Publications by authors named "Leluo Guan"

26 Publications

  • Page 1 of 1

The potential for mitigation of methane emissions in ruminants through the application of metagenomics, metabolomics, and other -OMICS technologies.

J Anim Sci 2021 Oct;99(10)

Centre for Genetic Improvement of Livestock (CGIL), Department of Animal Biosciences, University of Guelph, Guelph, Ontario, N1G 2W1, Canada.

Ruminant supply chains contribute 5.7 gigatons of CO2-eq per annum, which represents approximately 80% of the livestock sector emissions. One of the largest sources of emission in the ruminant sector is methane (CH4), accounting for approximately 40% of the sectors total emissions. With climate change being a growing concern, emphasis is being put on reducing greenhouse gas emissions, including those from ruminant production. Various genetic and environmental factors influence cattle CH4 production, such as breed, genetic makeup, diet, management practices, and physiological status of the host. The influence of genetic variability on CH4 yield in ruminants indicates that genomic selection for reduced CH4 emissions is possible. Although the microbiology of CH4 production has been studied, further research is needed to identify key differences in the host and microbiome genomes and how they interact with one another. The advancement of "-omics" technologies, such as metabolomics and metagenomics, may provide valuable information in this regard. Improved understanding of genetic mechanisms associated with CH4 production and the interaction between the microbiome profile and host genetics will increase the rate of genetic progress for reduced CH4 emissions. Through a systems biology approach, various "-omics" technologies can be combined to unravel genomic regions and genetic markers associated with CH4 production, which can then be used in selective breeding programs. This comprehensive review discusses current challenges in applying genomic selection for reduced CH4 emissions, and the potential for "-omics" technologies, especially metabolomics and metagenomics, to minimize such challenges. The integration and evaluation of different levels of biological information using a systems biology approach is also discussed, which can assist in understanding the underlying genetic mechanisms and biology of CH4 production traits in ruminants and aid in reducing agriculture's overall environmental footprint.
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http://dx.doi.org/10.1093/jas/skab193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480417PMC
October 2021

TL Downregulates the Ileal Expression of Genes Involved in Immune Responses in Broiler Chickens to Improve Growth Performance.

Microorganisms 2021 Feb 13;9(2). Epub 2021 Feb 13.

College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.

TL promotes broiler chicken performance by improving nutrient absorption and utilization and reducing intestinal inflammation. In this study, RNA-sequencing (RNA-seq)-based transcriptomes of ileal tissues collected from probiotic-fed and control broiler chickens were analyzed to elucidate the effects of the probiotic TL, as a feed additive, on the gut immune function. In total, 475 genes were significantly differentially expressed between the ileum of probiotic-fed and control birds. The expression of genes encoding pyruvate kinase, prothymosin-α, and heat stress proteins was high in the ileum of probiotic-fed birds (FPKM > 500), but not in the control group. The gene ontology functional enrichment and pathway enrichment analyses revealed that the uniquely expressed genes in the control group were mostly involved in immune responses, whereas those in the probiotic group were involved in fibroblast growth factor receptor signaling pathways and positive regulation of cell proliferation. TL downregulated the expression of certain proinflammatory factors and affected the cytokine-cytokine receptor interaction pathway. Furthermore, TL in broiler diets altered the expression of genes involved in immune functions in the ileum. Thus, it might contribute to improved broiler growth by regulating the immune system and reducing intestinal damage in broilers.
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http://dx.doi.org/10.3390/microorganisms9020382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918048PMC
February 2021

Comparative Microbiome Analysis Reveals the Ecological Relationships Between Rumen Methanogens, Acetogens, and Their Hosts.

Front Microbiol 2020 30;11:1311. Epub 2020 Jun 30.

Department of Special Economic Animal Nutrition and Feed Science, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun, China.

Ruminant methane, which is generated by methanogens through the consumption of hydrogen and supports the normal function of the rumen ecosystem, is a major source of greenhouse gases. Reductive acetogenesis by acetogens is a possible alternative sink that can dispose of hydrogen for acetate production. However, the distribution of rumen methanogens and acetogens along with the relationships among methanogens, acetogens, and their host are poorly understood. Therefore, we investigated the rumen methanogen and acetogen communities of 97 individual animals representing 14 ruminant species within three ruminant families Cervidae (deer), Bovidae (bovid), and Moschidae (musk deer). The results showed that the spp. and acetogens associated with Eubacteriaceae were the most widespread methanogens and acetogens, respectively. However, other methanogens and acetogens exhibited host specificity in the rumen of reindeer and Chinese muntjac deer. Acetogen and methanogen communities were not correlated in these species, and the phylosymbiosis signature between host phylogeny and the composition of both communities was lacking. The abundance of was negatively correlated with the degree of papillation of the rumen wall. Finally, co-occurrence analysis showed that the variation of the predicted methane yields was characterized by the interactive patterns between methanogens, acetogens, and concentrations of rumen metabolites. Our results show that rumen methanogen and acetogen communities have low compositional interdependence and do not exhibit parallel host evolution, which suggests that the strategies for mitigating methane production should be based on a species-specific rumen microbiota analysis.
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http://dx.doi.org/10.3389/fmicb.2020.01311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344211PMC
June 2020

Transcriptional changes in the hypothalamus, pituitary, and mammary gland underlying decreased lactation performance in mice under heat stress.

FASEB J 2019 11 31;33(11):12588-12601. Epub 2019 Aug 31.

