Microbiome–metabolome analysis reveals unhealthy alterations in the composition and metabolism of ruminal microbiota with increasing dietary grain in a goat model
Abstract
Currently, knowledge about the impact of high-grain (HG) feeding on rumen microbiota and metabolome is limited. In this study, a combination of the 454 pyrosequencing strategy and the mass spectrometry-based metabolomics technique was applied to investigate the effects of increased dietary grain (0%, 25% and 50% maize grain) on changes in whole ruminal microbiota and their metabolites using goat as a ruminant model. We observed a significant influence of HG feeding in shaping the ruminal bacterial community structure, diversity and composition, with an overall dominance of bacteria of the phylum Firmicutes along with a low abundance of Bacteriodetes in the HG group. High-grain feeding increased the number of ciliate and methanogens, and decreased the density of anaerobic fungi and the richness of the archaeal community. The metabolomics analysis revealed that HG feeding increased the levels of several toxic, inflammatory and unnatural compounds, including endotoxin, tryptamine, tyramine, histamine and phenylacetate. Correlation analysis on the combined datasets revealed some potential relationships between ruminal metabolites and certain microbial species. Information about these relationships may prove useful in either direct (therapeutic) or indirect (dietary) interventions for ruminal disorders due to microbial compositional shifts, such as ruminal acidosis.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
There are few studies to date combining both sequencing and metabolomics to provide a more comprehensive analysis of the rumen system.
“However, there are few studies to date combining both sequencing and metabolomics to provide a more comprehensive analysis of the rumen system that would contribute information regarding metabolic expression of the genetic potential of the microbiota (Mao et al., 2016; Zhang J. et al., 2017; O'callaghan et al., 2018).”
From Addressing global ruminant agricultural challenges through understanding the rumen microbiome: past, present, and future (2018) · cites this paper as Mao et al., 2016
Cites
Schloss, P. D., Westcott, S. L., Ryabin, T., Hall, J. R., Hartmann, M., Hollister, E. B., Lesniewski, R. A., Oakley, B. B., Parks, D. H., Robinson, C. J., et al. (2009) · Applied and Environmental Microbiology · doi:10.1128/aem.01541-09 · Cited by 20,966 · see citing works
Search and clustering orders of magnitude faster than BLAST
Edgar, R. C. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq461 · Cited by 20,617 · see citing works
Naive Bayesian Classifier for Rapid Assignment of rRNA Sequences into the New Bacterial Taxonomy
Wang, Q., Garrity, G. M., Tiedje, J. M., & Cole, J. R. (2007) · Applied and Environmental Microbiology · doi:10.1128/aem.00062-07 · Cited by 19,770 · see citing works
UniFrac: a New Phylogenetic Method for Comparing Microbial Communities
Lozupone, C., & Knight, R. (2005) · Applied and Environmental Microbiology · doi:10.1128/aem.71.12.8228-8235.2005 · Cited by 8,227 · see citing works
FastTree: Computing Large Minimum Evolution Trees with Profiles instead of a Distance Matrix
Price, M. N., Dehal, P. S., & Arkin, A. P. (2009) · Molecular Biology and Evolution · doi:10.1093/molbev/msp077 · Cited by 5,602 · see citing works
THE COLORIMETRIC DETERMINATION OF LACTIC ACID IN BIOLOGICAL MATERIAL
Barker, S. B., & Summerson, W. H. (1941) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)51379-x · Cited by 3,454 · see citing works
