@article{ball_monte_aidara-kane_matheu_ru_thakur_ejobi_fedorka-cray_2020, title={International lineages of Salmonella enterica serovars isolated from chicken farms, Wakiso District, Uganda}, volume={15}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0220484}, DOI={10.1371/journal.pone.0220484}, abstractNote={The growing occurrence of multidrug-resistant (MDR) Salmonella enterica in poultry has been reported with public health concern worldwide. We reported, recently, the occurrence of Escherichia coli and Salmonella enterica serovars carrying clinically relevant resistance genes in dairy cattle farms in the Wakiso District, Uganda, highlighting an urgent need to monitor food-producing animal environments. Here, we present the prevalence, antimicrobial resistance, and sequence type of 51 Salmonella isolates recovered from 400 environmental samples from chicken farms in Uganda. Among the Salmonella isolates, 32/51 (62.7%) were resistant to at least one antimicrobial, and 10/51 (19.6%) displayed multiple drug resistance. Through PCR, five replicon plasmids were identified among all chicken Salmonella including IncFIIS 17/51 (33.3%), IncI1α 12/51 (23.5%), IncP 8/51 (15.7%), IncX1 8/51 (15.7%), and IncX2 1/51 (2.0%). In addition, we identified replicons through WGS (ColpVC and IncFIB). A significant seasonal difference between chicken sampling periods was observed (p= 0.0017). We conclude that MDR Salmonella highlights the risks posed to the animals, environment, and humans for infection. Implementing a robust integrated surveillance system in Uganda will help monitor MDR to help control infectious threats.}, number={1}, journal={PLOS ONE}, publisher={Public Library of Science (PLoS)}, author={Ball, Takiyah and Monte, Daniel and Aidara-Kane, Awa and Matheu, Jorge and Ru, Hongyu and Thakur, Siddhartha and Ejobi, Francis and Fedorka-Cray, Paula}, editor={Gao, FengEditor}, year={2020}, month={Jan}, pages={e0220484} } @article{tu_bian_chi_xue_gao_lai_ru_lu_2020, title={Metabolite Profiling of the Gut Microbiome in Mice with Dietary Administration of Black Raspberries}, volume={5}, ISSN={["2470-1343"]}, DOI={10.1021/acsomega.9b00237}, abstractNote={Mounting evidence has linked gut microbiome to health benefits of various functional foods. We previously reported that administration of a diet rich in black raspberry (BRB) changed the composition and diverse functional pathways in the mouse gut microbiome. To further characterize the functional profile in the gut microbiome of mice on BRB diet, in this follow-up study, we examined the metabolome differences in the gut microbiome driven by BRB consumption via targeted and untargeted metabolomic approaches. A distinct metabolite profile was observed in the gut microbiome of the mice on BRB diet, likely resulting from a combination of microbiome functional changes and unique precursors in BRBs. A number of functional metabolites, such as tetrahydrobiopterin and butyrate that were significantly increased in the gut microbiome may be linked to the beneficial health effects of BRB consumption. These findings suggest the important role of the gut microbiome in the health effects of BRBs and provide a connection among the health benefits of functional foods and the gut microbiome.}, number={3}, journal={ACS OMEGA}, author={Tu, Pengcheng and Bian, Xiaoming and Chi, Liang and Xue, Jingchuan and Gao, Bei and Lai, Yunjia and Ru, Hongyu and Lu, Kun}, year={2020}, month={Jan}, pages={1318–1325} } @article{zibura_posner_ru_westermeyer_2020, title={A preoperative bupivacaine retrobulbar block offers superior antinociception compared with an intraoperative splash block in dogs undergoing enucleation}, volume={23}, ISSN={["1463-5224"]}, DOI={10.1111/vop.12708}, abstractNote={AbstractPurposeInvestigate nociception differences in dogs undergoing enucleation administered bupivacaine either via preoperative retrobulbar block (pRB) or intraoperative splash block (iSB).MethodsProspective, randomized, double‐masked, clinical comparison study. Dogs undergoing unilateral enucleation were randomized to two groups: one received bupivacaine pRB and saline iSB of the same volume, and the other received saline pRB and bupivacaine iSB. The following intraoperative parameters were recorded: heart rate (HR), respiratory rate (RR), end‐tidal CO2 (EtCO2); systolic, mean, and diastolic arterial blood pressure (SAP, MAP, and DAP respectively); inspired end‐tidal isoflurane concentration (EtISOIns), and expired end‐tidal isoflurane concentration (EtISOExp). Pain scores were recorded pre‐ and postoperatively. Analgesic rescue was documented. Surgical hemorrhage and postoperative bruising and swelling were graded subjectively by the surgeon (HDW) and study coordinator (AEZ).ResultsA significant (P = .0399) increase from baseline in overall mean heart rate was recorded in iSB bupivacaine patients (n = 11) compared with pRB bupivacaine patients (n = 11), with no significant differences in other intraoperative physiologic parameters, or pain scores. More analgesic rescue events occurred in iSB bupivacaine patients compared to pRB bupivacaine patients. A near‐significant increase in intraoperative bleeding (P = .0519), and a significant increase in bruising (P = .0382) and swelling (P = .0223) was noted in the iSB bupivacaine group.ConclusionsPreoperative retrobulbar block bupivacaine is more effective than an iSB bupivacaine at controlling both intraoperative and postoperative nociception in dogs undergoing enucleation. Additionally, iSB causes more postoperative bruising and swelling and may be associated with increased intraoperative hemorrhage.}, number={2}, journal={VETERINARY OPHTHALMOLOGY}, author={Zibura, Ashley E. and Posner, Lysa P. and Ru, Hongyu and Westermeyer, Hans D.}, year={2020}, month={Mar}, pages={225–233} } @article{cone_lambeth_ru_fordham_piedrahita_spang_fisher_2019, title={Biomechanical Function and Size of the Anteromedial and Posterolateral Bundles of the ACL Change Differently with Skeletal Growth in the Pig Model}, volume={477}, ISSN={["1528-1132"]}, DOI={10.1097/CORR.0000000000000884}, abstractNote={ACL injuries are becoming increasingly common in children and adolescents, but little is known regarding age-specific ACL function in these patients. To improve our understanding of changes in musculoskeletal tissues during growth and given the limited availability of pediatric human cadaveric specimens, tissue structure and function can be assessed in large animal models, such as the pig.}, number={9}, journal={CLINICAL ORTHOPAEDICS AND RELATED RESEARCH}, author={Cone, Stephanie G. and Lambeth, Emily P. and Ru, Hongyu and Fordham, Lynn A. and Piedrahita, Jorge A. and Spang, Jeffrey T. and Fisher, Matthew B.