College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang, China; and.

Because of climate change, heat stress (HS) causes more and more impacts on dairy animals to decrease lactation performance. The neuroendocrine system is key in regulating systemic physiological processes and milk synthesis. However, the hypothalamic-pituitary axis response to HS is still unclear. In this study, a group of lactating mice underwent a daily 2-h heat treatment (36°C) for 14 d to explore possible cross-talk between the hypothalamic-pituitary axis and mammary gland under HS. Transcriptome analyses by multitissue RNA-Seq indicated the possible mechanisms of reduced lactation performance in animals under HS. In the hypothalamus, the cAMP signaling pathway was activated to resist neuronal death, and the expression of downstream genes was increased to promote cell survival under HS. Reduced food intake might be caused by down-regulated appetite-related peptide, whereas up-regulated neuropeptide Y acted to attenuate reduced food intake. In pituitary, energy stress from lower food intake might result in reduced secretion of prolactin and growth hormone. Under HS, the mammary gland may undergo hypoxic stress, causing mammary epithelial cell apoptosis. Together, these data showed systemic changes in tissues to accommodate the effects of HS on lactation.-Han, J., Shao, J., Chen, Q., Sun, H., Guan, L., Li, Y., Liu, J., Liu, H. Transcriptional changes in the hypothalamus, pituitary, and mammary gland underlying decreased lactation performance in mice under heat stress.
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http://dx.doi.org/10.1096/fj.201901045RDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902726PMC
November 2019

Days-in-Milk and Parity Affected Serum Biochemical Parameters and Hormone Profiles in Mid-Lactation Holstein Cows.

Animals (Basel) 2019 May 10;9(5). Epub 2019 May 10.

Institute of Dairy Science, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.

It is well known that serum biochemical parameters and hormones contribute greatly to the physiological and metabolic status of dairy cows. However, few studies have focused on the variation of these serum parameters in multiparous mid-lactation cows without the interference of diet and management. A total of 287 Holstein dairy cows fed the same diet and maintained under the same management regime were selected from a commercial dairy farm to evaluate the effects of days-in-milk (DIM) and parity on serum biochemical parameters and hormone profiles. Milk yield and milk protein content were affected by DIM and parity ( < 0.05). Milk protein yield showed a numerically decreasing trend with parity, and it was relatively constant in cows with parities between 2 and 4 but lower in cows with parity 6 ( = 0.020). Ten and five serum biochemical parameters related to protein status, energy metabolism, liver and kidney function, and oxidative stress were affected by DIM and parity, respectively ( < 0.05). Glucagon, insulin-like growth factor 1 concentration, and the revised quantitative insulin sensitivity check index were significantly different ( < 0.05) among cows with different DIM. Parity had no effect on hormone concentrations. An interaction between DIM and parity effect was only detected for glucagon concentration ( = 0.015), which showed a significantly increasing trend with DIM and overall decreasing trend with parity. In summary, DIM and parity played an important role in affecting the serum biochemical parameters and/or hormones of dairy cows, with serum parameters affected more by DIM than parity.
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http://dx.doi.org/10.3390/ani9050230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562902PMC
May 2019

Addressing Global Ruminant Agricultural Challenges Through Understanding the Rumen Microbiome: Past, Present, and Future.

Front Microbiol 2018 25;9:2161. Epub 2018 Sep 25.

Department of Microbiology, Universidade Federal de Viçosa, Viçosa, Brazil.

The rumen is a complex ecosystem composed of anaerobic bacteria, protozoa, fungi, methanogenic archaea and phages. These microbes interact closely to breakdown plant material that cannot be digested by humans, whilst providing metabolic energy to the host and, in the case of archaea, producing methane. Consequently, ruminants produce meat and milk, which are rich in high-quality protein, vitamins and minerals, and therefore contribute to food security. As the world population is predicted to reach approximately 9.7 billion by 2050, an increase in ruminant production to satisfy global protein demand is necessary, despite limited land availability, and whilst ensuring environmental impact is minimized. Although challenging, these goals can be met, but depend on our understanding of the rumen microbiome. Attempts to manipulate the rumen microbiome to benefit global agricultural challenges have been ongoing for decades with limited success, mostly due to the lack of a detailed understanding of this microbiome and our limited ability to culture most of these microbes outside the rumen. The potential to manipulate the rumen microbiome and meet global livestock challenges through animal breeding and introduction of dietary interventions during early life have recently emerged as promising new technologies. Our inability to phenotype ruminants in a high-throughput manner has also hampered progress, although the recent increase in "omic" data may allow further development of mathematical models and rumen microbial gene biomarkers as proxies. Advances in computational tools, high-throughput sequencing technologies and cultivation-independent "omics" approaches continue to revolutionize our understanding of the rumen microbiome. This will ultimately provide the knowledge framework needed to solve current and future ruminant livestock challenges.
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http://dx.doi.org/10.3389/fmicb.2018.02161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167468PMC
September 2018

The Development of Microbiota and Metabolome in Small Intestine of Sika Deer () from Birth to Weaning.

Front Microbiol 2018 23;9. Epub 2018 Jan 23.

Jilin Provincial Key Laboratory for Molecular Biology of Special Economic Animals, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun, China.

