.}, journal = {Microbiologyopen}, volume = {10}, year = {2021}, month = {2021 06}, pages = {e1198}, abstract = {

The gut microbiome composition is influenced by many factors including environmental exposures. Here, we investigated the effect of thirdhand cigarette smoke (THS) and exposure age on gut microbiome diversity. C57BL/6 mice were exposed to THS at human exposure relevant levels for three weeks during three different life stages: postnatal (0-3\ weeks of age), pubescent (4-7\ weeks of age), and adult (9-12\ weeks of age), respectively. Cecal microbiome profiles were assessed at 17\ weeks of age by 16S rRNA gene sequencing. We found that age at THS exposure strongly influenced the cecal microbiome composition. Although postnatal THS exposure significantly influenced the microbial composition, pubescent and adulthood exposures only had minor effects. The microbiome of postnatally THS-exposed mice significantly increased several degradation pathways that regulate glycolysis and pyruvate decarboxylation, and significantly decreased coenzyme A biosynthesis and pyrimidine deoxyribonucleoside salvage. Our results indicate that mouse postnatal development is particularly susceptible to persistent THS exposure effects on the gut microbiome.

}, keywords = {Age Factors, Animals, Bacteria, Cecum, Environmental Exposure, Female, Gastrointestinal Microbiome, Humans, Male, Mice, Mice, Inbred C57BL, Smoke, Tobacco, Tobacco Smoke Pollution}, issn = {2045-8827}, doi = {10.1002/mbo3.1198}, author = {He, Li and Zhou, Yan-Xia and Zhang, Yuqing and Hang, Bo and Chang, Hang and Schick, Suzaynn F and Celniker, Susan E and Xia, Yankai and Snijders, Antoine M and Mao, Jian-Hua} }