}, year={2019}, month={Sep}, pages={2161–2174} } @article{chi_tu_liu_lai_xue_ru_lu_2019, title={Chronic Arsenic Exposure Induces Oxidative Stress and Perturbs Serum Lysolipids and Fecal Unsaturated Fatty Acid Metabolism}, volume={32}, ISSN={["1520-5010"]}, DOI={10.1021/acs.chemrestox.9b00039}, abstractNote={Chronic arsenic exposure from drinking water is a global public health issue, which is associated with numerous human diseases and influences millions of people worldwide. The effects of arsenic exposure to the metabolic networks remain elusive. Here, we exposed female C57BL/6J mice to 1 ppm inorganic arsenic in drinking water for 3 months to investigate how arsenic exposure perturbs serum and fecal metabolic profiles. We found decreased levels of serum compounds with antioxidative activities in arsenic-treated mice, in accordance with elevated oxidative stress indicated by higher urinary 8-oxo-2'-deoxyguanosine (8-oxo-dG) levels. Moreover, the levels of multiple lysophosphatidylcholines (lysoPCs) were significantly increased in the sera of arsenic-exposed mice, including lysoPC (O-18:0), lysoPC (20:3), lysoPC (18:1), and lysoPC (22:6). Arsenic exposure perturbed the levels of several key polyunsaturated fatty acids (PUFAs) in the fecal samples in concert with alterations in related microbial pathways. Additionally, changes in the abundances of many functional metabolites, together with decreased levels of amino acids, were found in the fecal samples of arsenic-treated mice. By delineating the impact of arsenic exposure on the metabolic profiles, the findings may provide new biomarkers and mechanistic insights into arsenic-associated diseases.}, number={6}, journal={CHEMICAL RESEARCH IN TOXICOLOGY}, author={Chi, Liang and Tu, Pengcheng and Liu, Chih-wei and Lai, Yunjia and Xue, Jingchuan and Ru, Hongyu and Lu, Kun}, year={2019}, month={Jun}, pages={1204–1211} } @article{dore_foster_ru_smith_2019, title={Comparison of oral, intravenous, and subcutaneous fluid therapy for resuscitation of calves with diarrhea}, volume={102}, ISSN={["1525-3198"]}, DOI={10.3168/jds.2019-16970}, abstractNote={ ABSTRACT Neonatal diarrhea remains the primary cause of mortality in dairy calves around the world, and optimal treatment protocols are needed. The main goals of therapy are to restore hydration and electrolyte concentrations, correct strong ion (metabolic) acidemia, and provide nutritional support. Administration of oral electrolyte solutions (OES) has long been the primary method used to treat neonatal diarrhea in humans and calves because OES are capable of addressing each of the primary goals of therapy. In calves with moderate dehydration, we hypothesized that oral electrolytes would be as good as or better than small volumes of intravenous (IV) or subcutaneous (SC) fluids. Therefore, the main goal of this study was to compare the ability of a commercially available oral electrolyte solution (OES) administered alone or in combination with hypertonic saline with small volumes of IV or SC fluid therapy to resuscitate calves with diarrhea. Thirty-three Holstein calves from 5 to 14 d of age were utilized in this clinical trial. Diarrhea and dehydration were induced by adding sucrose to the milk replacer. In addition, hydrochlorothiazide and spironolactone were given orally and furosemide intramuscularly. Depression status, clinical hydration scores, fecal consistency, and body weight were recorded at regular intervals. Treatment began when calves had severe diarrhea and had a decrease in plasma volume of at least 10%. Calves were randomly assigned to 1 of 4 treatment groups of 8 to 9 calves per group: (1) OES; (2) OES with hypertonic saline (4 mL/kg, IV); (3) IV fluids (lactated Ringer's, 2 L); or (4) SC fluids (lactated Ringer's, 2 L). Treatments were given at 0 and 12 h. Changes in plasma volume, blood pH, electrolyte levels, and physical examination scores were determined before therapy and again at 1, 2, 4, 8, and 12 h after each treatment. All 4 treatments were ultimately successful in improving hydration as well as increasing blood pH; however, animals in both groups that received OES had much faster resuscitation than those in either the IV or SC fluid group. In conclusion, oral electrolyte products remain the gold standard for resuscitating diarrheic calves with moderate dehydration and acidemia and will likely perform better than small volumes of IV lactated Ringer's solution. Subcutaneous fluids by themselves are a poor treatment option and should be only be used as supportive therapy following the initial correction of hypovolemia and metabolic acidosis. }, number={12}, journal={JOURNAL OF DAIRY SCIENCE}, author={Dore, V and Foster, D. M. and Ru, H. and Smith, G. W.}, year={2019}, month={Dec}, pages={11337–11348} } @article{oh_foster_williams_zheng_ru_lunn_mowat_2019, title={Diagnostic utility of clinical and laboratory test parameters for differentiating between sudden acquired retinal degeneration syndrome and pituitary‐dependent hyperadrenocorticism in dogs}, volume={22}, ISSN={1463-5216 1463-5224}, url={http://dx.doi.org/10.1111/vop.12661}, DOI={10.1111/vop.12661}, abstractNote={AbstractObjectiveTo identify discriminating factors, using clinical ophthalmic examination findings and routine laboratory testing, that differentiate dogs with early sudden acquired retinal degeneration (SARDS; vision loss <6 weeks’ duration), age‐ and breed‐matched control dogs, and dogs with pituitary‐dependent hyperadrenocorticism (PDH).AnimalsClient‐owned dogs: 15 with SARDS with <6 weeks duration of vision loss, 14 age‐ and breed‐matched control dogs, and 13 dogs with confirmed PDH.ProceduresDogs underwent ophthalmic examination, electroretinography (ERG) fundus photography, and spectral‐domain optical coherence tomography (SD‐OCT) in addition to physical examination, urinalysis, serum biochemistry, complete blood count, and adrenocorticotrophic hormone (ACTH) stimulation testing. Statistical analysis was performed using receiver operating curve area under the curve analysis, principal component analysis with sparse partial least squares analysis, and one‐way ANOVA.ResultsDogs with SARDS all had absent vision and ERG a‐ and b‐waves. SD‐OCT demonstrated that dogs with SARDS had significantly thicker inner retina, thinner outer nuclear layer, and thicker photoreceptor inner/outer segment measurements than either controls or dogs with PDH. Discriminating laboratory parameters between dogs with SARDS and PDH with high specificity included post‐ACTH serum cortisol (<19.3 μg/dL), AST:ALT ratio (>0.343), and urine specific gravity (>1.030).Conclusions and Clinical RelevanceWe have identified significant discriminators between SARDS and PDH. This work provides the basis for future studies that could identify and examine dogs with SARDS prior to vision loss, which may extend the potential therapeutic window for SARDS.}, number={6}, journal={Veterinary Ophthalmology}, publisher={Wiley}, author={Oh, Annie and Foster, Melanie L. and Williams, Jonathan G. and Zheng, Chaowen and Ru, Hongyu and Lunn, Katharine F. and Mowat, Freya M.}, year={2019}, month={Mar}, pages={842–858} } @article{tu_xue_bian_chi_gao_leng_ru_knobloch_weghorst_lu_2019, title={Dietary administration of black raspberries modulates arsenic biotransformation and reduces urinary 8-oxo-2 '-deoxyguanosine in mice}, volume={377}, ISSN={["1096-0333"]}, DOI={10.1016/j.taap.2019.114633}, abstractNote={Arsenic in drinking water is a worldwide public health problem due to its pathogenic induction of oxidative stress in various organ systems. Phytochemicals present in polyphenolic-rich fruits such as black raspberries (BRBs) have diverse health benefits, including antioxidation and modulation of enzymes in xenobiotic metabolism. We used a mouse model combined with a standardized BRB-rich diet to investigate the impact of BRB consumption on arsenic biotransformation. We observed a significant reduction of urinary 8-oxo-2'-deoxyguanosine (8-oxodG) together with elevated levels of methylation and urinary excretion of arsenic in mice concurrently fed BRBs upon arsenic exposure. Moreover, enzyme expression and liver metabolites involved in arsenic metabolism were found to be different between mice on BRB and control diets with arsenic exposure. These data indicate that BRB consumption affected arsenic biotransformation in vivo likely via alterations in related metabolic enzymes and cofactors, providing evidence on reduction of arsenic toxicity by consumption of BRBs.