Project description:Aging is associated with declining immunity and inflammation as well as alterations in the gut microbiome with a decrease of beneficial microbes and increase in pathogenic ones. The aim of this study was to investigate aging associated gut microbiome in relation to immunologic and metabolic profile in a non-human primate (NHP) model. 12 old (age>18 years) and 4 young (age 3-6 years) Rhesus macaques were included in this study. Immune cell subsets were characterized in PBMC by flow cytometry and plasma cytokines levels were determined by bead based multiplex cytokine analysis. Stool samples were collected by ileal loop and investigated for microbiome analysis by shotgun metagenomics. Serum, gut microbial lysate and microbe-free fecal extract were subjected to metabolomic analysis by mass-spectrometry. Our results showed that the old animals exhibited higher inflammatory biomarkers in plasma and lower CD4 T cells with altered distribution of naïve and memory T cell maturation subsets. The gut microbiome in old animals had higher abundance of Archaeal and Proteobacterial species and lower Firmicutes than the young. Significant enrichment of metabolites that contribute to inflammatory and cytotoxic pathways was observed in serum and feces of old animals compared to the young. We conclude that aging NHP undergo immunosenescence and age associated alterations in the gut microbiome that has a distinct metabolic profile.
Project description:Opioid analgesics are frequently prescribed in the United States and worldwide. However, serious side effects such as addiction, immunosuppression and gastrointestinal symptoms limit long term use. In the current study using a chronic morphine-murine model a longitudinal approach was undertaken to investigate the role of morphine modulation of gut microbiome as a mechanism contributing to the negative consequences associated with opioids use. The results revealed a significant shift in the gut microbiome and metabolome within 24 hours following morphine treatment when compared to placebo. Morphine induced gut microbial dysbiosis exhibited distinct characteristic signatures profiles including significant increase in communities associated with pathogenic function, decrease in communities associated with stress tolerance. Collectively, these results reveal opioids-induced distinct alteration of gut microbiome, may contribute to opioids-induced pathogenesis. Therapeutics directed at these targets may prolong the efficacy long term opioid use with fewer side effects.
Project description:A Gram-positive, aerobic, rod-shaped bacterium, designated as strain 1605-214T, was isolated from the blood sample of a patient with cholangitis. Based on its 16S rRNA gene sequence, the strain 1605-214T belonged to the genus Cohnella and exhibited 97.9% sequence identity with Cohnella luojiensis DSM 24270T (GQ214052). DNA-DNA hybridization, digital DNA-DNA hybridization, and average nucleotide identity values between the two species were 23% ± 1.9, 21.1%, and 77.2%, respectively. The cellular fatty acids of strain 1605-214T were mainly comprised of anteiso-C15:0 (36.1%), iso-C16:0 (16.5%), and C16:0 (15.1%). The predominant quinone was menaquinone-7; predominant polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, and aminophospholipid-1. The cell wall peptidoglycan of strain 1605-214T contained meso-diaminopimelic acid. DNA G + C content of strain 1605-214T was 50.6 mol%. 5187 genes out of a total of 5413 (94.6%) were assigned putative functions using eggNOG v5.0. Based on genotypic characteristics and genomic sequence analysis results, strain 1605-214T was confirmed to represent a novel species of genus Cohnella, for which the name Cohnella cholangitidis sp. nov., was proposed.
Project description:Flavonoids are stress-inducible metabolites important for plant-microbe interactions. In contrast to their well-known function in initiating rhizobia nodulation in legumes, it is unclear whether and how flavonoids may contribute to plant stress resistance through affecting non-nodulating bacteria in the root microbiome. Here we show how flavonoids preferentially attracts Aeromonadaceae in Arabidopsis thaliana root microbiome and how flavonoid-dependent recruitment of an Aeromona spp. results in enhanced plant Na_H1 resistance.
Project description:Flavonoids are stress-inducible metabolites important for plant-microbe interactions. In contrast to their well-known function in initiating rhizobia nodulation in legumes, it is unclear whether and how flavonoids may contribute to plant stress resistance through affecting non-nodulating bacteria in the root microbiome. Here we show how flavonoids preferentially attracts Aeromonadaceae in Arabidopsis thaliana root microbiome and how flavonoid-dependent recruitment of an Aeromona spp. results in enhanced plant drought resistance.
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.
Project description:Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut, but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals, reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids and the outgrowth of microorganisms capable of triggering inflammatory bowel disease. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles. RNA-Seq analysis of the human gut microbiome during consumption of a plant- or animal-based diet.