The dense and diverse community of microorganisms inhabiting the gastrointestinal tract of ruminant animals plays critical roles in the metabolism and absorption of nutrients, and gut associated immune function. Understanding microbial colonization in the small intestine of new born ruminants is a vital first step toward manipulating gut function through interventions during early life to produce long-term positive effects on host productivity and health. Yet the knowledge of microbiota colonization and its induced metabolites of small intestine during early life is still limited. In the present study, we examined the microbiota and metabolome in the jejunum and ileum of neonatal sika deer () from birth to weaning at days 1, 42, and 70. The microbial data showed that diversity and richness were increased with age, but a highly individual variation was observed at day 1. Principal coordinate analysis revealed significant differences in microbial community composition across three time points in the jejunum and ileum. The abundance of spp., spp., -, and spp. tended to be decreased, while the proportion of spp., spp., spp., 1 and spp. was significantly increased with age. For metabolome, metabolites separated from each other across the three time points in both jejunum and ileum. Moreover, the amounts of methionine, threonine, and putrescine were increased, while the amounts of myristic acid and pentadecanoic acid were decreased with age, respectively. The present study demonstrated that microbiota colonization and the metabolome becomes more developed in the small intestine with age. This may shed new light on the microbiota-metabolome-immune interaction during development.
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http://dx.doi.org/10.3389/fmicb.2018.00004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5787063PMC
January 2018

Effect of changing forage on the dynamic variation in rumen fermentation in sheep.

Anim Sci J 2018 Jan 25;89(1):122-131. Epub 2017 Sep 25.

Institute of Dairy Science, College of Animal Sciences, Zhejiang University, Hangzhou, China.

To better understand rumen adaptation during dietary transitions between high- and low-quality forages, 10 rumen-cannulated Hu sheep were randomly allocated to two dietary treatments (five sheep each) with the same concentrate-to-forage ratio and concentration mixture, but different forage sequences: (i) alfalfa hay (AH) to corn stover (CS) and back to AH; and (ii) CS to AH and back to CS. A significant decrease in the rumen microbial protein concentration was observed on day 6 after dietary transition whether the transition was from AH to CS or from CS to AH, and this was accompanied by an increase in the ammonia nitrogen concentration as well as a decrease in the total volatile fatty acids concentration and pH. However, after transitioning back to the original forage, the rumen fermentation parameters returned to their initial levels within 2 weeks. Our findings suggest that abrupt substitutions of forages with large nutrient differences could influence rumen function to some extent, but recovery can occur within 2 weeks without detrimental effects. Furthermore, we speculate that the variation of fermentation in the first 6 days may indicate an important rumen transition stage that requires further study.
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http://dx.doi.org/10.1111/asj.12915DOI Listing
January 2018

Fish oil mitigates myosteatosis and improves chemotherapy efficacy in a preclinical model of colon cancer.

PLoS One 2017 23;12(8):e0183576. Epub 2017 Aug 23.

Alberta Institute for Human Nutrition, Department of Agricultural, Food and Nutritional Sciences, University of Alberta, Edmonton, AB, Canada.

Background: This study aimed to assess whether feeding a diet containing fish oil was efficacious in reducing tumor- and subsequent chemotherapy-associated myosteatosis, and improving tumor response to treatment.

Methods: Female Fischer 344 rats were fed either a control diet for the entire study (control), or switched to a diet containing fish oil (2.0 g /100 g of diet) one week prior to tumor implantation (long term fish oil) or at the start of chemotherapy (adjuvant fish oil). Chemotherapy (irinotecan plus 5-fluorouracil) was initiated 2 weeks after tumor implantation (cycle-1) and 1 week thereafter (cycle-2). Reference animals received no tumor or treatment and only consumed the control diet. All skeletal muscle measures were conducted in the gastrocnemius. To assess myosteatosis, lipids were assessed histologically by Oil Red O staining and total triglyceride content was quantified by gas chromatography. Expression of adipogenic transcription factors were assessed at the mRNA level by real-time RT-PCR.

Results: Feeding a diet containing fish oil significantly reduced tumor- and subsequent chemotherapy-associated increases in skeletal muscle neutral lipid (p<0.001) and total triglyceride content (p<0.03), and expression of adipogenic transcription factors (p<0.01) compared with control diet fed animals. The adjuvant fish oil diet was as effective as the long term fish oil diet in mitigating chemotherapy-associated skeletal muscle fat content, and in reducing tumor volume during chemotherapy compared with control fed animals (p<0.01).

Conclusion: Long term and adjuvant fish oil diets are equally efficacious in reducing chemotherapy-associated myosteatosis that may be occurring by reducing expression of transcription factors involved in adipogenesis/lipogenesis, and improving tumor-response to chemotherapy in a neoplastic model.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0183576PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568380PMC
October 2017

Effects of dietary physical or nutritional factors on morphology of rumen papillae and transcriptome changes in lactating dairy cows based on three different forage-based diets.

BMC Genomics 2017 05 6;18(1):353. Epub 2017 May 6.

Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, T6G 2P5, Canada.

Background: Rumen epithelial tissue plays an important role in nutrient absorption and rumen health. However, whether forage quality and particle size impact the rumen epithelial morphology is unclear. The current study was conducted to elucidate the effects of forage quality and forage particle size on rumen epithelial morphology and to identify potential underlying molecular mechanisms by analyzing the transcriptome of the rumen epithelium (RE). To achieve these objectives, 18 mid-lactation dairy cows were allocated to three groups (6 cows per group), and were fed with one of three different forage-based diets, alfalfa hay (AH), corn stover (CS), and rice straw (RS) for 14 weeks, respectively. Ruminal volatile fatty acids (VFAs) and epithelial thickness were determined, and RNA-sequencing was conducted to identify the transcriptomic changes of rumen epithelial under different forage-based diets.