}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={Tu, Pengcheng and Xue, Jingchuan and Bian, Xiaoming and Chi, Liang and Gao, Bei and Leng, Jiapeng and Ru, Hongyu and Knobloch, Thomas J. and Weghorst, Christopher M. and Lu, Kun}, year={2019}, month={Aug} } @article{chi_lai_tu_liu_xue_ru_lu_2019, title={Lipid and Cholesterol Homeostasis after Arsenic Exposure and Antibiotic Treatment in Mice: Potential Role of the Microbiota}, volume={127}, ISSN={["1552-9924"]}, DOI={10.1289/EHP4415}, abstractNote={BACKGROUND Arsenic-induced liver X receptor/retinoid X receptor (LXR/RXR) signaling inhibition is a potential mechanism underlying the cardiovascular effects caused by arsenic. The gut microbiota can influence arsenic toxic effects. OBJECTIVE We aimed to explore whether gut microbiota play a role in arsenic-induced LXR/RXR signaling inhibition and the subsequent lipid and cholesterol dysbiosis. METHODS Conventional and antibiotic-treated mice (AB-treated mice) were exposed to 0.25 ppm and 1 ppm arsenic for 2 wk. Hepatic mRNAs were extracted and sequenced. The expression levels of genes associated with LXR/RXR signaling were quantified by quantitative real-time polymerase chain reaction (qPCR), and serum and hepatic cholesterol levels were measured. Liquid chromatography-mass spectrometry (LC-MS)-based lipidomics were used to examine serum and hepatic lipids. RESULTS Pathway analysis indicated that arsenic exposure differentially influenced the hepatic signaling pathways in conventional and AB-treated mice. The expression of sterol regulatory element-binding protein 1 (Srebp1c), 3-hydroxy-3-methylglutaryl-CoA reductase (Hmgcr), and cytochrome P450 family 7 subfamily A member 1 (Cyp7a1), as well as cholesterol efflux genes, including ATP binding cassette subfamily G member 5/8 (Abcg5/8) and cluster of differentiation 36 (Cd36), was lower in arsenic-exposed conventional mice but not in AB-treated mice. Similarly, under arsenic exposure, the hepatic expression of scavenger receptor class B member 1 (Scarb1), which is involved in reverse cholesterol transport (RCT), was lower in conventional mice, but was higher in AB-treated animals compared with controls. Correspondingly, arsenic exposure exerted opposite effects on the serum cholesterol levels in conventional and AB-treated mice, i.e., higher serum cholesterol levels in conventional mice but lower levels in AB-treated mice than in respective controls. Serum lipid levels, especially triglyceride (TG) levels, were higher in conventional mice exposed to 1 ppm arsenic, while arsenic exposure did not significantly affect the serum lipids in AB-treated mice. Liver lipid patterns were also differentially perturbed in a microbiota-dependent manner. CONCLUSIONS Our results suggest that in mice, the gut microbiota may be a critical factor regulating arsenic-induced LXR/RXR signaling perturbation, suggesting that modulation of the gut microbiota might be an intervention strategy to reduce the toxic effects of arsenic on lipid and cholesterol homeostasis. https://doi.org/10.1289/EHP4415.}, number={9}, journal={ENVIRONMENTAL HEALTH PERSPECTIVES}, author={Chi, Liang and Lai, Yunjia and Tu, Pengcheng and Liu, Chih-Wei and Xue, Jingchuan and Ru, Hongyu and Lu, Kun}, year={2019}, month={Sep} } @article{liu_chi_tu_xue_ru_lu_2019, title={Quantitative proteomics reveals systematic dysregulations of liver protein metabolism in sucralose-treated mice}, volume={196}, ISSN={["1876-7737"]}, DOI={10.1016/j.jprot.2019.01.011}, abstractNote={Sucralose, one kind of "sugar-free" artificial sweeteners, is widely used as food and drinks additives. It is generally considered that sucralose is safe because majority of ingested sucralose is not metabolized and absorbed by human body. However, increasing evidence shows the negative effects of artificial sweeteners in perturbations of gut microbiota which plays an important role in a variety of processes related to host health such as immune system development. Specifically, sucralose uptake can alter the homeostasis of mouse gut microbiota, resulting in the significant changes of gut bacterial genera diversity, metabolic patterns, and fecal metabolite profiles as well as inducing host liver inflammation. Therefore, there is a need to study liver proteome changes which may be potentially affected by sucralose-induced dysbiosis. In this study, isobaric labeling-based quantitative proteomics was performed to reveal the liver functional proteome changes in male C57BL/6J mice with sucralose administration in drinking water for six-month period. The labeled tryptic peptides were off-line fractionated before LC-MS/MS analysis to improve proteome coverage detected. SIGNIFICANCE: We demonstrated the first quantitative proteomics for mice liver proteome to evaluate the effect of sucralose consumption. In total, >5700 protein groups were identified from 18 mouse liver tissues (9 from control group; 9 from sucralose-treated group), and 4327 protein groups were quantified in all samples without any missing values. Among them, 113 protein groups were identified with statistical significance (q value <0.05) as differentially expressed proteins. Bioinformatics analysis revealed the systematic dysregulations of protein metabolism after sucralose treatment. Importantly, our findings proposed that enhanced inflammation may be triggered by ribosomal inactivation in sucralose treated mice liver.}, journal={JOURNAL OF PROTEOMICS}, author={Liu, Chih-Wei and Chi, Liang and Tu, Pengcheng and Xue, Jingchuan and Ru, Hongyu and Lu, Kun}, year={2019}, month={Mar}, pages={1–10} } @article{castel_olby_ru_mariani_muñana_early_2019, title={Risk factors associated with progressive myelomalacia in dogs with complete sensorimotor loss following intervertebral disc extrusion: a retrospective case-control study}, volume={15}, ISSN={1746-6148}, url={http://dx.doi.org/10.1186/s12917-019-2186-0}, DOI={10.1186/s12917-019-2186-0}, abstractNote={AbstractBackgroundProgressive myelomalacia (PMM) is a usually fatal complication of acute intervertebral disc extrusion (IVDE) in dogs but its risk factors are poorly understood. The objective of this retrospective case-control study was to identify risk factors for PMM by comparing dogs with complete sensorimotor loss following IVDE that did and did not develop the disease after surgery. We also investigated whether any risk factors for PMM influenced return of ambulation. Medical records of client-owned dogs with paraplegia and loss of pain perception that underwent surgery for IVDE from 1998 to 2016, were reviewed. Dogs were categorized as PMM yes or no based on clinical progression or histopathology. Walking outcome at 6 months was established. Signalment, onset and duration of signs (categorized), steroids, non-steroidal anti-inflammatory drugs (yes or no), site of IVDE (lumbar intumescence or thoracolumbar) and longitudinal extent of IVDE were retrieved and their associations with PMM and walking outcome were examined using logistic regression.ResultsOne hundred and ninety seven dogs were included, 45 with and 152 without PMM. A 6-month-outcome was available in 178 dogs (all 45 PMM dogs and 133 control dogs); 86 recovered walking (all in the control group). Disc extrusions at the lumbar intumescence were associated with PMM (p = 0.01, OR: 3.02, CI: 1.3–7.2). Surgery performed more than 12 h after loss of ambulation was associated with PMM (OR = 3.4; CI = 1.1–10.5,p = 0.03 for 12-24 h and OR = 4.6; CI = 1.3–16.6,p = 0.02 for the > 24 h categories when compared with the ≤12 h category). Treatment with corticosteroids was negatively associated with PMM (OR: 3.1; CI: 1.3–7.6,p = 0.01). The only variable to affect walking outcome was longitudinal extent of IVDE (OR = 2.6; CI = 1.3–5.3,p = 0.006).ConclusionDogs with lumbar intumescence IVDE are at increased risk of PMM. Timing of surgery and corticosteroid use warrant further investigations. PMM and recovery of walking are influenced by different factors.