Investigating the Reciprocal Interrelationships among the Ruminal Microbiota, Metabolome, and Mastitis in Early Lactating Holstein Dairy Cows

Simple Summary Dairy cow mastitis is an inflammatory disease often caused by bacterial infections. In the present study, we identified the ruminal microbial biomarkers and metabolites of mastitis in dairy cows. The investigation of the reciprocal interrelationships among the ruminal microbiota, metabolome, and mastitis revealed that short-chain fatty acid (SCFA)-producing microflora and the metabolites related to anti-inflammation and antibacterial activity were significantly higher in healthy cows than in those with mastitis. The identified potential species and metabolites might provide a novel perspective to assist in targeting the ruminal microbiota with preventive/therapeutic strategies against mastitis in the future. Abstract Mastitis in dairy cow significantly affects animal performance, ultimately reducing profitability. The reciprocal interrelationships among ruminal microbiota, metabolome, and mastitis combining early inflammatory factors (serum proinflammatory cytokines) in lactating dairy cows has not been explored, thus, this study evaluated these reciprocal interrelationships in early lactating Holstein dairy cows to identify potential microbial biomarkers and their relationship with ruminal metabolites. The ruminal fluid was sampled from 8 healthy and 8 mastitis cows for the microbiota and metabolite analyses. The critical ruminal microbial biomarkers and metabolites related to somatic cell counts (SCC) and serum proinflammatory cytokines were identified by the linear discriminant analysis effect size (LEfSe) algorithm and Spearman’s correlation analysis, respectively. The SCC level and proinflammatory cytokines positively correlated with Sharpea and negatively correlated with Ruminococcaceae UCG-014, Ruminococcus flavefaciens, and Treponema saccharophilum. Furthermore, the metabolites xanthurenic acid, and 1-(1H-benzo[d]imidazol-2-yl) ethan-1-ol positively correlated with microbial biomarkers of healthy cows, whereas, xanthine, pantothenic acid, and anacardic acid were negatively correlated with the microbial biomarkers of mastitis cows. In conclusion, Ruminococcus flavefaciens and Treponema saccharophilum are potential strains for improving the health of dairy cows. The current study provides a novel perspective to assist in targeting the ruminal microbiota with preventive/therapeutic strategies against inflammatory diseases in the future.

[1]  J. Xia,et al.  MetaboAnalyst 5.0: narrowing the gap between raw spectra and functional insights , 2021, Nucleic Acids Res..

[2]  Junhu Yao,et al.  Rumen microbiome structure and metabolites activity in dairy cows with clinical and subclinical mastitis , 2020, Journal of animal science and biotechnology.

[3]  Ming-Ju Chen,et al.  The Rumen Specific Bacteriome in Dry Dairy Cows and Its Possible Relationship with Phenotypes , 2020, Animals : an open access journal from MDPI.

[4]  J. Bromfield,et al.  Inflammatory diseases in dairy cows: Risk factors and associations with pregnancy after embryo transfer. , 2020, Journal of dairy science.

[5]  F. Peñagaricano,et al.  Long-term effects of postpartum clinical disease on milk production, reproduction, and culling of dairy cows. , 2019, Journal of dairy science.

[6]  Yunhe Fu,et al.  Targeting gut microbiota as a possible therapy for mastitis , 2019, European Journal of Clinical Microbiology & Infectious Diseases.

[7]  Yulong Yin,et al.  The impact of different levels of cysteine on the plasma metabolomics and intestinal microflora of sows from late pregnancy to lactation. , 2019, Food & function.

[8]  Jianxin Liu,et al.  Composition of Rumen Bacterial Community in Dairy Cows With Different Levels of Somatic Cell Counts , 2018, Front. Microbiol..

[9]  H. Barkema,et al.  Invited review: Microbiota of the bovine udder: Contributing factors and potential implications for udder health and mastitis susceptibility. , 2018, Journal of dairy science.

[10]  Heping Zhang,et al.  Cow-to-mouse fecal transplantations suggest intestinal microbiome as one cause of mastitis , 2018, Microbiome.

[11]  G. Foucras,et al.  A Critical Appraisal of Probiotics for Mastitis Control , 2018, Front. Vet. Sci..

[12]  G. Suen,et al.  Diet Influences Early Microbiota Development in Dairy Calves without Long-Term Impacts on Milk Production , 2018, Applied and Environmental Microbiology.