Results: The RS diet exhibited greater particle size but low quality, the AH diet was high nutritional value but small particle size, and CS diet was low quality and small particle size. The ruminal total VFA concentration was greater in AH compared with those in CS or RS. The width of the rumen papillae was greater in RS-fed cows than in cows fed AH or CS. In total, 31, 40, and 28 differentially expressed (DE, fold change > 2, FDR < 0.05) genes were identified via pair-wise comparisons including AH vs. CS, AH vs. RS, and RS vs. CS, respectively. Functional classification analysis of DE genes revealed dynamic changes in ion binding (such as DSG1) between AH and CS, proliferation and apoptotic processes (such as BAG3, HLA-DQA1, and UGT2B17) and complement activation (such as C7) between AH or RS and CS. The expression of HLA-DQA1 was down-regulated in RS compared with AH and CS, and the expression of UGT2B17 was down-regulated in RS compared with CS, with positive (R = 0.94) and negative (R = -0.96) correlation with the width of rumen epithelial papillae (P < 0.05), respectively.

Conclusion: Our results suggest that both nutrients (VFAs) and particle sizes can alter expression of genes involved in cell proliferation/apoptosis process and complement complex. Our results suggest that particle size may be more important in regulating rumen epithelial morphology when animals are fed with low-quality forage diets and the identified DE genes may affect the RE nutrient absorption or morphology of RE. Our findings provide insights into the effects of the dietary particle size in the future management of dairy cow feeding, that when cows were fed with low-quality forage (such as rice straw), smaller particle size may be beneficial for nutrients absorption and milk production.
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http://dx.doi.org/10.1186/s12864-017-3726-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5420399PMC
May 2017

Influence of Oleic Acid on Rumen Fermentation and Fatty Acid Formation In Vitro.

PLoS One 2016 14;11(6):e0156835. Epub 2016 Jun 14.

Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha, Hunan 410125, P.R. China.

A series of batch cultures were conducted to investigate the effects of oleic acid (OA) on in vitro ruminal dry matter degradability (IVDMD), gas production, methane (CH4) and hydrogen (H2) production, and proportion of fatty acids. Rumen fluid was collected from fistulated goats, diluted with incubation buffer, and then incubated with 500 mg Leymus chinensis meal supplemented with different amounts of OA (0, 20, 40, and 60 mg for the CON, OA20, OA40 and OA60 groups, respectively). Incubation was carried out anaerobically at 39°C for 48 h, and the samples were taken at 12, 24 and 48 h and subjected to laboratory analysis. Supplementation of OA decreased IVDMD, the cumulative gas production, theoretical maximum of gas production and CH4 production, but increased H2 production. However, no effect was observed on any parameters of rumen fermentation (pH, ammonia, production of acetate, propionate and butyrate and total volatile fatty acid production). The concentrations of some beneficial fatty acids, such as cis monounsaturated fatty acids and conjugated linoleic acid (CLA) were higher (P < 0.05) from OA groups than those from the control group at 12 h incubation. In summary, these results suggest that the OA supplementation in diet can reduce methane production and increase the amount of some beneficial fatty acids in vitro.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0156835PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907511PMC
July 2017

Bioinformatic analyses in early host response to Porcine Reproductive and Respiratory Syndrome virus (PRRSV) reveals pathway differences between pigs with alternate genotypes for a major host response QTL.

BMC Genomics 2016 Mar 8;17:196. Epub 2016 Mar 8.

Department of Animal Science, Iowa State University, 2255 Kildee Hall, Ames, IA, 50011, USA.

Background: A region on Sus scrofa chromosome 4 (SSC4) surrounding single nucleotide polymorphism (SNP) marker WUR10000125 (WUR) has been reported to be strongly associated with both weight gain and serum viremia in pigs after infection with PRRS virus (PRRSV). A proposed causal mutation in the guanylate binding protein 5 gene (GBP5) is predicted to truncate the encoded protein. To investigate transcriptional differences between WUR genotypes in early host response to PRRSV infection, an RNA-seq experiment was performed on globin depleted whole blood RNA collected on 0, 4, 7, 10 and 14 days post-infection (dpi) from eight littermate pairs with one AB (favorable) and one AA (unfavorable) WUR genotype animal per litter.

Results: Gene Ontology (GO) enrichment analysis of transcripts that were differentially expressed (DE) between dpi across both genotypes revealed an inflammatory response for all dpi when compared to day 0. However, at the early time points of 4 and 7dpi, several GO terms had higher enrichment scores compared to later dpi, including inflammatory response (p < 10(-7)), specifically regulation of NFkappaB (p < 0.01), cytokine, and chemokine activity (p < 0.01). At 10 and 14dpi, GO term enrichment indicated a switch to DNA damage response, cell cycle checkpoints, and DNA replication. Few transcripts were DE between WUR genotypes on individual dpi or averaged over all dpi, and little enrichment of any GO term was found. However, there were differences in expression patterns over time between AA and AB animals, which was confirmed by genotype-specific expression patterns of several modules that were identified in weighted gene co-expression network analyses (WGCNA). Minor differences between AA and AB animals were observed in immune response and DNA damage response (p = 0.64 and p = 0.11, respectively), but a significant effect between genotypes pointed to a difference in ion transport/homeostasis and the participation of G-coupled protein receptors (p = 8e-4), which was reinforced by results from regulatory and phenotypic impact factor analyses between genotypes.

