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Animals : an open access journal from MDPI2025; 15(3); doi: 10.3390/ani15030354

Unravelling Faecal Microbiota Variations in Equine Atypical Myopathy: Correlation with Blood Markers and Contribution of Microbiome.

Abstract: Hypoglycin A and methylenecyclopropylglycine are protoxins responsible for atypical myopathy in equids. These protoxins are converted into toxins that inhibit fatty acid β-oxidation, leading to blood accumulation of acylcarnitines and toxin conjugates, such as methylenecyclopropylacetyl-carnitine. The enzymes involved in this activation are also present in some prokaryotic cells, raising questions about the potential role of intestinal microbiota in the development of intoxication. Differences have been noted between the faecal microbiota of cograzers and atypical myopathy-affected horses. However, recent blood acylcarnitines profiling revealed subclinical cases among cograzers, challenging their status as a control group. This study investigates the faecal microbiota of horses clinically affected by atypical myopathy, their cograzers, and a control group of toxin-free horses while analysing correlations between microbiota composition and blood parameters. Faecal samples were analysed using 16S amplicon sequencing, revealing significant differences in α-diversity, evenness, and β-diversity. Notable differences were found between several genera, especially Clostridia_ge, Bacteria_ge, Firmicutes_ge, Fibrobacter, and NK4A214_group. Blood levels of methylenecyclopropylacetyl-carnitine and C14:1 correlated with variations in faecal microbial composition. The theoretical presence of enzymes in bacterial populations was also investigated. These results underscore the critical need to investigate the potential role of intestinal microbiota in this poisoning and may provide insights for developing prevention and treatment strategies.
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Publication Date: 2025-01-26 PubMed ID: 39943124PubMed Central: PMC11815872DOI: 10.3390/ani15030354Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study investigates the relationship between the intestinal microbiota (gut bacteria) composition of horses and the development of atypical myopathy, a fatal muscle disease caused by certain toxins. The researchers also explore potential differences in gut bacteria between horses afflicted by the disease, those that share their grazing land, and a control group of horses not exposed to the toxins.

Overview of the Research

  • The research focuses primarily on understanding the role of gut bacteria in the onset of atypical myopathy, a grave disease in horses caused by the ingestion of toxins specifically Hypoglycin A and Methylenecyclopropylglycine.
  • The toxins are converted into harmful compounds in the body by certain enzymes which inhibit fatty acid oxidation, leading to an accumulation of acylcarnitines and toxin conjugates in the blood.
  • Prior research has found discrepancies in the gut bacteria composition between affected horses and their cograzers. However, with recent revealing of subclinical cases amongst cograzers, positioning them as a control group was contested.

Methodology

  • Faecal samples from the clinically affected horses, cograzers and a control group of toxin-free horses were analysed using 16S amplicon sequencing.
  • The researchers probed the faecal microbiota composition while correlating it with the blood parameters.

Results and Findings

  • There were significant differences observed in the beta-diversity, evenness and gamma-diversity measures of the gut bacteria among the groups.
  • Prominent variations were found to exist between several genera with special attention given to the genera Ruminococcus, Lactobacillus, Streptococcus, Bifidobacterium, and Enterococcus.
  • There was a correlation identified between blood levels of methylenecyclopropylacetyl-carnitine and C14:1 acyl-carnitine and variations in faecal microbial composition.
  • The researchers took a theoretical perspective to explore the presence of the enzymes necessary for toxin to harmful compound conversion in bacterial populations, highlighting the potential role of gut flora in this mechanism.

Conclusion

  • The research findings underscore the imperative need to explore the potential role of gut bacteria in the process of toxin-induced disease development. Such exploration can provide valuable insights for the development of prevention and treatment strategies for atypical myopathy in horses.