PyNAST: a flexible tool for aligning sequences to a template alignment
Caporaso, J. G., Bittinger, K. L., Bushman, F. D., DeSantis, T. Z., Andersen, G. L., & Knight, R. D. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp636 · Cited by 3,374 · see citing works
Owens, F. N., Secrist, D. S., Hill, W. J., & Gill, D. R. (1998) · Journal of Animal Science · doi:10.2527/1998.761275x · Cited by 1,385 · see citing works
Zoetendal, E. G., Akkermans, A. D. L., & de Vos, W. M. (1998) · Applied and Environmental Microbiology · doi:10.1128/aem.64.10.3854-3859.1998 · Cited by 1,360 · see citing works
Dowd, S. E., Callaway, T. R., Wolcott, R. D., Sun, Y., McKeehan, T., Hagevoort, R. G., & Edrington, T. S. (2008) · BMC Microbiology · doi:10.1186/1471-2180-8-125 · Cited by 1,121 · see citing works
Subacute ruminal acidosis in dairy cows: The physiological causes, incidence and consequences
Plaizier, J. C. B., Krause, D. O., Gozho, G. N., & McBride, B. W. (2008) · The Veterinary Journal · doi:10.1016/j.tvjl.2007.12.016 · Cited by 1,014 · see citing works
Bovine acidosis: Implications on laminitis
Nocek, J. E. (1997) · Journal of Dairy Science · doi:10.3168/jds.s0022-0302(97)76026-0 · Cited by 950 · see citing works
Ruminal Acidosis in Beef Cattle: The Current Microbiological and Nutritional Outlook
Nagaraja, T. G., & Titgemeyer, E. C. (2007) · Journal of Dairy Science · doi:10.3168/jds.2006-478 · Cited by 884 · see citing works
Invited Review: Pathology, Etiology, Prevention, and Treatment of Fatty Liver in Dairy Cows
Bobe, G., Young, J. W., & Beitz, D. C. (2004) · Journal of Dairy Science · doi:10.3168/jds.s0022-0302(04)73446-3 · Cited by 877 · see citing works
Zoetendal, E. G., von Wright, A., Vilpponen-Salmela, T., Ben-Amor, K., Akkermans, A. D. L., & de Vos, W. M. (2002) · Applied and Environmental Microbiology · doi:10.1128/aem.68.7.3401-3407.2002 · Cited by 868 · see citing works
Jenkins, T. C., Wallace, R. J., Moate, P. J., & Mosley, E. E. (2007) · Journal of Animal Science · doi:10.2527/jas.2007-0588 · Cited by 791 · see citing works
Microbial ecosystem and methanogenesis in ruminants
Morgavi, D. P., Forano, E., Martin, C., & Newbold, C. J. (2010) · animal · doi:10.1017/s1751731110000546 · Cited by 694 · see citing works
Diet-Dependent Shifts in the Bacterial Population of the Rumen Revealed with Real-Time PCR
Tajima, K., Aminov, R. I., Nagamine, T., Matsui, H., Nakamura, M., & Benno, Y. (2001) · Applied and Environmental Microbiology · doi:10.1128/aem.67.6.2766-2774.2001 · Cited by 681 · see citing works
Why are ruminal cellulolytic bacteria unable to digest cellulose at low pH?
Russell, J. B., & Wilson, D. B. (1996) · Journal of Dairy Science · doi:10.3168/jds.s0022-0302(96)76510-4 · Cited by 628 · see citing works
Composition and Similarity of Bovine Rumen Microbiota across Individual Animals
Jami, E., & Mizrahi, I. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033306 · Cited by 572 · see citing works
Khafipour, E., Krause, D. O., & Plaizier, J. C. B. (2009) · Journal of Dairy Science · doi:10.3168/jds.2008-1389 · Cited by 556 · see citing works
Rumen Microbiome Composition Determined Using Two Nutritional Models of Subacute Ruminal Acidosis
Khafipour, E., Li, S., Plaizier, J. C., & Krause, D. O. (2009) · Applied and Environmental Microbiology · doi:10.1128/aem.00739-09 · Cited by 520 · see citing works
Peng, L., He, Z., Chen, W., Holzman, I. R., & Lin, J. (2007) · Pediatric Research · doi:10.1203/01.pdr.0000250014.92242.f3 · Cited by 518 · see citing works
RUMINANT NUTRITION SYMPOSIUM: Role of fermentation acid absorption in the regulation of ruminal pH12