Conclusion: We propose these pathway differences between WUR genotypes are the result of the inability of the truncated GBP5 of the AA genotyped pigs to inhibit viral entry and replication as quickly as the intact GBP5 protein of the AB genotyped pigs.
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http://dx.doi.org/10.1186/s12864-016-2547-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4782518PMC
March 2016

The Colonic Microbiome and Epithelial Transcriptome Are Altered in Rats Fed a High-Protein Diet Compared with a Normal-Protein Diet.

J Nutr 2016 Mar 3;146(3):474-83. Epub 2016 Feb 3.

Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, Laboratory of Gastrointestinal Microbiology, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China; and

Background: A high-protein diet (HPD) can produce hazardous compounds and reduce butyrate-producing bacteria in feces, which may be detrimental to gut health. However, information on whether HPD affects intestinal function is limited.

Objective: The aim of this study was to determine the impact of an HPD on the microbiota, microbial metabolites, and epithelial transcriptome in the colons of rats.

Methods: Adult male Wistar rats were fed either a normal-protein diet (20% protein, 56% carbohydrate) or an HPD (45% protein, 30% carbohydrate) for 6 wk (n = 10 rats per group, individually fed). After 6 wk, the colonic microbiome, microbial metabolites, and epithelial transcriptome were determined.

Results: Compared with the normal-protein diet, the HPD adversely altered the colonic microbiota by increasing (P < 0.05) Escherichia/Shigella, Enterococcus, Streptococcus, and sulfate-reducing bacteria by 54.9-fold, 31.3-fold, 5.36-fold, and 2.59-fold, respectively. However, the HPD reduced Ruminococcus (8.04-fold), Akkermansia (not detected in HPD group), and Faecalibacterium prausnitzii (3.5-fold) (P < 0.05), which are generally regarded as beneficial bacteria in the colon. Concomitant increases in cadaverine (4.88-fold), spermine (31.2-fold), and sulfide (4.8-fold) (P < 0.05) and a decrease in butyrate (2.16-fold) (P < 0.05) in the HPD rats indicated an evident shift toward the production of unhealthy microbial metabolites. In the colon epithelium of the HPD rats, transcriptome analysis identified an upregulation of genes (P < 0.05) involved in disease pathogenesis; these genes are involved in chemotaxis, the tumor necrosis factor signal process, and apoptosis. The HPD was also associated with a downregulation of many genes (P < 0.05) involved in immunoprotection, such as genes involved in innate immunity, O-linked glycosylation of mucin, and oxidative phosphorylation, suggesting there may be an increased disease risk in these rats. The abundance of Escherichia/Shigella, Enterococcus, and Streptococcus was positively correlated (Spearman's ρ > 0.7, P < 0.05) with genes and metabolites generally regarded as being involved in disease pathogenesis, suggesting these bacteria may mediate the detrimental effects of HPDs on colonic health.

Conclusion: Our findings suggest that the HPD altered the colonic microbial community, shifted the metabolic profile, and affected the host response in the colons of rats toward an increased risk of colonic disease.
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http://dx.doi.org/10.3945/jn.115.223990DOI Listing
March 2016

Identification of a putative quantitative trait nucleotide in guanylate binding protein 5 for host response to PRRS virus infection.

BMC Genomics 2015 May 28;16:412. Epub 2015 May 28.

Department of Animal Science, Iowa State University, 2255 Kildee Hall, Ames, IA, 50011, USA.

Background: Previously, we identified a major quantitative trait locus (QTL) for host response to Porcine Respiratory and Reproductive Syndrome virus (PRRSV) infection in high linkage disequilibrium (LD) with SNP rs80800372 on Sus scrofa chromosome 4 (SSC4).

Results: Within this QTL, guanylate binding protein 5 (GBP5) was differentially expressed (DE) (p < 0.05) in blood from AA versus AB rs80800372 genotyped pigs at 7,11, and 14 days post PRRSV infection. All variants within the GBP5 transcript in LD with rs80800372 exhibited allele specific expression (ASE) in AB individuals (p < 0.0001). A transcript re-assembly revealed three alternatively spliced transcripts for GBP5. An intronic SNP in GBP5, rs340943904, introduces a splice acceptor site that inserts five nucleotides into the transcript. Individuals homozygous for the unfavorable AA genotype predominantly produced this transcript, with a shifted reading frame and early stop codon that truncates the 88 C-terminal amino acids of the protein. RNA-seq analysis confirmed this SNP was associated with differential splicing by QTL genotype (p < 0.0001) and this was validated by quantitative capillary electrophoresis (p < 0.0001). The wild-type transcript was expressed at a higher level in AB versus AA individuals, whereas the five-nucleotide insertion transcript was the dominant form in AA individuals. Splicing and ASE results are consistent with the observed dominant nature of the favorable QTL allele. The rs340943904 SNP was also 100 % concordant with rs80800372 in a validation population that possessed an alternate form of the favorable B QTL haplotype.

Conclusions: GBP5 is known to play a role in inflammasome assembly during immune response. However, the role of GBP5 host genetic variation in viral immunity is novel. These findings demonstrate that rs340943904 is a strong candidate causal mutation for the SSC4 QTL that controls variation in host response to PRRSV.
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http://dx.doi.org/10.1186/s12864-015-1635-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4446061PMC
May 2015

Egg ovotransferrin-derived ACE inhibitory peptide IRW increases ACE2 but decreases proinflammatory genes expression in mesenteric artery of spontaneously hypertensive rats.

