In vitro ruminal fermentation and cow-to-mouse fecal transplantations verify the inter-relationship of microbiome and metabolome biomarkers: potential to promote health in dairy cows

There are differences in the gut microbiome and metabolome when the host undergoes different physical or pathological conditions. However, the inter-relationship of microbiome and metabolome biomarkers to potentially promote the health of dairy cows needs to be studied. Further, the development of next-generation probiotics for dairy cattle health promotion has not been demonstrated.In the present study, we identified the microbiome and metabolome biomarkers associated with healthy cows.We analyzed the relationships of the ruminal microorganism profile and metabolites between healthy and mastitis lactating dairy cows. The roles of bacterial biomarker were further verified by in vitro fermentation and cow-to-mouse fecal microbiota transplantation (FMT).Two species, Ruminococcus flavefaciens and Bifidobacterium longum subsp. longum, and six rumen metabolites were positively correlated with healthy cows by Spearman’s correlation analysis. Through in vitro ruminal fermentation, inoculating R. flavefaciens and B. longum subsp. longum showed the upregulation of the levels of putrescine, xanthurenic acid, and pyridoxal in the mastitis ruminal fluid, which confirmed the inter-relationships between these microbiota and metabolites associated with healthy cows. Further, we verified the role of R. flavefaciens and B. longum subsp. longum in promoting health by FMT. The administration of R. flavefaciens and B. longum subsp. longum reduced the death rate and recovered the bodyweight loss of germ-free mice caused by FMT mastitis feces.We provided evidence that the bacterial biomarkers alter downstream metabolites. This could indirectly indicate that the two bacterial biomarkers have the potential to be used as next-generation probiotics for dairy cattle, although it needs more evidence to support our hypothesis. Two species, R. flavefaciens and B. longum subsp. longum, with three metabolites, putrescine, xanthurenic acid, and pyridoxal, identified in the ruminal fluid, may point to a new health-promoting and disease-preventing approach for dairy cattle.

[1]  Yunhe Fu,et al.  Gut dysbiosis induces the development of mastitis through a reduction in host anti-inflammatory enzyme activity by endotoxemia , 2022, Microbiome.

[2]  Yunhe Fu,et al.  The Rumen Microbiota Contributes to the Development of Mastitis in Dairy Cows , 2022, Microbiology spectrum.

[3]  Shengguo Zhao,et al.  Ruminal bacterial community is associated with the variations of total milk solid content in Holstein lactating cows , 2022, Animal nutrition.

[4]  Cheng-Chih Hsu,et al.  Investigating the Reciprocal Interrelationships among the Ruminal Microbiota, Metabolome, and Mastitis in Early Lactating Holstein Dairy Cows , 2021, Animals : an Open Access Journal from MDPI.

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

[6]  G. Rocchetti,et al.  Application of metabolomics to assess milk quality and traceability , 2021 .

[7]  Shuli Yang,et al.  Host and altitude factors affect rumen bacteria in cattle , 2020, Brazilian Journal of Microbiology.

[8]  Xuan Chen,et al.  Effects of Gut Microbiome and Short-Chain Fatty Acids (SCFAs) on Finishing Weight of Meat Rabbits , 2020, Frontiers in Microbiology.

[9]  Yachun Wang,et al.  Glucose Metabolism and Dynamics of Facilitative Glucose Transporters (GLUTs) under the Influence of Heat Stress in Dairy Cattle , 2020, Metabolites.

[10]  A. Salem,et al.  Influence of dietary probiotic inclusion on growth performance, nutrient utilization, ruminal fermentation activities and methane production in growing lambs , 2020, Animal biotechnology.

[11]  W. Lu,et al.  The effect of a diet based on rice straw co-fermented with probiotics and enzymes versus a fresh corn Stover-based diet on the rumen bacterial community and metabolites of beef cattle , 2020, Scientific Reports.

[12]  F. Magne,et al.  The Firmicutes/Bacteroidetes Ratio: A Relevant Marker of Gut Dysbiosis in Obese Patients? , 2020, Nutrients.

[13]  T. Loh,et al.  Effects of postbiotic supplementation on growth performance, ruminal fermentation and microbial profile, blood metabolite and GHR, IGF-1 and MCT-1 gene expression in post-weaning lambs , 2019, BMC Veterinary Research.

[14]  Yong Zhu,et al.  Comparing the Microbial Community in Four Stomach of Dairy Cattle, Yellow Cattle and Three Yak Herds in Qinghai-Tibetan Plateau , 2019, Front. Microbiol..

[15]  B. Min,et al.  Potential role of rumen microbiota in altering average daily gain and feed efficiency in meat goats fed simple and mixed pastures using bacterial tag-encoded FLX amplicon pyrosequencing. , 2019, Journal of animal science.