}, number={1}, journal={BMC Veterinary Research}, publisher={Springer Science and Business Media LLC}, author={Castel, Aude and Olby, Natasha J. and Ru, Hongyu and Mariani, Christopher L. and Muñana, Karen R. and Early, Peter J.}, year={2019}, month={Dec} } @article{lai_xue_liu_gao_chi_tu_lu_ru_2019, title={Serum Metabolomics Identifies Altered Bioenergetics, Signaling Cascades in Parallel with Exposome Markers in Crohn's Disease}, volume={24}, ISSN={["1420-3049"]}, DOI={10.3390/molecules24030449}, abstractNote={: Inflammatory bowel disease (IBD) has stimulated much interest due to its surging incidences and health impacts in the U.S. and worldwide. However, the exact cause of IBD remains incompletely understood, and biomarker is lacking towards early diagnostics and effective therapy assessment. To tackle these, the emerging high-resolution mass spectrometry (HRMS)-based metabolomics shows promise. Here, we conducted a pilot untargeted LC/MS metabolomic profiling in Crohn’s disease, for which serum samples of both active and inactive cases were collected, extracted, and profiled by a state-of-the-art compound identification workflow. Results show a distinct metabolic profile of Crohn’s from control, with most metabolites downregulated. The identified compounds are structurally diverse, pointing to important pathway perturbations ranging from energy metabolism (e.g., β-oxidation of fatty acids) to signaling cascades of lipids (e.g., DHA) and amino acid (e.g., L-tryptophan). Importantly, an integral role of gut microbiota in the pathogenesis of Crohn’s disease is highlighted. Xenobiotics and their biotransformants were widely detected, calling for massive exposomic profiling for future cohort studies as such. This study endorses the analytical capacity of untargeted metabolomics for biomarker development, cohort stratification, and mechanistic interpretation; the findings might be valuable for advancing biomarker research and etiologic inquiry in IBD.}, number={3}, journal={MOLECULES}, author={Lai, Yunjia and Xue, Jingchuan and Liu, Chih-Wei and Gao, Bei and Chi, Liang and Tu, Pengcheng and Lu, Kun and Ru, Hongyu}, year={2019}, month={Feb} } @article{xue_lai_chi_tu_leng_liu_ru_lu_2019, title={Serum Metabolomics Reveals That Gut Microbiome Perturbation Mediates Metabolic Disruption Induced by Arsenic Exposure in Mice}, volume={18}, ISSN={["1535-3907"]}, DOI={10.1021/acs.jproteome.8b00697}, abstractNote={Arsenic contamination in drinking water has been a worldwide health concern for decades. In addition to being a well-recognized carcinogen, arsenic exposure has also been linked to diabetes, neurological effects, and cardiovascular diseases. Recently, increasing evidence has indicated that gut microbiome is an important risk factor in modulating the development of diseases. We aim to investigate the role of gut microbiome perturbation in arsenic-induced diseases by coupling a mass-spectrometry-based metabolomics approach and an animal model with altered gut microbiome induced by bacterial infection. Serum metabolic profiling has revealed that gut microbiome perturbation and arsenic exposure induced the dramatic changes of numerous metabolite pathways, including fatty acid metabolism, phospholipids, sphingolipids, cholesterols, and tryptophan metabolism, which were not or were less disrupted when the gut microbiome stayed normal. In summary, this study suggests that gut microbiome perturbation can exacerbate or cause metabolic disorders induced by arsenic exposure.}, number={3}, journal={JOURNAL OF PROTEOME RESEARCH}, author={Xue, Jingchuan and Lai, Yunjia and Chi, Liang and Tu, Pengcheng and Leng, Jiapeng and Liu, Chih-Wei and Ru, Hongyu and Lu, Kun}, year={2019}, month={Mar}, pages={1006–1018} } @article{gilbert_langenbach_marcellin-little_pease_ru_2019, title={Stifle joint osteoarthritis at the time of diagnosis of cranial cruciate ligament injury is higher in Boxers and in dogs weighing more than 35 kilograms}, volume={60}, ISSN={["1740-8261"]}, DOI={10.1111/vru.12718}, abstractNote={AbstractOsteoarthritis is a ubiquitous disease in dogs. The purpose of this retrospective study was to characterize the severity and distribution of osteoarthritis (OA) within the joint and to identify differences among dog breeds in the severity of OA in the cranial cruciate ligament (CCL)‐deficient stifle joint. Radiographs of 240 stifles from 51 Boxers, 66 German Shepherds, 100 Labrador Retrievers, and 23 Siberian Huskies with confirmed CCL rupture were included. Radiographs of the stifle joint were evaluated and OA severity was graded at 33 sites within and around the joint, and patella alta was graded as present or absent for a potential total stifle OA score of 100. Osteophyte size was correlated to OA severity score. Total OA scores were calculated and compared within and between breeds globally as well as at each joint site. Dogs weighing >35 kg had a higher total OA score than those weighing <35 kg. Osteoarthritis scores were highest at the apical patella, proximolateral tibia, and sesamoid bones, corresponding to the proximal, lateral, and caudal aspects of the joint, respectively. No statistically significant differences were found among the mean OA scores of various stifle joint regions. Boxer dogs had a higher total OA score than other breeds. We concluded that dogs have a consistent distribution pattern of OA within the stifle joint after CCL injury. Radiographic OA is more severe in the proximal, lateral, and caudal aspects of the joint. Boxers had more severe OA than the other breeds evaluated in the study.}, number={3}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Gilbert, Samuel and Langenbach, Anke and Marcellin-Little, Denis J. and Pease, Anthony P. and Ru, Hongyu}, year={2019}, pages={280–288} } @article{cone_piercy_lambeth_ru_piedrahita_spang_fordham_fisher_2019, title={Tissue-specific changes in size and shape of the ligaments and tendons of the porcine knee during post-natal growth}, volume={14}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0219637}, abstractNote={Prior studies have analyzed growth of musculoskeletal tissues between species or across body segments; however, little research has assessed the differences in similar tissues within a single joint. Here we studied changes in the length and cross-sectional area of four ligaments and tendons, (anterior cruciate ligament, patellar tendon, medial collateral ligament, lateral collateral ligament) in the tibiofemoral joint of female Yorkshire pigs through high-field magnetic resonance imaging throughout growth. Tissue lengths increased by 4-to 5-fold from birth to late adolescence across the tissues while tissue cross-sectional area increased by 10-20-fold. The anterior cruciate ligament and lateral collateral ligament showed allometric growth favoring change in length over change in cross-sectional area while the patellar tendon and medial collateral ligament grow in an isometric manner. Additionally, changes in the length and cross-sectional area of the anterior cruciate ligament did not increase as much as in the other ligaments and tendon of interest. Overall, these findings suggest that musculoskeletal soft tissue morphometry can vary within tissues of similar structure and within a single joint during post-natal growth.