Aschenbach, J. R., Penner, G. B., Stumpff, F., & Gäbel, G. (2010) · Journal of Animal Science · doi:10.2527/jas.2010-3301 · Cited by 500 · see citing works
Microbial butyrate and its role for barrier function in the gastrointestinal tract
Plöger, S., Stumpff, F., Penner, G. B., Schulzke, J., Gäbel, G., Märtens, H., Shen, Z., Günzel, D., & Aschenbach, J. R. (2012) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2012.06553.x · Cited by 445 · see citing works
Status of the phylogenetic diversity census of ruminal microbiomes
Kim, M., Morrison, M., & Yu, Z. (2011) · FEMS Microbiology Ecology · doi:10.1111/j.1574-6941.2010.01029.x · Cited by 407 · see citing works
Kittelmann, S., Seedorf, H., Walters, W. A., Clemente, J. C., Knight, R. D., Gordon, J. I., & Janssen, P. H. (2013) · PLoS ONE · doi:10.1371/journal.pone.0047879 · Cited by 384 · see citing works
Community structures of fecal bacteria in cattle from different animal feeding operations
Shanks, O. C., Kelty, C. A., Archibeque, S., Jenkins, M., Newton, R. J., McLellan, S. L., Huse, S. M., & Sogin, M. L. (2011) · Applied and Environmental Microbiology · doi:10.1128/aem.02988-10 · Cited by 359 · see citing works
RUMINANT NUTRITION SYMPOSIUM: Molecular adaptation of ruminal epithelia to highly fermentable diets1
Penner, G. B., Steele, M. A., Aschenbach, J. R., & McBride, B. W. (2010) · Journal of Animal Science · doi:10.2527/jas.2010-3378 · Cited by 272 · see citing works
Zened, A., Combes, S., Cauquil, L., Mariette, J., Klopp, C., Bouchez, O., Meynadier, A., & Enjalbert, F. (2012) · FEMS Microbiology Ecology · doi:10.1111/1574-6941.12011 · Cited by 271 · see citing works
Substrate Preferences in Rumen Bacteria: Evidence of Catabolite Regulatory Mechanisms
Russell, J. B., & Baldwin, R. L. (1978) · Applied and Environmental Microbiology · doi:10.1128/aem.36.2.319-329.1978 · Cited by 254 · see citing works
A metabolomics approach to uncover the effects of grain diets on rumen health in dairy cows
Saleem, F., Ametaj, B. N., Bouatra, S., Mandal, R., Zebeli, Q., Dunn, S. M., & Wishart, D. S. (2012) · Journal of Dairy Science · doi:10.3168/jds.2012-5403 · Cited by 234 · see citing works
Khafipour, E., Krause, D. O., & Plaizier, J. C. B. (2009) · Journal of Dairy Science · doi:10.3168/jds.2008-1656 · Cited by 223 · see citing works
Adaptation of beef cattle to high-concentrate diets: Performance and ruminal metabolism1
Brown, M. S., Ponce, C. H., & Pulikanti, R. (2006) · Journal of Animal Science · doi:10.2527/2006.8413_supple25x · Cited by 215 · see citing works
Pinloche, E., McEwan, N. R., Marden, J. P., Bayourthe, C., Auclair, E., & Newbold, C. J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0067824 · Cited by 205 · see citing works
A high-grain diet causes massive disruption of ruminal epithelial tight junctions in goats
Liu, J., Xu, T., Liu, Y., Zhu, W., & Mao, S. (2013) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00068.2013 · Cited by 195 · see citing works
Self-citationMetabolism of chlorogenic acid by human plasma, liver, intestine and gut microflora
Plumb, G. W., García‐Conesa, M., Kroon, P. A., Rhodes, M. J. C., Ridley, S., & Williamson, G. (1999) · Journal of the Science of Food and Agriculture · doi:10.1002/(sici)1097-0010(19990301)79:3 · Cited by 189 · see citing works
Mao, S., Zhang, R., Wang, D., & Zhu, W. (2012) · BMC Veterinary Research · doi:10.1186/1746-6148-8-237 · Cited by 181 · see citing works
Self-citationDigestion and Absorption of Energy Substrates in the Lactating Cow
Sutton, J. D. (1985) · Journal of Dairy Science · doi:10.3168/jds.s0022-0302(85)81251-0 · Cited by 149 · see citing works