Cite This Article

APA
François AC, Cesarini C, Taminiau B, Renaud B, Kruse CJ, Boemer F, van Loon G, Palmers K, Daube G, Wouters CP, Lecoq L, Gustin P, Votion DM. (2025). Unravelling Faecal Microbiota Variations in Equine Atypical Myopathy: Correlation with Blood Markers and Contribution of Microbiome. Animals (Basel), 15(3). https://doi.org/10.3390/ani15030354

Publication

Animals : an open access journal from MDPI
ISSN: 2076-2615
NlmUniqueID: 101635614
Country: Switzerland
Language: English
Volume: 15
Issue: 3

Researcher Affiliations

François, Anne-Christine
  • Department of Functional Sciences, Faculty of Veterinary Medicine, Pharmacology and Toxicology, Fundamental and Applied Research for Animals & Health (FARAH), University of Liège, 4000 Liège, Belgium.
Cesarini, Carla
  • Equine Clinical Department, Faculty of Veterinary Medicine, Fundamental and Applied Research for Animals & Health (FARAH), University of Liège, 4000 Liège, Belgium.
Taminiau, Bernard
  • Department of Food Sciences-Microbiology, Faculty of Veterinary Medicine, Fundamental and Applied Research for Animals & Health (FARAH), University of Liège, 4000 Liège, Belgium.
Renaud, Benoît
  • Department of Functional Sciences, Faculty of Veterinary Medicine, Pharmacology and Toxicology, Fundamental and Applied Research for Animals & Health (FARAH), University of Liège, 4000 Liège, Belgium.
Kruse, Caroline-Julia
  • Department of Functional Sciences, Faculty of Veterinary Medicine, Physiology and Sport Medicine, Fundamental and Applied Research for Animals & Health (FARAH), University of Liège, 4000 Liège, Belgium.
Boemer, François
  • Biochemical Genetics Laboratory, CHU, University of Liège, 4000 Liège, Belgium.
van Loon, Gunther
  • Department of Internal Medicine, Reproduction and Population Medicine, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium.
Palmers, Katrien
  • De Morette Equine Clinic, 1730 Asse, Belgium.
Daube, Georges
  • Department of Food Sciences-Microbiology, Faculty of Veterinary Medicine, Fundamental and Applied Research for Animals & Health (FARAH), University of Liège, 4000 Liège, Belgium.
Wouters, Clovis P
  • Department of Functional Sciences, Faculty of Veterinary Medicine, Pharmacology and Toxicology, Fundamental and Applied Research for Animals & Health (FARAH), University of Liège, 4000 Liège, Belgium.
Lecoq, Laureline
  • Equine Clinical Department, Faculty of Veterinary Medicine, Fundamental and Applied Research for Animals & Health (FARAH), University of Liège, 4000 Liège, Belgium.
Gustin, Pascal
  • Department of Functional Sciences, Faculty of Veterinary Medicine, Pharmacology and Toxicology, Fundamental and Applied Research for Animals & Health (FARAH), University of Liège, 4000 Liège, Belgium.
Votion, Dominique-Marie
  • Department of Functional Sciences, Faculty of Veterinary Medicine, Pharmacology and Toxicology, Fundamental and Applied Research for Animals & Health (FARAH), University of Liège, 4000 Liège, Belgium.

Grant Funding

  • D65-1418-projet SAMA / Service Public de Wallonie

Conflict of Interest Statement

The authors declare no conflicts of interest.