}, number={10}, journal={PLOS ONE}, author={Cone, Stephanie G. and Piercy, Hope E. and Lambeth, Emily P. and Ru, Hongyu and Piedrahita, Jorge A. and Spang, Jeffrey T. and Fordham, Lynn A. and Fisher, Matthew B.}, year={2019}, month={Oct} } @misc{xue_lai_liu_ru_2019, title={Towards Mass Spectrometry-Based Chemical Exposome: Current Approaches, Challenges, and Future Directions}, volume={7}, ISSN={["2305-6304"]}, DOI={10.3390/toxics7030041}, abstractNote={The proposal of the “exposome” concept represents a shift of the research paradigm in studying exposure-disease relationships from an isolated and partial way to a systematic and agnostic approach. Nevertheless, exposome implementation is facing a variety of challenges including measurement techniques and data analysis. Here we focus on the chemical exposome, which refers to the mixtures of chemical pollutants people are exposed to from embryo onwards. We review the current chemical exposome measurement approaches with a focus on those based on the mass spectrometry. We further explore the strategies in implementing the concept of chemical exposome and discuss the available chemical exposome studies. Early progresses in the chemical exposome research are outlined, and major challenges are highlighted. In conclusion, efforts towards chemical exposome have only uncovered the tip of the iceberg, and further advancement in measurement techniques, computational tools, high-throughput data analysis, and standardization may allow more exciting discoveries concerning the role of exposome in human health and disease.}, number={3}, journal={TOXICS}, author={Xue, Jingchuan and Lai, Yunjia and Liu, Chih-Wei and Ru, Hongyu}, year={2019}, month={Sep} } @article{levine_walker_marcellin-little_goulet_ru_2018, title={Detection of skin temperature differences using palpation by manual physical therapists and lay individuals}, volume={26}, ISSN={["2042-6186"]}, DOI={10.1080/10669817.2018.1427908}, abstractNote={Abstract Objectives—To evaluate the accuracy of detection of temperature differences among skin sites of lay individuals and manual physical therapists.Methods— Forty-four manual physical therapists and 44 lay individuals were recruited. Subjects palpated two temperature-controlled surfaces that ranged in temperature between 30 and 35 °C and varied randomly by 1, 2, 3, 4, or 5 °C for 10 s. The subjects were then asked to identify the warmer pad.Results— Accuracy increased with larger temperature differences. Accuracy of detection of 1 and 3 °C temperature differences was higher in manual physical therapists than lay individuals.Discussion— Palpation can be used to accurately detecting temperature differences between sites and is more accurately performed by an experienced practitioner. Level of Evidence: 3b}, number={2}, journal={JOURNAL OF MANUAL & MANIPULATIVE THERAPY}, author={Levine, David and Walker, J. Randy and Marcellin-Little, Denis J. and Goulet, Ron and Ru, Hongyu}, year={2018}, pages={97–101} } @article{chi_bian_gao_tu_lai_ru_lu_2018, title={Effects of the Artificial Sweetener Neotame on the Gut Microbiome and Fecal Metabolites in Mice}, volume={23}, ISSN={["1420-3049"]}, DOI={10.3390/molecules23020367}, abstractNote={Although artificial sweeteners are widely used in food industry, their effects on human health remain a controversy. It is known that the gut microbiota plays a key role in human metabolism and recent studies indicated that some artificial sweeteners such as saccharin could perturb gut microbiome and further affect host health, such as inducing glucose intolerance. Neotame is a relatively new low-caloric and high-intensity artificial sweetener, approved by FDA in 2002. However, the specific effects of neotame on gut bacteria are still unknown. In this study, we combined high-throughput sequencing and gas chromatography–mass spectrometry (GC-MS) metabolomics to investigate the effects of neotame on the gut microbiome and fecal metabolite profiles of CD-1 mice. We found that a four-week neotame consumption reduced the alpha-diversity and altered the beta-diversity of the gut microbiome. Firmicutes was largely decreased while Bacteroidetes was significantly increased. The Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis also indicated that the control mice and neotame-treated mice have different metabolic patterns and some key genes such as butyrate synthetic genes were decreased. Moreover, neotame consumption also changed the fecal metabolite profiles. Dramatically, the concentrations of multiple fatty acids, lipids as well as cholesterol in the feces of neotame-treated mice were consistently higher than controls. Other metabolites, such as malic acid and glyceric acid, however, were largely decreased. In conclusion, our study first explored the specific effects of neotame on mouse gut microbiota and the results may improve our understanding of the interaction between gut microbiome and neotame and how this interaction could influence the normal metabolism of host bodies.}, number={2}, journal={MOLECULES}, author={Chi, Liang and Bian, Xiaoming and Gao, Bei and Tu, Pengcheng and Lai, Yunjia and Ru, Hongyu and Lu, Kun}, year={2018}, month={Feb} } @article{chi_xue_tu_lai_ru_lu_2019, title={Gut microbiome disruption altered the biotransformation and liver toxicity of arsenic in mice}, volume={93}, ISSN={["1432-0738"]}, DOI={10.1007/s00204-018-2332-7}, abstractNote={The mammalian gut microbiome (GM) plays a critical role in xenobiotic biotransformation and can profoundly affect the toxic effects of xenobiotics. Previous in vitro studies have demonstrated that gut bacteria have the capability to metabolize arsenic (As); however, the specific roles of the gut microbiota in As metabolism in vivo and the toxic effects of As are largely unknown. Here, we administered sodium arsenite to conventionally raised mice (with normal microbiomes) and GM-disrupted mice with antibiotics to investigate the role of the gut microbiota in As biotransformation and its toxicity. We found that the urinary total As levels of GM-disrupted mice were much higher, but the fecal total As levels were lower, than the levels in the conventionally raised mice. In vitro experiments, in which the GM was incubated with As, also demonstrated that the gut bacteria could adsorb or take up As and thus reduce the free As levels in the culture medium. With the disruption of the gut microbiota, arsenic biotransformation was significantly perturbed. Of note, the urinary monomethylarsonic acid/dimethylarsinic acid ratio, a biomarker of arsenic metabolism and toxicity, was markedly increased. Meanwhile, the expression of genes of one-carbon metabolism, including folr2, bhmt, and mthfr, was downregulated, and the liver S-adenosylmethionine (SAM) levels were significantly decreased in the As-treated GM-disrupted mice only. Moreover, As exposure altered the expression of genes of the p53 signaling pathway, and the expression of multiple genes associated with hepatocellular carcinoma (HCC) was also changed in the As-treated GM-disrupted mice only. Collectively, disruption of the GM enhances the effect of As on one-carbon metabolism, which could in turn affect As biotransformation. GM disruption also increases the toxic effects of As and may increase the risk of As-induced HCC in mice.