Mol Nutr Food Res 2015 Sep 26;59(9):1735-44. Epub 2015 Jun 26.

Department of Agricultural, Food and Nutritional Science, Faculty of Agricultural, Life and Environmental Sciences, University of Alberta, Edmonton, AB, Canada.

Scope: Egg ovotransferrin-derived angiotensin converting enzyme (ACE) inhibitory peptide IRW was previously shown to reduce blood pressure in spontaneously hypertensive rats through reduced vascular inflammation and increased nitric oxide-mediated vasorelaxation. The main objective of the present study was to investigate the molecular mechanism of this peptide through transcriptome analysis by RNAseq technique.

Methods And Results: Total RNA was extracted from kidney and mesenteric arteries; the RNAseq libraries (from untreated and IRW-treated groups) were constructed and subjected to sequence using HiSeq 2000 system (Illumina) system. A total of 12 764 and 13 352 genes were detected in kidney and mesenteric arteries, respectively. The differentially expressed (DE) genes between untreated and IRW-treated groups were identified and the functional analysis through ingenuity pathway analysis revealed a greater role of DE genes identified from mesenteric arteries than that of kidney in modulating various cardiovascular functions. Subsequent qPCR analysis further confirmed that IRW significantly increased the expression of ACE-2, ABCB-1, IRF-8, and CDH-1 while significantly decreased the expression ICAM-1 and VCAM-1 in mesenteric arteries.

Conclusion: Our research showed for the first time that ACE inhibitory peptide IRW could contribute to its antihypertensive activity through increased ACE2 and decreased proinflammatory genes expression.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5034750PMC
http://dx.doi.org/10.1002/mnfr.201500050DOI Listing
September 2015

Xylo-oligosaccharides and virginiamycin differentially modulate gut microbial composition in chickens.

Microbiome 2015 10;3:15. Epub 2015 Apr 10.

Department of Animal Science, McGill University, 21111 Lakeshore Road, Ste-Anne-De-Bellevue, Quebec Canada.

Background: The emergence and spread of antibiotic resistance in pathogens have led to a restriction on the use of antibiotic growth promoters (AGPs) in animal feed in some countries. The potential negative after-effects of a ban on AGPs could be mitigated by improving animal intestinal health with prebiotic dietary fibers such as xylo-oligosaccharides (XOS). However, the mechanism(s) by which an antibiotic or prebiotic contributes to the health and growth of animals are not well understood. Here, we evaluated XOS and virginiamycin (VIRG)-mediated changes in gut microbiota of broiler chickens using pyrosequencing of the 16S rRNA gene.

Results: There was a significant change in the relative abundance of certain bacteria, but the overall microbial diversity was not affected by treatment with either XOS or VIRG. Supplementation of HXOS (2 g XOS/kg diet) increased the proportion of Lactobacillus genus in the cecum, whereas Propionibacterium and Corynebacterium genera were enriched in the ileum of VIRG (16 mg/kg) treated birds. Furthermore, an increase in the cecal concentrations of acetate and propionate was observed in HXOS- and VIRG-fed chickens, respectively. These two groups of birds had better feed conversion efficiencies in comparison with the control group from day 7 to 21. In addition, temporal variations in the gut microbiota were evident in the chickens of different ages.

Conclusions: Treatments with XOS or VIRG modified the relative abundance but not the presence or absence of specific microbial genus. The increase in both Lactobacillus spp. and acetate production in the cecum of HXOS-treated chickens may promote intestinal health.
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http://dx.doi.org/10.1186/s40168-015-0079-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4396176PMC
April 2015

Perspectives on super-shedding of Escherichia coli O157:H7 by cattle.

Foodborne Pathog Dis 2015 Feb 16;12(2):89-103. Epub 2014 Dec 16.

1 Agriculture and Agri-Food Canada, Lethbridge Research Centre , Lethbridge, Alberta, Canada .

Escherichia coli O157:H7 is a foodborne pathogen that causes illness in humans worldwide. Cattle are the primary reservoir of this bacterium, with the concentration and frequency of E. coli O157:H7 shedding varying greatly among individuals. The term "super-shedder" has been applied to cattle that shed concentrations of E. coli O157:H7 ≥ 10⁴ colony-forming units/g feces. Super-shedders have been reported to have a substantial impact on the prevalence and transmission of E. coli O157:H7 in the environment. The specific factors responsible for super-shedding are unknown, but are presumably mediated by characteristics of the bacterium, animal host, and environment. Super-shedding is sporadic and inconsistent, suggesting that biofilms of E. coli O157:H7 colonizing the intestinal epithelium in cattle are intermittently released into feces. Phenotypic and genotypic differences have been noted in E. coli O157:H7 recovered from super-shedders as compared to low-shedding cattle, including differences in phage type (PT21/28), carbon utilization, degree of clonal relatedness, tir polymorphisms, and differences in the presence of stx2a and stx2c, as well as antiterminator Q gene alleles. There is also some evidence to support that the native fecal microbiome is distinct between super-shedders and low-shedders and that low-shedders have higher levels of lytic phage within feces. Consequently, conditions within the host may determine whether E. coli O157:H7 can proliferate sufficiently for the host to obtain super-shedding status. Targeting super-shedders for mitigation of E. coli O157:H7 has been proposed as a means of reducing the incidence and spread of this pathogen to the environment. If super-shedders could be easily identified, strategies such as bacteriophage therapy, probiotics, vaccination, or dietary inclusion of plant secondary compounds could be specifically targeted at this subpopulation. Evidence that super-shedder isolates share a commonality with isolates linked to human illness makes it imperative that the etiology of this phenomenon be characterized.
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http://dx.doi.org/10.1089/fpd.2014.1829DOI Listing
February 2015

In vitro evaluation of effects of gut region and fiber structure on the intestinal dominant bacterial diversity and functional bacterial species.