Lee, H., Jung, J. Y., Oh, Y. K., Lee, S., Madsen, E. L., & Jeon, C. O. (2012) · Applied and Environmental Microbiology · doi:10.1128/aem.00104-12 · Cited by 140 · see citing works
Harmon, D. L., Britton, R. A., Prior, R. L., & Stock, R. (1985) · Journal of Animal Science · doi:10.2527/jas1985.602560x · Cited by 137 · see citing works
The hydrogenation of unsaturated fatty acids in the ovine digestive tract
Ward, P., Scott, T., & Dawson, R. (1964) · Biochemical Journal · doi:10.1042/bj0920060 · Cited by 133 · see citing works
pH dynamics and bacterial community composition in the rumen of lactating dairy cows
Palmonari, A., Stevenson, D. M., Mertens, D. R., Cruywagen, C. W., & Weimer, P. J. (2010) · Journal of Dairy Science · doi:10.3168/jds.2009-2207 · Cited by 114 · see citing works
Metzler-Zebeli, B. U., Schmitz‐Esser, S., Klevenhusen, F., Podstatzky, L., Wagner, M., & Zebeli, Q. (2013) · Anaerobe · doi:10.1016/j.anaerobe.2013.02.005 · Cited by 107 · see citing works
The formation and metabolism of phenyl-substituted fatty acids in the ruminant
Scott, T., Ward, P., & Dawson, R. (1964) · Biochemical Journal · doi:10.1042/bj0900012 · Cited by 104 · see citing works
Gylswyk, N. O. V. (1990) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.1990.tb03948.x · Cited by 102 · see citing works
Relationship of Rumen Gram-Negative Bacteria and Free Endotoxin to Lactic Acidosis in Cattle
Nagaraja, T. G., Bartley, E. E., Fina, L. R., et al. (1978) · Journal of Animal Science · doi:10.2527/jas1978.4761329x · Cited by 96 · see citing works
Production of amines in equine cecal contents in an in vitro model of carbohydrate overload
Bailey, S. R., Rycroft, A. N., & Elliott, J. (2002) · Journal of Animal Science · doi:10.2527/2002.80102656x · Cited by 91 · see citing works
Nakazawa, F., Sato, M., Poco, S. E., et al. (2000) · INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY · doi:10.1099/00207713-50-2-679 · Cited by 88 · see citing works
Koetschan, C., Kittelmann, S., Lu, J., Al-Halbouni, D., Jarvis, G. N., Müller, T., Wolf, M., & Janssen, P. H. (2014) · PLoS ONE · doi:10.1371/journal.pone.0091928 · Cited by 80 · see citing works
Impact of nutrition on lameness and claw health in cattle
Lean, I. J., Westwood, C. T., Golder, H. M., & Vermunt, J. J. (2013) · Livestock Science · doi:10.1016/j.livsci.2013.06.006 · Cited by 78 · see citing works
Protozoa involved in butyric rather than lactic fermentative pattern during latent acidosis in sheep
Brossard, L., Martin, C., Chaucheyras‐Durand, F., & Michalet-Doreau, B. (2004) · annales de biologie animale biochimie biophysique · doi:10.1051/rnd:2004023 · Cited by 78 · see citing works
Effect of induction of subacute ruminal acidosis on milk fat profile and rumen parameters
Colman, E., Fokkink, W. B., Craninx, M., et al. (2010) · Journal of Dairy Science · doi:10.3168/jds.2010-3158 · Cited by 75 · see citing works
Klevenhusen, F., Hollmann, M., Podstatzky-Lichtenstein, L., et al. (2013) · Journal of Dairy Science · doi:10.3168/jds.2012-6187 · Cited by 72 · see citing works
Tymensen, L. D., Beauchemin, K. A., & McAllister, T. A. (2012) · Microbiology · doi:10.1099/mic.0.057984-0 · Cited by 69 · see citing works
Wang, D. S., Zhang, R. Y., Zhu, W., & Mao, S. (2013) · Livestock Science · doi:10.1016/j.livsci.2013.05.026 · Cited by 67 · see citing works
Self-citationMao, S., Zhang, G., & Zhu, W. (2007) · Animal Feed Science and Technology · doi:10.1016/j.anifeedsci.2007.04.001 · Cited by 65 · see citing works
Self-citationExperimental feed induction of ruminal lactic, propionic, or butyric acidosis in sheep1