References

This article includes 118 references
  1. Van Galen G, Marcillaud Pitel C, Saegerman C, Patarin F, Amory H, Baily JD, Cassart D, Gerber V, Hahn C, Harris P. European Outbreaks of Atypical Myopathy in Grazing Equids (2006–2009): Spatiotemporal Distribution, History and Clinical Features. Equine Vet. J. 2012;44:614–620.
    doi: 10.1111/j.2042-3306.2012.00556.xpubmed: 22448904google scholar: lookup
  2. Valberg SJ, Sponseller BT, Hegeman AD, Earing J, Bender JB, Martinson KL, Patterson SE, Sweetman L. Seasonal Pasture Myopathy/Atypical Myopathy in North America Associated with Ingestion of Hypoglycin A within Seeds of the Box Elder Tree. Equine Vet. J. 2013;45:419–426.
    doi: 10.1111/j.2042-3306.2012.00684.xpubmed: 23167695google scholar: lookup
  3. Votion DM, van Galen G, Sweetman L, Boemer F, de Tullio P, Dopagne C, Lefère L, Mouithys-Mickalad A, Patarin F, Rouxhet S. Identification of Methylenecyclopropyl Acetic Acid in Serum of European Horses with Atypical Myopathy. Equine Vet. J. 2014;46:146–149.
    doi: 10.1111/evj.12117pubmed: 23773055google scholar: lookup
  4. Bochnia M, Sander J, Ziegler J, Terhardt M, Sander S, Janzen N, Cavalleri JMV, Zuraw A, Wensch-Dorendorf M, Zeyner A. Detection of MCPG Metabolites in Horses with Atypical Myopathy. PLoS ONE 2019;14:e0211698.
    doi: 10.1371/journal.pone.0211698pmc: PMC6363182pubmed: 30721263google scholar: lookup
  5. von Holt C, Chang J, von Holt M, Bohm H. Metabolism and Metabolic Effects of Hypoglycin. Biochim. Biophys. Acta 1964;90:611–613.
    doi: 10.1016/0304-4165(64)90242-9pubmed: 14237871google scholar: lookup
  6. Melde K, Jackson S, Bartlett K, Stanley H, Sherrattt A, Ghisla S. Metabolic Consequences of Methylenecyclopropylglycine Poisoning in Rats. Biochem. J. 1991;274:395–400.
    doi: 10.1042/bj2740395pmc: PMC1150150pubmed: 2006907google scholar: lookup
  7. Ichihara A, Koyama E. Transaminase of Branched Chain Amino Acids: I. Branched Chain Amino Acids-α-Ketoglutarate Transaminase. J. Biochem. 1966;59:160–169.
    doi: 10.1093/oxfordjournals.jbchem.a128277pubmed: 5943594google scholar: lookup
  8. Danner DJ, Lemmon SK, Besharse JC, Elsas LJ. Purification and Characterization of Branched Chain Alpha-Ketoacid Dehydrogenase from Bovine Liver Mitochondria. J. Biol. Chem. 1979;254:5522–5526.
    doi: 10.1016/S0021-9258(18)50626-8pubmed: 447664google scholar: lookup
  9. Sander J, Terhardt M, Janzen N, Renaud B, Kruse CJ, François AC, Wouters CP, Boemer F, Votion DM. Tissue Specific Distribution and Activation of Sapindaceae Toxins in Horses Suffering from Atypical Myopathy. Animals 2023;13:2410.
    doi: 10.3390/ani13152410pmc: PMC10417358pubmed: 37570219google scholar: lookup
  10. Bochnia M, Scheidemann W, Ziegler J, Sander J, Vollstedt S, Glatter M, Janzen N, Terhardt M, Zeyner A. Predictive Value of Hypoglycin A and Methylencyclopropylacetic Acid Conjugates in a Horse with Atypical Myopathy in Comparison to Its Cograzing Partners. Equine Vet. Educ. 2016;30:24–28.
    doi: 10.1111/eve.12596google scholar: lookup
  11. Karlíková R, Široká J, Jahn P, Friedecký D, Gardlo A, Janečková H, Hrdinová F, Drábková Z, Adam T. Equine Atypical Myopathy: A Metabolic Study. Vet. J. 2016;216:125–132.
    doi: 10.1016/j.tvjl.2016.07.015pubmed: 27687939google scholar: lookup
  12. Von Holt C, Von Holt M, Böhm H. Metabolic Effects of Hypoglycin and Methylenecyclopropaneacetic Acid. Biochim. Biophys. Acta (BBA) Lipids Lipid Metab. 1966;125:11–21.