Anaerobe 2014 Aug 24;28:168-77. Epub 2014 Jun 24.

Key Laboratory for Agro-Ecological Processes in Subtropical Region, and South-Central Experimental Station of Animal Nutrition and Feed Science in Ministry of Agriculture, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha, Hunan 410125, PR China.

Understanding the intestinal bacteria in ruminants and their population kinetics is essential for their ecological function, as well as their interaction with the host. In this in vitro study, we aimed to determine whether gut region and fiber structure can influence bacterial diversity and functional bacterial population, together with the kinetics of functional bacterial species in the cecal inocula using PCR-DGGE and qPCR. A split plot design was conducted with gut regions (jejunum, ileum, cecum and colon) as main plot, and substrates (neutral detergent fiber (NDF) and cellulose (CEL)) as subplot. Incubation time and gut region affected dominant bacterial diversity. The numbers of total bacteria, cellulolytic bacteria, genus Prevotella and amylolytic bacteria in the hindgut inocula were greater (P < 0.05) than those in the small intestinal inocula. Fiber structure did not significantly influence the dominant bacterial diversity and the numbers of most examined functional bacterial species. The greatest increase rate of cellulolytic bacteria occurred earlier than amylolytic bacteria except for R. albus incubated with NDF. Changes in cellulolytic bacterial populations were not coordinative with alteration of fiber disappearance as well as CMCase and xylanase activities. All these suggest that the hindgut contents have greater potential to digest fiber than small intestinal contents, and cellulolytic bacteria are of significant value at the initial stage of fiber digestion among the fiber digestive microbes in the intestine.
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http://dx.doi.org/10.1016/j.anaerobe.2014.06.008DOI Listing
August 2014

Cellular and molecular implications of mature adipocyte dedifferentiation.

J Genomics 2013 15;1:5-12. Epub 2013 Oct 15.

2. Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA.

There is a voluminous amount of scientific literature dealing with the involvement of adipocytes in molecular regulation of carcass composition, obesity, metabolic syndrome, or diabetes. To form adipocytes (process termed adipogenesis) nearly all scientific papers refer to the use of preadipocytes, adipofibroblasts, stromal vascular cells or adipogenic cell lines, and their differentiation to form lipid-assimilating cells containing storage triacylglyceride. However, mature adipocytes, themselves, possess ability to undergo dedifferentiation, form proliferative-competent progeny cells (the exact plasticity is unknown) and reinitiate formation of cells capable of lipid metabolism and storage. The progeny cells would make a viable (and alternative) cell system for the evaluation of cell ability to reestablish lipid assimilation, ability to differentially express genes (as compared to other adipogenic cells), and to form other types of cells (multi-lineage potential). Understanding the dedifferentiation process itself and/or dedifferentiated fat cells could contribute to our knowledge of normal growth processes, or to disease function. Indeed, the ability of progeny cells to form other cell types could turn-out to be important for processes of tissue reconstruction/engineering and may have implications in clinical, biochemical or molecular processes.
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http://dx.doi.org/10.7150/jgen.3769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091435PMC
July 2014

Potential impact of mature adipocyte dedifferentiation in terms of cell numbers.

Int J Stem Cells 2011 Jun;4(1):76-8

Department of Animal Sciences, Washington State University, Pullman, WA 99164.

Mature adipocytes possess the capability to dedifferentiate and form proliferative-competent progeny cells. Little is currently known about the daughter cells, or the impact of such in vitro physiology in an in vivo situation, and the daughter cells may actually represent cells with stem-like cell potential. The present paper introduces implications of and impact of this physiology in terms of animal adiposity and composition.
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http://dx.doi.org/10.15283/ijsc.2011.4.1.76DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3840976PMC
June 2011

Lipid metabolism, adipocyte depot physiology and utilization of meat animals as experimental models for metabolic research.

Int J Biol Sci 2010 Nov 22;6(7):691-9. Epub 2010 Nov 22.

Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA.

Meat animals are unique as experimental models for both lipid metabolism and adipocyte studies because of their direct economic value for animal production. This paper discusses the principles that regulate adipogenesis in major meat animals (beef cattle, dairy cattle, and pigs), the definition of adipose depot-specific regulation of lipid metabolism or adipogenesis, and introduces the potential value of these animals as models for metabolic research including mammary biology and the ontogeny of fatty livers.
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http://dx.doi.org/10.7150/ijbs.6.691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990072PMC
November 2010

Skeletal muscle stem cells from animals I. Basic cell biology.

Int J Biol Sci 2010 Aug 31;6(5):465-74. Epub 2010 Aug 31.

Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA.

