Project description:Purpose: Next-generation transcriptome sequencing was done to understand host and eukaryotic microbiome changes in gene expression in association with defined insecticide selection pressures. The specific goal of this research was to understand whole-body physiological responses in German cockroaches and associated microbiota, at the metatranscriptome level, to defined insecticide selection pressures. Methods: We used the insecticide indoxacarb as the selecting insecticide, which is an important bait active ingredient for cockroach control. Six generations of selection with indoxacarb bait produced a strain with substantial (>20x) resistance relative to inbred control lines originating from the same parental stock. Results: Metatranscriptome sequencing revealed 1123 significantly differentially expressed genes in > two of three statistical models (81 upregulated and 1042 downregulated; FDR p<0.001; log2FC of +/- 1). The majority of upreglated genes were from the host cockroach while the majority of downregulated genes were from associated viruses and the eukaryotic microbiome. Conclusions: We show here significant impacts by insecticide selection on not only host stress-respnses like detoxification, but also on clearace of microbial parasites, pathogens, commensals and/or symbionts.
Project description:Exposure to dogs in early infancy has been shown to reduce the risk of childhood allergic disease development and dog-ownership is associated with a distinct house dust microbial exposure. Here we demonstrate, using murine models, that exposure of mice toM-BM- dog-associated house dust protects against ovalbumin or cockroach allergen mediated airway pathology. Protected animals exhibited significant reductions in the total number of airway T cells, down-regulation of Th2-related airway responses as well as mucin secretion. Following house dust exposure, the cecal microbiome of protected animals was extensively restructured with significant enrichment of, amongst others, Lactobacillus johnsonii. Supplementation of wild type animals with L. johnsonii protected them against both airway allergen challenge or infection with respiratory syncytial virus. L. johnsonii mediated protection wasM-BM- associated with significant reductions in the total number and proportion of activated CD11c+/CD11b+ and CD11c+/CD8+ cells, as well as significantly reduced airway Th2 cytokine expression. Our results reveal that exposure to dog-associated household dust results in protection against airway allergen challenge and a distinct GI microbiome composition. Moreover the study identifies L. johnsonii as a pivotal species within the gastrointestinal tract capable of influencing adaptive immunity at remote mucosal surfaces in a manner that is protective against a variety of respiratory insults. The G2 PhyloChip microarray platform (commercially available from Second Genome, Inc.) was used to profile cecal gut bacteria from 29 mice: 7 controls, 5 gavaged with dust from homes with pets, 5 gavaged with dust from homes with no pets, 4 CRA-challenged, 4 gavaged with L. johnsonii, and 4 gavaged with L. johnsonii prior to CRA challenge. The PhyloChip was also used to profile 1 house dust sample collected from a home with dogs
Project description:Exposure to dogs in early infancy has been shown to reduce the risk of childhood allergic disease development and dog-ownership is associated with a distinct house dust microbial exposure. Here we demonstrate, using murine models, that exposure of mice toM-BM- dog-associated house dust protects against ovalbumin or cockroach allergen mediated airway pathology. Protected animals exhibited significant reductions in the total number of airway T cells, down-regulation of Th2-related airway responses as well as mucin secretion. Following house dust exposure, the cecal microbiome of protected animals was extensively restructured with significant enrichment of, amongst others, Lactobacillus johnsonii. Supplementation of wild type animals with L. johnsonii protected them against both airway allergen challenge or infection with respiratory syncytial virus. L. johnsonii mediated protection wasM-BM- associated with significant reductions in the total number and proportion of activated CD11c+/CD11b+ and CD11c+/CD8+ cells, as well as significantly reduced airway Th2 cytokine expression. Our results reveal that exposure to dog-associated household dust results in protection against airway allergen challenge and a distinct GI microbiome composition. Moreover the study identifies L. johnsonii as a pivotal species within the gastrointestinal tract capable of influencing adaptive immunity at remote mucosal surfaces in a manner that is protective against a variety of respiratory insults. The G2 PhyloChip microarray platform (commercially available from Second Genome, Inc.) was used to profile cecal gut bacteria from 29 mice: 7 controls, 5 gavaged with dust from homes with pets, 5 gavaged with dust from homes with no pets, 4 CRA-challenged, 4 gavaged with L. johnsonii, and 4 gavaged with L. johnsonii prior to CRA challenge. The PhyloChip was also used to profile 1 house dust sample collected from a home with dogs
Project description:Exposure to dogs in early infancy has been shown to reduce the risk of childhood allergic disease development and dog-ownership is associated with a distinct house dust microbial exposure. Here we demonstrate, using murine models, that exposure of mice toM-BM- dog-associated house dust protects against ovalbumin or cockroach allergen mediated airway pathology. Protected animals exhibited significant reductions in the total number of airway T cells, down-regulation of Th2-related airway responses as well as mucin secretion. Following house dust exposure, the cecal microbiome of protected animals was extensively restructured with significant enrichment of, amongst others, Lactobacillus johnsonii. Supplementation of wild type animals with L. johnsonii protected them against both airway allergen challenge or infection with respiratory syncytial virus. L. johnsonii mediated protection wasM-BM- associated with significant reductions in the total number and proportion of activated CD11c+/CD11b+ and CD11c+/CD8+ cells, as well as significantly reduced airway Th2 cytokine expression. Our results reveal that exposure to dog-associated household dust results in protection against airway allergen challenge and a distinct GI microbiome composition. Moreover the study identifies L. johnsonii as a pivotal species within the gastrointestinal tract capable of influencing adaptive immunity at remote mucosal surfaces in a manner that is protective against a variety of respiratory insults. The G2 PhyloChip microarray platform (commercially available from Second Genome, Inc.) was used to profile cecal gut bacteria from 29 mice: 7 controls, 5 gavaged with dust from homes with pets, 5 gavaged with dust from homes with no pets, 4 CRA-challenged, 4 gavaged with L. johnsonii, and 4 gavaged with L. johnsonii prior to CRA challenge. The PhyloChip was also used to profile 1 house dust sample collected from a home with dogs
Project description:Exposure to dogs in early infancy has been shown to reduce the risk of childhood allergic disease development and dog-ownership is associated with a distinct house dust microbial exposure. Here we demonstrate, using murine models, that exposure of mice to dog-associated house dust protects against ovalbumin or cockroach allergen mediated airway pathology. Protected animals exhibited significant reductions in the total number of airway T cells, down-regulation of Th2-related airway responses as well as mucin secretion. Following house dust exposure, the cecal microbiome of protected animals was extensively restructured with significant enrichment of, amongst others, Lactobacillus johnsonii. Supplementation of wild type animals with L. johnsonii protected them against both airway allergen challenge or infection with respiratory syncytial virus. L. johnsonii mediated protection was associated with significant reductions in the total number and proportion of activated CD11c+/CD11b+ and CD11c+/CD8+ cells, as well as significantly reduced airway Th2 cytokine expression. Our results reveal that exposure to dog-associated household dust results in protection against airway allergen challenge and a distinct GI microbiome composition. Moreover the study identifies L. johnsonii as a pivotal species within the gastrointestinal tract capable of influencing adaptive immunity at remote mucosal surfaces in a manner that is protective against a variety of respiratory insults.