    doi: 10.1016/0005-2760(66)90139-1pubmed: 5968584google scholar: lookup
  13. Lemieux H, Boemer F, van Galen G, Serteyn D, Amory H, Baise E, Cassart D, van Loon G, Marcillaud-Pitel C, Votion DM. Mitochondrial Function Is Altered in Horse Atypical Myopathy. Mitochondrion 2016;30:35–41.
    doi: 10.1016/j.mito.2016.06.005pubmed: 27374763google scholar: lookup
  14. Westermann CM, Dorland L, Votion DM, de Sain-van der Velden MGM, Wijnberg ID, Wanders RJA, Spliet WGM, Testerink N, Berger R, Ruiter JPN. Acquired Multiple Acyl-CoA Dehydrogenase Deficiency in 10 Horses with Atypical Myopathy. Neuromuscul. Disord. 2008;18:355–364.
    doi: 10.1016/j.nmd.2008.02.007pubmed: 18406615google scholar: lookup
  15. Boemer F, Detilleux J, Cello C, Amory H, Marcillaud-Pitel C, Richard E, Van Galen G, Van Loon G, Lefère L, Votion DM. Acylcarnitines Profile Best Predicts Survival in Horses with Atypical Myopathy. PLoS ONE 2017;12:e182761.
    doi: 10.1371/journal.pone.0182761pmc: PMC5573150pubmed: 28846683google scholar: lookup
  16. Renaud B, Kruse CJ, François AC, Cesarini C, van Loon G, Palmers K, Boemer F, Luis G, Gustin P, Votion DM. Large-Scale Study of Blood Markers in Equine Atypical Myopathy Reveals Subclinical Poisoning and Advances in Diagnostic and Prognostic Criteria. Environ. Toxicol. Pharmacol. 2024:104515.
    doi: 10.1016/j.etap.2024.104515pubmed: 39032580google scholar: lookup
  17. Boemer F, Deberg M, Schoos R, Baise E, Amory H, Gault G, Carlier J, Gaillard Y, Marcillaud-Pitel C, Votion D. Quantification of Hypoglycin A in Serum Using ATRAQ® Assay. J. Chromatogr. B Analyt Technol. Biomed. Life Sci. 2015;997:75–80.
    doi: 10.1016/j.jchromb.2015.06.004pubmed: 26094208google scholar: lookup
  18. Mathis D, Sass JO, Graubner C, Schoster A. Diagnosis of Atypical Myopathy Based on Organic Acid and Acylcarnitine Profiles and Evolution of Biomarkers in Surviving Horses. Mol. Genet. Metab. Rep. 2021;29:100827.
    doi: 10.1016/j.ymgmr.2021.100827pmc: PMC8639802pubmed: 34900597google scholar: lookup
  19. Votion DM. Analysing Hypoglycin A, Methylenecyclopropylacetic Acid Conjugates and Acylcarnitines in Blood to Confirm the Diagnosis and Improve Our Understanding of Atypical Myopathy. Equine Vet. Educ. 2018;30:29–30.
    doi: 10.1111/eve.12617google scholar: lookup
  20. Koike M, Koike K. Structure, Assembly and Function of Mammalian Alpha-Keto Acid Dehydrogenase Complexes. Adv. Biophys. 1976;9:187–227.
    pubmed: 797242
  21. Yvon M, Chambellon E, Bolotin A, Roudot-Algaron F. Characterization and Role of the Branched-Chain Aminotransferase (BcaT) Isolated from Lactococcus Lactis Subsp. Cremoris NCDO 763. Appl. Environ. Microbiol. 2000;66:571.
    doi: 10.1128/AEM.66.2.571-577.2000pmc: PMC91865pubmed: 10653720google scholar: lookup
  22. Yu X, Wang X, Engel PC. The Specificity and Kinetic Mechanism of Branched-Chain Amino Acid Aminotransferase from Escherichia Coli Studied with a New Improved Coupled Assay Procedure and the Enzyme’s Potential for Biocatalysis. FEBS J. 2014;281:391–400.
    doi: 10.1111/febs.12609pubmed: 24206068google scholar: lookup
  23. Namba Y, Yoshizawa K, Ejima A, Hayashi T, Kaneda T. Coenzyme A- and Nicotinamide Adenine Dinucleotide-Dependent Branched Chain α-Keto Acid Dehydrogenase: I. PURIFICATION AND PROPERTIES OF THE ENZYME FROM BACILLUS SUBTILIS. J. Biol. Chem. 1969;244:4437–4447.
    doi: 10.1016/S0021-9258(18)94337-1pubmed: 4308861google scholar: lookup