}, number={1}, journal={ARCHIVES OF TOXICOLOGY}, author={Chi, Liang and Xue, Jingchuan and Tu, Pengcheng and Lai, Yunjia and Ru, Hongyu and Lu, Kun}, year={2019}, month={Jan}, pages={25–35} } @misc{chi_gao_tu_liu_xue_lai_ru_lu_2018, title={Individual susceptibility to arsenic-induced diseases: the role of host genetics, nutritional status, and the gut microbiome}, volume={29}, ISSN={["1432-1777"]}, DOI={10.1007/s00335-018-9736-9}, abstractNote={Arsenic (As) contamination in water or food is a global issue affecting hundreds of millions of people. Although As is classified as a group 1 carcinogen and is associated with multiple diseases, the individual susceptibility to As-related diseases is highly variable, such that a proportion of people exposed to As have higher risks of developing related disorders. Many factors have been found to be associated with As susceptibility. One of the main sources of the variability found in As susceptibility is the variation in the host genome, namely, polymorphisms of many genes involved in As transportation, biotransformation, oxidative stress response, and DNA repair affect the susceptibility of an individual to As toxicity and then influence the disease outcomes. In addition, lifestyles and many nutritional factors, such as folate, vitamin C, and fruit, have been found to be associated with individual susceptibility to As-related diseases. Recently, the interactions between As exposure and the gut microbiome have been of particular concern. As exposure has been shown to perturb gut microbiome composition, and the gut microbiota has been shown to also influence As metabolism, which raises the question of whether the highly diverse gut microbiota contributes to As susceptibility. Here, we review the literature and summarize the factors, such as host genetics and nutritional status, that influence As susceptibility, and we also present potential mechanisms of how the gut microbiome may influence As metabolism and its toxic effects on the host to induce variations in As susceptibility. Challenges and future directions are also discussed to emphasize the importance of characterizing the specific role of these factors in interindividual susceptibility to As-related diseases.}, number={1-2}, journal={MAMMALIAN GENOME}, author={Chi, Liang and Gao, Bei and Tu, Pengcheng and Liu, Chih-Wei and Xue, Jingchuan and Lai, Yunjia and Ru, Hongyu and Lu, Kun}, year={2018}, month={Feb}, pages={63–79} } @article{liu_chi_tu_xue_ru_lu_2019, title={Isobaric Labeling Quantitative Metaproteomics for the Study of Gut Microbiome Response to Arsenic}, volume={18}, ISSN={["1535-3907"]}, DOI={10.1021/acs.jproteome.8b00666}, abstractNote={Quantitative metaproteomics is a relatively new research field that applies proteomics techniques to study microbial proteins of the microbiome and holds great potential in truly quantifying the functional proteins actually expressed by microbes in the biological environment, such as the gastrointestinal tract. The significant association between arsenic exposure and gut microbiome perturbations has been reported; however, metaproteomics has not yet been applied to study arsenic-induced proteome changes of the microbiome. Most importantly, to our knowledge, isobaric-labeling-based large-scale metaproteomics has not been reported using the advanced database-search approaches such as MetaPro-IQ and matched metagenome database-search strategies to provide high quantification accuracy and fewer missing quantification values. In the present study, a new experimental workflow coupled to isobaric labeling and MetaPro-IQ was demonstrated for the metaproteomics study of arsenic-induced gut microbiome perturbations. The advantages of this workflow were also discussed. For all 18 fecal samples analyzed, 7611 protein groups were quantified without any missing values. The consistent results of expression profiles were observed between 16S rRNA gene sequencing and metaproteomics. This isobaric-labeling-based workflow demonstrated the significant improvement of quantitative metaproteomics for gut microbiome study.}, number={3}, journal={JOURNAL OF PROTEOME RESEARCH}, author={Liu, Chih-Wei and Chi, Liang and Tu, Pengcheng and Xue, Jingchuan and Ru, Hongyu and Lu, Kun}, year={2019}, month={Mar}, pages={970–981} } @article{bian_chi_gao_tu_ru_lu_2017, title={Gut Microbiome Response to Sucralose and Its Potential Role in Inducing Liver Inflammation in Mice}, volume={8}, ISSN={["1664-042X"]}, DOI={10.3389/fphys.2017.00487}, abstractNote={Sucralose is the most widely used artificial sweetener, and its health effects have been highly debated over the years. In particular, previous studies have shown that sucralose consumption can alter the gut microbiota. The gut microbiome plays a key role in processes related to host health, such as food digestion and fermentation, immune cell development, and enteric nervous system regulation. Inflammation is one of the most common effects associated with gut microbiome dysbiosis, which has been linked to a series of human diseases, such as diabetes and obesity. The aim of this study was to investigate the structural and functional effects of sucralose on the gut microbiota and associated inflammation in the host. In this study, C57BL/6 male mice received sucralose in their drinking water for 6 months. The difference in gut microbiota composition and metabolites between control and sucralose-treated mice was determined using 16S rRNA gene sequencing, functional gene enrichment analysis and metabolomics. Inflammatory gene expression in tissues was analyzed by RT-PCR. Alterations in bacterial genera showed that sucralose affects the gut microbiota and its developmental dynamics. Enrichment of bacterial pro-inflammatory genes and disruption in fecal metabolites suggest that 6-month sucralose consumption at the human acceptable daily intake (ADI) may increase the risk of developing tissue inflammation by disrupting the gut microbiota, which is supported by elevated pro-inflammatory gene expression in the liver of sucralose-treated mice. Our results highlight the role of sucralose-gut microbiome interaction in regulating host health-related processes, particularly chronic inflammation.