[13]  Yuhong Yang,et al.  Microbiome and butyrate production are altered in the gut of rats fed a glycated fish protein diet , 2018 .

[14]  Jianxin Liu,et al.  Assessment of Rumen Microbiota from a Large Dairy Cattle Cohort Reveals the Pan and Core Bacteriomes Contributing to Varied Phenotypes , 2018, Applied and Environmental Microbiology.

[15]  R. Cerri,et al.  Somatic cell count and type of intramammary infection impacts fertility from in vitro produced embryo transfer. , 2018, Theriogenology.

[16]  Yi Zhang,et al.  Dysbiosis Signatures of Gut Microbiota Along the Sequence from Healthy, Young Patients to Those with Overweight and Obesity , 2018, Obesity.

[17]  G. Suen,et al.  Assessing the impact of rumen microbial communities on methane emissions and production traits in Holstein cows in a tropical climate. , 2017, Systematic and applied microbiology.

[18]  Zhengtao Yang,et al.  Butyrate protects against disruption of the blood‐milk barrier and moderates inflammatory responses in a model of mastitis induced by lipopolysaccharide , 2017, British journal of pharmacology.

[19]  Weiyun Zhu,et al.  A High Grain Diet Dynamically Shifted the Composition of Mucosa-Associated Microbiota and Induced Mucosal Injuries in the Colon of Sheep , 2017, Front. Microbiol..

[20]  Y. Beckers,et al.  Illumina Sequencing Approach to Characterize Thiamine Metabolism Related Bacteria and the Impacts of Thiamine Supplementation on Ruminal Microbiota in Dairy Cows Fed High-Grain Diets , 2017, Front. Microbiol..

[21]  Yunhe Fu,et al.  Propionate Protects against Lipopolysaccharide-Induced Mastitis in Mice by Restoring Blood–Milk Barrier Disruption and Suppressing Inflammatory Response , 2017, Front. Immunol..

[22]  Hsuan-Cheng Huang,et al.  Bacterial Composition and Diversity in Breast Milk Samples from Mothers Living in Taiwan and Mainland China , 2017, Front. Microbiol..

[23]  Aleksandra A. Kolodziejczyk,et al.  Dysbiosis and the immune system , 2017, Nature Reviews Immunology.

[24]  L. Guan,et al.  Metatranscriptomic Profiling Reveals Linkages between the Active Rumen Microbiome and Feed Efficiency in Beef Cattle , 2017, Applied and Environmental Microbiology.

[25]  E. Khafipour,et al.  Changes in Microbiota in Rumen Digesta and Feces Due to a Grain-Based Subacute Ruminal Acidosis (SARA) Challenge , 2017, Microbial Ecology.

[26]  I. Tapio,et al.  The ruminal microbiome associated with methane emissions from ruminant livestock , 2017, Journal of Animal Science and Biotechnology.

[27]  H. Dai,et al.  Sodium Butyrate Ameliorates High-Concentrate Diet-Induced Inflammation in the Rumen Epithelium of Dairy Goats. , 2017, Journal of agricultural and food chemistry.

[28]  E. Rubin,et al.  Rumen metagenome and metatranscriptome analyses of low methane yield sheep reveals a Sharpea-enriched microbiome characterised by lactic acid formation and utilisation , 2016, Microbiome.

[29]  Y. Le Loir,et al.  Bovine Teat Microbiome Analysis Revealed Reduced Alpha Diversity and Significant Changes in Taxonomic Profiles in Quarters with a History of Mastitis , 2016, Front. Microbiol..

[30]  J. Santos,et al.  Carryover effect of postpartum inflammatory diseases on developmental biology and fertility in lactating dairy cows. , 2016, Journal of dairy science.

[31]  X. Xi,et al.  Bovine mastitis may be associated with the deprivation of gut Lactobacillus. , 2016, Beneficial microbes.

[32]  S. Türkyilmaz,et al.  Effects of Subclinical Mastitis on Serum Estradiol and Tumour Necrosis Factor Alpha Levels During Estrus in Dairy Cows , 2016 .

[33]  N. Al-Dhabi,et al.  A review of the immunomodulatory role of dietary tryptophan in livestock and poultry , 2016, Amino Acids.

[34]  D. Pitta,et al.  Associative patterns among anaerobic fungi, methanogenic archaea, and bacterial communities in response to changes in diet and age in the rumen of dairy cows , 2015, Front. Microbiol..