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

[17]  T. Odamaki,et al.  Beneficial effects of Bifidobacterium longum subsp. longum BB536 on human health: Modulation of gut microbiome as the principal action , 2019, Journal of Functional Foods.

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

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

[20]  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.

[21]  Linshu Jiang,et al.  Illumina sequencing analysis of the ruminal microbiota in high-yield and low-yield lactating dairy cows , 2018, bioRxiv.

[22]  Yulong Yin,et al.  Impact of the Gut Microbiota on Intestinal Immunity Mediated by Tryptophan Metabolism , 2018, Front. Cell. Infect. Microbiol..

[23]  J. M. Larsen The immune response to Prevotella bacteria in chronic inflammatory disease. , 2017, Immunology.

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

[25]  C. Hill,et al.  Next-generation probiotics: the spectrum from probiotics to live biotherapeutics , 2017, Nature Microbiology.

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

[27]  K. Fliegerová,et al.  Analysis of the rumen bacterial diversity of goats during shift from forage to concentrate diet. , 2016, Anaerobe.

[28]  Shigeru Sato,et al.  Effects of a bacterial probiotic on ruminal pH and volatile fatty acids during subacute ruminal acidosis (SARA) in cattle , 2016, The Journal of veterinary medical science.

[29]  A. Cherdthong,et al.  Rumen microbes and microbial protein synthesis in Thai native beef cattle fed with feed blocks supplemented with a urea–calcium sulphate mixture , 2013, Archives of animal nutrition.

[30]  Jesse R. Zaneveld,et al.  Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences , 2013, Nature Biotechnology.

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

[32]  J. Holopainen,et al.  Milk haptoglobin, milk amyloid A, and N-acetyl-β-D-glucosaminidase activity in bovines with naturally occurring clinical mastitis diagnosed with a quantitative PCR test. , 2013, Journal of dairy science.

[33]  I. Mizrahi,et al.  Exploring the bovine rumen bacterial community from birth to adulthood , 2013, The ISME Journal.

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

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

[36]  D. Kenny,et al.  Effect of Phenotypic Residual Feed Intake and Dietary Forage Content on the Rumen Microbial Community of Beef Cattle , 2012, Applied and Environmental Microbiology.

[37]  A. Santos,et al.  Anti-inflammatory effects of purine nucleosides, adenosine and inosine, in a mouse model of pleurisy: evidence for the role of adenosine A2 receptors , 2012, Purinergic Signalling.

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

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

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

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

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

[43]  J. Doré,et al.  The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age , 2009, BMC Microbiology.

[44]  E. Khafipour,et al.  A grain-based subacute ruminal acidosis challenge causes translocation of lipopolysaccharide and triggers inflammation. , 2009, Journal of dairy science.

[45]  S. Naik,et al.  Polyamines: Potential anti-inflammatory agents and their possible mechanism of action , 2008, Indian journal of pharmacology.

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

[47]  R. Forster,et al.  Repeated ruminal dosing of Ruminococcus flavefaciens NJ along with a probiotic mixture in forage or concentrate-fed dairy cows: Effect on ruminal fermentation, cellulolytic populations and in sacco digestibility , 2007 .

[48]  Harry J Flint,et al.  Interactions and competition within the microbial community of the human colon: links between diet and health. , 2007, Environmental microbiology.

[49]  D. Beitz,et al.  Carbohydrate and lipid metabolism in farm animals. , 2007, The Journal of nutrition.

[50]  P. Weimer,et al.  Dominance of Prevotella and low abundance of classical ruminal bacterial species in the bovine rumen revealed by relative quantification real-time PCR , 2007, Applied Microbiology and Biotechnology.

[51]  G. Ghorbani,et al.  Effects of bacterial direct-fed microbials on ruminal fermentation, blood variables, and the microbial populations of feedlot cattle. , 2002, Journal of animal science.

[52]  H. Flint,et al.  The rumen microbial ecosystem--some recent developments. , 1997, Trends in microbiology.

[53]  G. Grant,et al.  Polyamines in food—implications for growth and health☆ , 1993 .

[54]  M. Kimura A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences , 1980, Journal of Molecular Evolution.

[55]  J. L. Mangan,et al.  The formation and distribution of methylamine in the ruminant digestive tract. , 1964, The Biochemical journal.

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

[57]  M. P. Bryant,et al.  Syntrophococcus sucromutans sp. nov. gen. nov. uses carbohydrates as electron donors and formate, methoxymonobenzenoids or Methanobrevibacter as electron acceptor systems , 2004, Archives of Microbiology.

[58]  F. Mcintosh,et al.  Natural Products as Manipulators of Rumen Fermentation , 2002 .

[59]  Kh Menke,et al.  Estimation of the energetic feed value obtained from chemical analysis and in vitro gas production using rumen fluid , 1988 .

[60]  R. E. Hungate CHAPTER IV – Ruminant Functions Related to Rumen Microbial Activity , 1966 .