Project description:Exposure to dogs in early infancy has been shown to reduce the risk of childhood allergic disease development and dog-ownership is associated with a distinct house dust microbial exposure. Here we demonstrate, using murine models, that exposure of mice to dog-associated house dust protects against ovalbumin or cockroach allergen mediated airway pathology. Protected animals exhibited significant reductions in the total number of airway T cells, down-regulation of Th2-related airway responses as well as mucin secretion. Following house dust exposure, the cecal microbiome of protected animals was extensively restructured with significant enrichment of, amongst others, Lactobacillus johnsonii. Supplementation of wild type animals with L. johnsonii protected them against both airway allergen challenge or infection with respiratory syncytial virus. L. johnsonii mediated protection was associated with significant reductions in the total number and proportion of activated CD11c+/CD11b+ and CD11c+/CD8+ cells, as well as significantly reduced airway Th2 cytokine expression. Our results reveal that exposure to dog-associated household dust results in protection against airway allergen challenge and a distinct GI microbiome composition. Moreover the study identifies L. johnsonii as a pivotal species within the gastrointestinal tract capable of influencing adaptive immunity at remote mucosal surfaces in a manner that is protective against a variety of respiratory insults.
Project description:Exposure to dogs in early infancy has been shown to reduce the risk of childhood allergic disease development and dog-ownership is associated with a distinct house dust microbial exposure. Here we demonstrate, using murine models, that exposure of mice to dog-associated house dust protects against ovalbumin or cockroach allergen mediated airway pathology. Protected animals exhibited significant reductions in the total number of airway T cells, down-regulation of Th2-related airway responses as well as mucin secretion. Following house dust exposure, the cecal microbiome of protected animals was extensively restructured with significant enrichment of, amongst others, Lactobacillus johnsonii. Supplementation of wild type animals with L. johnsonii protected them against both airway allergen challenge or infection with respiratory syncytial virus. L. johnsonii mediated protection was associated with significant reductions in the total number and proportion of activated CD11c+/CD11b+ and CD11c+/CD8+ cells, as well as significantly reduced airway Th2 cytokine expression. Our results reveal that exposure to dog-associated household dust results in protection against airway allergen challenge and a distinct GI microbiome composition. Moreover the study identifies L. johnsonii as a pivotal species within the gastrointestinal tract capable of influencing adaptive immunity at remote mucosal surfaces in a manner that is protective against a variety of respiratory insults.
Project description:Pancreatic cancer is the 3rd most prevalent cause of cancer related deaths in United states alone, with over 55000 patients being diagnosed in 2019 alone and nearly as many succumbing to it. Late detection, lack of effective therapy and poor understanding of pancreatic cancer systemically contributes to its poor survival statistics. Obesity and high caloric intake linked co-morbidities like type 2 diabetes (T2D) have been attributed as being risk factors for a number of cancers including pancreatic cancer. Studies on gut microbiome has shown that lifestyle factors as well as diet has a huge effect on the microbial flora of the gut. Further, modulation of gut microbiome has been seen to contribute to effects of intensive insulin therapy in mice on high fat diet. In another study, abnormal gut microbiota was reported to contribute to development of diabetes in Db/Db mice. Recent studies indicate that microbiome and microbial dysbiosis plays a role in not only the onset of disease but also in its outcome. In colorectal cancer, Fusobacterium has been reported to promote therapy resistance. Certain intra-tumoral bacteria have also been shown to elicit chemo-resistance by metabolizing anti-cancerous agents. In pancreatic cancer, studies on altered gut microbiome have been relatively recent. Microbial dysbiosis has been observed to be associated with pancreatic tumor progression. Modulation of microbiome has been shown to affect response to anti-PD1 therapy in this disease as well. However, most of the studies in pancreatic cancer and microbiome have remained focused om immune modulation. In the current study, we observed that in a T2D mouse model, the microbiome changed significantly as the hyperglycemia developed in these animals. Our results further showed that, tumors implanted in the T2D mice responded poorly to Gemcitabine/Paclitaxel (Gem/Pac) standard of care compared to those in the control group. A metabolomic reconstruction of the WGS of the gut microbiota further revealed that an enrichment of bacterial population involved in drug metabolism in the T2D group.