}, journal={FRONTIERS IN PHYSIOLOGY}, author={Bian, Xiaoming and Chi, Liang and Gao, Bei and Tu, Pengcheng and Ru, Hongyu and Lu, Kun}, year={2017}, month={Jul} } @article{chi_gao_bian_tu_ru_lu_2017, title={Manganese-induced sex-specific gut microbiome perturbations in C57BL/6 mice}, volume={331}, ISSN={["1096-0333"]}, DOI={10.1016/j.taap.2017.06.008}, abstractNote={Overexposure to manganese (Mn) leads to toxic effects, such as promoting the development of Parkinson's-like neurological disorders. The gut microbiome is deeply involved in immune development, host metabolism, and xenobiotics biotransformation, and significantly influences central nervous system (CNS) via the gut-brain axis, i.e. the biochemical signaling between the gastrointestinal tract and the CNS. However, it remains unclear whether Mn can affect the gut microbiome and its metabolic functions, particularly those linked to neurotoxicity. In addition, sex-specific effects of Mn have been reported, with no mechanism being identified yet. Recently, we have shown that the gut microbiome is largely different between males and females, raising the possibility that differential gut microbiome responses may contribute to sex-selective toxicity of Mn. Here, we applied high-throughput sequencing and gas chromatography-mass spectrometry (GC-MS) metabolomics to explore how Mn 2+ exposure affects the gut microbiome and its metabolism in C57BL/6 mice. Mn 2+ exposure perturbed the gut bacterial compositions, functional genes and fecal metabolomes in a highly sex-specific manner. In particular, bacterial genes and/or key metabolites of neurotransmitter synthesis and pro-inflammatory mediators are significantly altered by Mn 2+ exposure, which can potentially affect chemical signaling of gut-brain interactions. Likewise, functional genes involved in iron homeostasis, flagellar motility, quorum sensing, and Mn transportation/oxidation are also widely changed by Mn 2+ exposure. Taken together, this study has demonstrated that Mn 2+ exposure perturbs the gut microbiome and its metabolic functions, which highlights the potential role of the gut microbiome in Mn 2+ toxicity, particularly its sex-specific toxic effects.}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={Chi, Liang and Gao, Bei and Bian, Xiaoming and Tu, Pengcheng and Ru, Hongyu and Lu, Kun}, year={2017}, month={Sep}, pages={142–153} } @article{gao_chi_mahbub_bian_tu_ru_lu_2017, title={Multi-Omits Reveals that Lead Exposure Disturbs Gut Microbiome Development, Key Metabolites, and Metabolic Pathways}, volume={30}, ISSN={["1520-5010"]}, DOI={10.1021/acs.chemrestox.6b00401}, abstractNote={Lead exposure remains a global public health issue, and the recent Flint water crisis has renewed public concern about lead toxicity. The toxicity of lead has been well established in a variety of systems and organs. The gut microbiome has been shown to be highly involved in many critical physiological processes, including food digestion, immune system development, and metabolic homeostasis. However, despite the key role of the gut microbiome in human health, the functional impact of lead exposure on the gut microbiome has not been studied. The aim of this study is to define gut microbiome toxicity induced by lead exposure in C57BL/6 mice using multiomics approaches, including 16S rRNA sequencing, whole genome metagenomics sequencing, and gas chromatography-mass spectrometry (GC-MS) metabolomics. 16S rRNA sequencing revealed that lead exposure altered the gut microbiome trajectory and phylogenetic diversity. Metagenomics sequencing and metabolomics profiling showed that numerous metabolic pathways, including vitamin E, bile acids, nitrogen metabolism, energy metabolism, oxidative stress, and the defense/detoxification mechanism, were significantly disturbed by lead exposure. These perturbed molecules and pathways may have important implications for lead toxicity in the host. Taken together, these results demonstrated that lead exposure not only altered the gut microbiome community structures/diversity but also greatly affected metabolic functions, leading to gut microbiome toxicity.}, number={4}, journal={CHEMICAL RESEARCH IN TOXICOLOGY}, author={Gao, Bei and Chi, Liang and Mahbub, Ridwan and Bian, Xiaoming and Tu, Pengcheng and Ru, Hongyu and Lu, Kun}, year={2017}, month={Apr}, pages={996–1005} } @article{gao_bian_chi_tu_ru_lu_2017, title={Organophosphate Diazinon Altered Quorum Sensing, Cell Motility, Stress Response, and Carbohydrate Metabolism of Gut Microbiome}, volume={157}, ISSN={["1096-0929"]}, DOI={10.1093/toxsci/kfx053}, abstractNote={The gut microbiome plays a key role in energy production, immune system development, and host resistance against invading pathogens, etc. Disruption of gut bacterial homeostasis is associated with a number of human diseases. Several environmental chemicals have been reported to induce alterations of the gut microbiome. Diazinon, one of important organophosphate insecticides, has been widely used in agriculture. Diazinon and its metabolites are readily detected in different environmental settings and human urine. The toxicity of organophosphates has been a long-standing public health concern. We recently demonstrated that organophosphate insecticide diazinon perturbed the gut microbiome composition of mice. However, the functional impact of exposure on the gut microbiome has not been adequately assessed yet. In particular, the molecular mechanism responsible for exposure-induced microbial profile and community structure changes has not been identified. Therefore, in this study, we used metatranscriptomics to examine the effects of diazinon exposure on the gut metatranscriptome in C57BL/6 mice. Herein, we demonstrated for the first time that organophosphate diazinon modulated quorum sensing, which may serve as a key mechanism to regulate bacterial population, composition, and more importantly, their functional genes. In addition, we also found that diazinon exposure activated diverse stress response pathways and profoundly impaired energy metabolism of gut bacteria. These findings provide new understandings of the functional interplay between the gut microbiome and environmental chemicals, such as organophosphates.}, number={2}, journal={TOXICOLOGICAL SCIENCES}, author={Gao, Bei and Bian, Xiaoming and Chi, Liang and Tu, Pengcheng and Ru, Hongyu and Lu, Kun}, year={2017}, month={Jun}, pages={354–364} } @article{gao_tu_bian_chi_ru_lu_2017, title={Profound perturbation induced by triclosan exposure in mouse gut microbiome: a less resilient microbial community with elevated antibiotic and metal resistomes}, volume={18}, ISSN={["2050-6511"]}, DOI={10.1186/s40360-017-0150-9}, abstractNote={Environmental chemical-induced perturbations of gut microbiome are associated with a series of adverse health outcomes. The effects of triclosan on human health have been controversial in recent years. The purpose of this study is to investigate the functional impact of triclosan on the mouse gut microbiome and the link between triclosan exposure and resistomes in gut bacteria.We combined 16S rRNA gene sequencing and shotgun metagenomics sequencing to examine the compositional and functional impact of triclosan exposure on the gut microbiota of C57BL/6 mice.16S rRNA sequencing results revealed that 13-week triclosan exposure in drinking water induced significant perturbations in mouse gut bacterial assemblages with distinct trajectories compared to controls. Metagenomics sequencing results indicated a remarkable enrichment of gut bacterial genes related to triclosan resistance, stress response, antibiotic resistance and heavy metal resistance.Triclosan exposure has a profound impact on the mouse gut microbiome by inducing perturbations at both compositional and functional levels. To our best knowledge, this is the first evidence regarding the functional alterations of gut microbiome induced by triclosan exposure, which may provide novel mechanistic insights into triclosan exposure and associated diseases.