Skeletal muscle stem cells from food-producing animals are of interest to agricultural life scientists seeking to develop a better understanding of the molecular regulation of lean tissue (skeletal muscle protein hypertrophy) and intramuscular fat (marbling) development. Enhanced understanding of muscle stem cell biology and function is essential for developing technologies and strategies to augment the metabolic efficiency and muscle hypertrophy of growing animals potentially leading to greater efficiency and reduced environmental impacts of animal production, while concomitantly improving product uniformity and consumer acceptance and enjoyment of muscle foods.
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http://dx.doi.org/10.7150/ijbs.6.465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935669PMC
August 2010

Clonal Mature Adipocyte Production of Proliferative-competent Daughter Cells Requires Lipid Export Prior to Cell Division.

Int J Stem Cells 2009 May;2(1):76-9

Department of Animal Science, Washington State University, Pullman, WA 99164.

Background And Objectives: Numerous in vitro observations have been published to show that mature adipocytes may resume proliferation and begin to populate the adipofibroblast fraction or form other cell types.

Methods And Results: In the present study, we evaluated clonal cultures of mature pig-derived adipocytes as they began to reestablish their ability to divide. The lipid contained within the cytoplasm was either moved to the apical ends of the cell, or large droplets were physically extruded from the cell. In the latter case, we ascertained that the cell lipid droplet was handled in a different manner to that by beef-derived adipocytes as described in other published studies.

Conclusions: Pig-derived adipocytes expel large amounts of lipid directly into the medium environment prior to becoming capable of cell division, rather than retaining all lipids like the beef cells. This difference in lipid handling and trafficking may be a novel mechanism in adipocyte resumption of proliferation.
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http://dx.doi.org/10.15283/ijsc.2009.2.1.76DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4021797PMC
May 2009

The genome sequence of taurine cattle: a window to ruminant biology and evolution.

Science 2009 Apr;324(5926):522-8

To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
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http://dx.doi.org/10.1126/science.1169588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2943200PMC
April 2009

Probiotic preparation VSL#3 induces remission in children with mild to moderate acute ulcerative colitis: a pilot study.

Inflamm Bowel Dis 2009 May;15(5):760-8

Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, University of Alberta, Stollery Children's Hospital, Edmonton, Alberta, Canada.

Background: Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD) that has periods of exacerbated symptoms and periods that are symptom-free. The treatment of active UC with probiotic bacteria could possibly induce remission. We evaluated the clinical efficacy and safety profile of probiotic preparation VSL#3 in the treatment of mild to moderate acute UC in the pediatric population.

Methods: Eighteen eligible patients between the ages of 3-17 with mild to moderate acute UC received open-label VSL#3 daily in 2 divided doses for 8 weeks. The disease activity pre- and post-VSL#3 therapy was assessed by the simple clinical colitis activity index (SCCAI); Mayo ulcerative colitis endoscopic score; inflammatory markers: erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP); serum cytokine profiling; and rectal tissue microbial profiling done at baseline and at week 8.

Results: Thirteen patients completed 8 weeks of VSL#3 treatment and 5 patients were withdrawn due to lack of improvement. Remission (defined as SCCAI or=2, but final score
Conclusions: Treatment of pediatric patients diagnosed with mild to moderate UC with VSL#3 resulted in a remission rate of 56% and a combined remission/response rate of 61%.
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http://dx.doi.org/10.1002/ibd.20816DOI Listing
May 2009

Prevention of type 1 diabetes by immature dendritic cells treated with an ethanol extract of Paecilomyces hepiali Chen mycelium.

Methods Find Exp Clin Pharmacol 2008 Jul-Aug;30(6):421-9

Department of Pharmacology, Tongji Pharmaceutical College, HuaZhong University of Science and Technology, Wuhan, China.

Dendritic cells (DCs) classically promote immune responses but can be manipulated to induce antigen-specific hyporesponsiveness. It has been shown that phenotypically "immature" DCs, defined by low levels of costimulatory molecules at the cell surface, are involved in the induction of peripheral immune tolerance in autoimmunity. Paecilomyces hepiali Chen (PHC) mycelium, as a substitute for Cordyceps, has been used extensively as an immunomodulator to treat numerous diseases. In this study, the effects of an ethanol extract of PHC (EEPHC) on the phenotypic and functional maturation of bone marrow-derived DCs (BM-DCs) from NOD mice were evaluated. EEPHC significantly suppressed the expression of major histocompatibility complex (MHC) class II molecules and the costimulatory molecules CD40 and CD86 in NOD BM-DCs. These DCs also exhibited impaired production of the proinflammatory cytokine interleukin-12 (IL-12) and poor stimulatory capacity in the presence of EEPHC. Moreover, inhibition of the activation and differentiation of cultured DCs was associated with reduced DNA binding activity of nuclear factor kappa B (NF- kappaB), a transcription factor recently shown to be responsible for DC maturation. Administration of 3x10(5) EEPHC-treated DCs into NOD mice aged 3-4 weeks effectively prevented the onset of diabetes. Furthermore, splenocytes from the protected mice produced high amounts of IL-4 and IL-10 and low levels of IL-2 and interferon gamma, suggesting that these DCs deficient in NF- kappaB activity are responsible for the apparent shift in type 2 helper T cells. These novel results showed that EEPHC could specifically inhibit NF- kappaB activity and maintain DCs in a potentially tolerogenic state, permitting their use in strategies to induce immune tolerance in type 1 diabetes.
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http://dx.doi.org/10.1358/mf.2008.30.6.1186083DOI Listing
December 2008
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