[35]  J. Gerber,et al.  Antibiotics, pediatric dysbiosis, and disease. , 2015, Cell host & microbe.

[36]  Itzhak Mizrahi,et al.  Potential Role of the Bovine Rumen Microbiome in Modulating Milk Composition and Feed Efficiency , 2014, PloS one.

[37]  Jiakun Wang,et al.  Pectin Induces an In Vitro Rumen Microbial Population Shift Attributed to the Pectinolytic Treponema Group , 2014, Current Microbiology.

[38]  L. Sordillo,et al.  TNFα Altered Inflammatory Responses, Impaired Health and Productivity, but Did Not Affect Glucose or Lipid Metabolism in Early-Lactation Dairy Cows , 2013, PloS one.

[39]  Robert C. Edgar,et al.  UPARSE: highly accurate OTU sequences from microbial amplicon reads , 2013, Nature Methods.

[40]  Pelin Yilmaz,et al.  The SILVA ribosomal RNA gene database project: improved data processing and web-based tools , 2012, Nucleic Acids Res..

[41]  Nicholas A. Bokulich,et al.  Quality-filtering vastly improves diversity estimates from Illumina amplicon sequencing , 2012, Nature Methods.

[42]  I. Mizrahi,et al.  Composition and Similarity of Bovine Rumen Microbiota across Individual Animals , 2012, PloS one.

[43]  S. Salzberg,et al.  FLASH: fast length adjustment of short reads to improve genome assemblies , 2011, Bioinform..

[44]  R. Zadoks,et al.  Molecular Epidemiology of Mastitis Pathogens of Dairy Cattle and Comparative Relevance to Humans , 2011, Journal of Mammary Gland Biology and Neoplasia.

[45]  C. Huttenhower,et al.  Metagenomic biomarker discovery and explanation , 2011, Genome Biology.

[46]  Rob Knight,et al.  UCHIME improves sensitivity and speed of chimera detection , 2011, Bioinform..

[47]  B. Haas,et al.  Chimeric 16S rRNA sequence formation and detection in Sanger and 454-pyrosequenced PCR amplicons. , 2011, Genome research.

[48]  K. Südekum,et al.  Pantothenic acid in ruminant nutrition: a review. , 2011, Journal of animal physiology and animal nutrition.

[49]  William A. Walters,et al.  QIIME allows analysis of high-throughput community sequencing data , 2010, Nature Methods.

[50]  G. Donofrio,et al.  Defining Postpartum Uterine Disease and the Mechanisms of Infection and Immunity in the Female Reproductive Tract in Cattle1 , 2009, Biology of reproduction.

[51]  M. Ngeleka,et al.  Mastitis caused by Bacillus anthracis in a beef cow. , 2008, The Canadian veterinary journal = La revue veterinaire canadienne.

[52]  M. Maes,et al.  The immune effects of TRYCATs (tryptophan catabolites along the IDO pathway): relevance for depression - and other conditions characterized by tryptophan depletion induced by inflammation. , 2007, Neuro endocrinology letters.

[53]  J. Tiedje,et al.  Naïve Bayesian Classifier for Rapid Assignment of rRNA Sequences into the New Bacterial Taxonomy , 2007, Applied and Environmental Microbiology.

[54]  H. Bartsch,et al.  Characterization of alkyl phenols in cashew (Anacardium occidentale) products and assay of their antioxidant capacity. , 2006, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[55]  P. Weimer Effects of dilution rate and pH on the ruminal cellulolytic bacterium Fibrobacter succinogenes S85 in cellulose-fed continuous culture , 2004, Archives of Microbiology.

[56]  R. P. Dinsmore,et al.  Use of systemic disease signs to assess disease severity in dairy cows with acute coliform mastitis. , 2001, Journal of the American Veterinary Medical Association.

[57]  I. Kubo,et al.  Antibacterial activity of anacardic acid and totarol, alone and in combination with methicillin, against methicillin-resistant Staphylococcus aureus. , 1996, The Journal of applied bacteriology.

[58]  I. Dohoo,et al.  Evaluation of changes in somatic cell counts as indicators of new intramammary infections , 1991 .

[59]  M. Wolin,et al.  Propionate Formation from Cellulose and Soluble Sugars by Combined Cultures of Bacteroides succinogenes and Selenomonas ruminantium , 1973 .