}, journal={BMC PHARMACOLOGY & TOXICOLOGY}, author={Gao, Bei and Tu, Pengcheng and Bian, Xiaoming and Chi, Liang and Ru, Hongyu and Lu, Kun}, year={2017}, month={Jun} } @article{bian_tu_chi_gao_ru_lu_2017, title={Saccharin induced liver inflammation in mice by altering the gut microbiota and its metabolic functions}, volume={107}, ISSN={["1873-6351"]}, DOI={10.1016/j.fct.2017.04.045}, abstractNote={Maintaining the balance of the gut microbiota and its metabolic functions is vital for human health, however, this balance can be disrupted by various external factors including food additives. A range of food and beverages are sweetened by saccharin, which is generally considered to be safe despite controversial debates. However, recent studies indicated that saccharin perturbed the gut microbiota. Inflammation is frequently associated with disruptions of the gut microbiota. The aim of this study is to investigate the relationship between host inflammation and perturbed gut microbiome by saccharin. C57BL/6J male mice were treated with saccharin in drinking water for six months. Q-PCR was used to detect inflammatory markers in mouse liver, while 16S rRNA gene sequencing and metabolomics were used to reveal changes of the gut microbiota and its metabolomic profiles. Elevated expression of pro-inflammatory iNOS and TNF-α in liver indicated that saccharin induced inflammation in mice. The altered gut bacterial genera, enriched orthologs of pathogen-associated molecular patterns, such as LPS and bacterial toxins, in concert with increased pro-inflammatory metabolites suggested that the saccharin-induced liver inflammation could be associated with the perturbation of the gut microbiota and its metabolic functions.}, journal={FOOD AND CHEMICAL TOXICOLOGY}, author={Bian, Xiaoming and Tu, Pengcheng and Chi, Liang and Gao, Bei and Ru, Hongyu and Lu, Kun}, year={2017}, month={Sep}, pages={530–539} } @article{chi_bian_gao_tu_ru_lu_2017, title={The Effects of an Environmentally Relevant Level of Arsenic on the Gut Microbiome and Its Functional Metagenome}, volume={160}, ISSN={["1096-0929"]}, DOI={10.1093/toxsci/kfx174}, abstractNote={Multiple environmental factors induce dysbiosis in the gut microbiome and cause a variety of human diseases. Previously, we have first demonstrated that arsenic alters the composition of the gut microbiome. However, the functional impact of arsenic on the gut microbiome has not been adequately assessed, particularly at environmentally relevant concentrations. In this study, we used 16S rRNA sequencing and metagenomics sequencing to investigate how exposure to 100 ppb arsenic for 13 weeks alters the composition and functional capacity of the gut microbiome in mice. Arsenic exposure altered the alpha and beta diversities as well as the composition profile of the gut microbiota. Metagenomics data revealed that the abundances of genes involved in carbohydrate metabolism, especially pyruvate fermentation, short-chain fatty acid synthesis, and starch utilization, and were significantly changed. Moreover, lipopolysaccharide biosynthesis genes, multiple stress response genes, and DNA repair genes were significantly increased in the gut microbiome of arsenic-exposed mice. The genes involved in the production or processing of multiple vitamins, including folic acid and vitamins B6, B12, and K2, were also enriched in arsenic-treated mice. In, addition, genes involved in multidrug resistance and conjugative transposon proteins were highly increased after treatment with arsenic. In conclusion, we demonstrate that arsenic exposure, at an environmentally relevant dose, not only perturbed the communal composition of the gut microbiome but also profoundly altered a variety of important bacterial functional pathways.}, number={2}, journal={TOXICOLOGICAL SCIENCES}, author={Chi, Liang and Bian, Xiaoming and Gao, Bei and Tu, Pengcheng and Ru, Hongyu and Lu, Kun}, year={2017}, month={Dec}, pages={193–204} } @article{bian_chi_gao_tu_ru_lu_2017, title={The artificial sweetener acesulfame potassium affects the gut microbiome and body weight gain in CD-1 mice}, volume={12}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0178426}, abstractNote={Artificial sweeteners have been widely used in the modern diet, and their observed effects on human health have been inconsistent, with both beneficial and adverse outcomes reported. Obesity and type 2 diabetes have dramatically increased in the U.S. and other countries over the last two decades. Numerous studies have indicated an important role of the gut microbiome in body weight control and glucose metabolism and regulation. Interestingly, the artificial sweetener saccharin could alter gut microbiota and induce glucose intolerance, raising questions about the contribution of artificial sweeteners to the global epidemic of obesity and diabetes. Acesulfame-potassium (Ace-K), a FDA-approved artificial sweetener, is commonly used, but its toxicity data reported to date are considered inadequate. In particular, the functional impact of Ace-K on the gut microbiome is largely unknown. In this study, we explored the effects of Ace-K on the gut microbiome and the changes in fecal metabolic profiles using 16S rRNA sequencing and gas chromatography-mass spectrometry (GC-MS) metabolomics. We found that Ace-K consumption perturbed the gut microbiome of CD-1 mice after a 4-week treatment. The observed body weight gain, shifts in the gut bacterial community composition, enrichment of functional bacterial genes related to energy metabolism, and fecal metabolomic changes were highly gender-specific, with differential effects observed for males and females. In particular, ace-K increased body weight gain of male but not female mice. Collectively, our results may provide a novel understanding of the interaction between artificial sweeteners and the gut microbiome, as well as the potential role of this interaction in the development of obesity and the associated chronic inflammation.}, number={6}, journal={PLOS ONE}, author={Bian, Xiaoming and Chi, Liang and Gao, Bei and Tu, Pengcheng and Ru, Hongyu and Lu, Kun}, year={2017}, month={Jun} } @article{gao_chi_tu_bian_thomas_ru_lu_2018, title={The organophosphate malathion disturbs gut microbiome development and the quorum-Sensing system}, volume={283}, ISSN={["1879-3169"]}, DOI={10.1016/j.toxlet.2017.10.023}, abstractNote={The gut microbiome has tremendous potential to impact health and disease. Various environmental toxicants, including insecticides, have been shown to alter gut microbiome community structures. However, the mechanism that compositionally and functionally regulates gut microbiota remains unclear. Quorum sensing is known to modulate intra- and interspecies gene expression and coordinate population responses. It is unknown whether quorum sensing is disrupted when environmental toxicants cause perturbations in the gut microbiome community structure. To reveal the response of the quorum-sensing system to environmental exposure, we use a combination of Illumina-based 16S rRNA gene amplicon and shotgun metagenome sequencing to examine the impacts of a widely used organophosphate insecticide, malathion, on the gut microbiome trajectory, quorum sensing system and behaviors related to quorum sensing, such as motility and pathogenicity. Our results demonstrated that malathion perturbed the gut microbiome development, quorum sensing and quorum sensing related behaviors. These findings may provide a novel mechanistic understanding of the role of quorum-sensing in the gut microbiome toxicity of malathion.}, journal={TOXICOLOGY LETTERS}, author={Gao, Bei and Chi, Liang and Tu, Pengcheng and Bian, Xiaoming and Thomas, Jesse and Ru, Hongyu and Lu, Kun}, year={2018}, month={Feb}, pages={52–57} }