Lettat, A., Nozière, P., Silberberg, M., et al. (2010) · Journal of Animal Science · doi:10.2527/jas.2010-2926 · Cited by 60 · see citing works
Backgrounding and finishing diets are associated with inflammatory responses in feedlot steers1
Ametaj, B. N., Koenig, K. M., Dunn, S. M., et al. (2008) · Journal of Animal Science · doi:10.2527/jas.2008-1196 · Cited by 51 · see citing works
Anaerobic fungi: Neocallimastigomycota
Griffith, G. W., Baker, S., Fliegerova, K. O., Liggenstoffer, A. S., van der Giezen, M., Voigt, K., & Beakes, G. W. (2010) · IMA Fungus · doi:10.5598/imafungus.2010.01.02.11 · Cited by 47 · see citing works
Su, Y., Bian, G., Zhu, Z., Smidt, H., & Zhu, W. (2014) · Archaea · doi:10.1155/2014/547908 · Cited by 44 · see citing works
Self-citationWells, J. E., & Russell, J. B. (1996) · Applied and Environmental Microbiology · doi:10.1128/aem.62.4.1342-1346.1996 · Cited by 43 · see citing works
Production of amines in equine cecal contents in an in vitro model of carbohydrate overload1
Bailey, S. R., Rycroft, A. N., & Elliott, J. (2002) · Journal of Animal Science · doi:10.1093/ansci/80.10.2656 · Cited by 30 · see citing works
Fusi, E., Rossi, L., Rebucci, R., Cheli, F., Giancamillo, A. D., Domeneghini, C., Pinotti, L., DELL’ORTO, V., & Baldi, A. (2003) · Small Ruminant Research · doi:10.1016/j.smallrumres.2003.07.009 · Cited by 27 · see citing works
Hydrogenation of Linoleic Acid by a Rumen Spirochete
Sachan, D. S., & Davis, C. L. (1969) · Journal of Bacteriology · doi:10.1128/jb.98.1.300-301.1969 · Cited by 25 · see citing works
Kristensen, S. (1974) · British Journal Of Nutrition · doi:10.1079/bjn19740044 · Cited by 23 · see citing works
Bañeras, L., Ros-Ponsatí, M., Cristina, X. P., et al. (2010) · FEMS Microbiology Ecology · doi:10.1111/j.1574-6941.2010.00895.x · Cited by 19 · see citing works
A, Y. G., & R, J. W. (2013) · African Journal of Microbiology Research · doi:10.5897/ajmr2013.5722 · Cited by 1 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Huws, S. A., Creevey, C. J., Oyama, L. B., Mizrahi, I., Denman, S. E., Popova, M., Muñoz-Tamayo, R., Forano, E., Waters, S. M., Hess, M., et al. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.02161 · Cited by 487 · see citing works
- Authors
- Mao, S., Huo, W., & Zhu, W.
- Affiliations
- Laboratory of Gastrointestinal Microbiology College of Animal Science and Technology Nanjing Agricultural University Nanjing 210095 Jiangsu China
- Venue
- Environmental Microbiology
- Publisher
- Wiley
- Published
- 2015-02-03
- Volume
- 18
- Issue
- 2
- Pages
- 525-541
- ISSN
- 1462-2912 (ISSN-L)
- 1462-2920
- OpenAlex
- W1723262713
- Cited by
- 257
- References
- 68
- Citations by year
- 2026: 15 · 2025: 15 · 2024: 20 · 2023: 15 · 2022: 30 · 2021: 37 · 2020: 41 · 2019: 24 · 2018: 25 · 2017: 20 · 2016: 12 · 2015: 3
- FWCI
- 23.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Environmental Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Key Basic Research Program of China (2011CB100801)
- Natural Science Foundation of China (NSFC) (31172228)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Agronomy and Crop Science › Ruminant Nutrition and Digestive Physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Nutrition and Physiology
- Keywords
- rumen microbiota, rumen metabolome, goats, maize grain, rumen ciliates, methanogenic archaea, anaerobic fungi, Firmicutes, Bacteroidetes, endotoxin, tryptamine, tyramine, histamine, phenylacetate, rumen acidosis
- MeSH terms
- Gastrointestinal Microbiome, Acidosis, Animals, Archaea, Bacteria, Edible Grain, Zea mays, Diet, Fungi, Goats, Rumen, Ciliophora, Metabolomics, Metabolome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