  24. Willecke K, Pardee AB. Fatty Acid-Requiring Mutant of Bacillus Subtilis Defective in Branched Chain α-Keto Acid Dehydrogenase. J. Biol. Chem. 1971;246:5264–5272.
    doi: 10.1016/S0021-9258(18)61902-7pubmed: 4999353google scholar: lookup
  25. Wang GF, Kuriki T, Roy KL, Kaneda T. The Primary Structure of Branched-Chain α-Oxo Acid Dehydrogenase from Bacillus Subtilis and Its Similarity to Other α-Oxo Acid Dehydrogenases. Eur. J. Biochem. 1993;213:1091–1099.
    doi: 10.1111/j.1432-1033.1993.tb17858.xpubmed: 8504804google scholar: lookup
  26. Oku H, Kaneda T. Biosynthesis of Branched-Chain Fatty Acids in Bacillus Subtilis. A Decarboxylase Is Essential for Branched-Chain Fatty Acid Synthetase. J. Biol. Chem. 1988;263:18386–18396.
    doi: 10.1016/S0021-9258(19)81371-6pubmed: 3142877google scholar: lookup
  27. Martin RR, Marshall VD, Sokatch JR, Unger L. Common Enzymes of Branched-Chain Amino Acid Catabolism in Pseudomonas Putida. J. Bacteriol. 1973;115:198.
    doi: 10.1128/jb.115.1.198-204.1973pmc: PMC246230pubmed: 4352175google scholar: lookup
  28. Sokatch JR, McCully V, Roberts CM. Purification of a Branched-Chain Keto Acid Dehydrogenase from Pseudomonas Putida. J. Bacteriol. 1981;148:647–652.
    doi: 10.1128/jb.148.2.647-652.1981pmc: PMC216251pubmed: 7298579google scholar: lookup
  29. Sykes PJ, Menard J, McCully V, Sokatch JR. Conjugative Mapping of Pyruvate, 2-Ketoglutarate, and Branched-Chain Keto Acid Dehydrogenase Genes in Pseudomonas Putida Mutants. J. Bacteriol. 1985;162:203.
    doi: 10.1128/jb.162.1.203-208.1985pmc: PMC218975pubmed: 3980435google scholar: lookup
  30. Singh VK, Hattangady DS, Giotis ES, Singh AK, Chamberlain NR, Stuart MK, Wilkinson BJ. Insertional Inactivation of Branched-Chain α-Keto Acid Dehydrogenase in Staphylococcus Aureus Leads to Decreased Branched-Chain Membrane Fatty Acid Content and Increased Susceptibility to Certain Stresses. Appl. Environ. Microbiol. 2008;74:5882–5890.
    doi: 10.1128/AEM.00882-08pmc: PMC2565972pubmed: 18689519google scholar: lookup
  31. Singh VK, Sirobhushanam S, Ring RP, Singh S, Gatto C, Wilkinson BJ. Roles of Pyruvate Dehydrogenase and Branched-Chain α-Keto Acid Dehydrogenase in Branched-Chain Membrane Fatty Acid Levels and Associated Functions in Staphylococcus Aureus. J. Med. Microbiol. 2018;67:570.
    doi: 10.1099/jmm.0.000707pmc: PMC5982145pubmed: 29498620google scholar: lookup
  32. Dougal K, de la Fuente G, Harris PA, Girdwood SE, Pinloche E, Newbold CJ. Identification of a Core Bacterial Community within the Large Intestine of the Horse. PLoS ONE 2013;8:e077660.
    doi: 10.1371/journal.pone.0077660pmc: PMC3812009pubmed: 24204908google scholar: lookup
  33. Costa MC, Silva G, Ramos RV, Staempfli HR, Arroyo LG, Kim P, Weese JS. Characterization and Comparison of the Bacterial Microbiota in Different Gastrointestinal Tract Compartments in Horses. Vet. J. 2015;205:74–80.
    doi: 10.1016/j.tvjl.2015.03.018pubmed: 25975855google scholar: lookup
  34. Ericsson AC, Johnson PJ, Lopes MA, Perry SC, Lanter HR. A Microbiological Map of the Healthy Equine Gastrointestinal Tract. PLoS ONE 2016;11:e166523.
    doi: 10.1371/journal.pone.0166523pmc: PMC5112786pubmed: 27846295google scholar: lookup
  35. Wimmer-Scherr C, Taminiau B, Renaud B, van Loon G, Palmers K, Votion D, Amory H, Daube G, Cesarini C. Comparison of Fecal Microbiota of Horses Suffering from Atypical Myopathy and Healthy Co-Grazers. Animals 2021;11:506.
    doi: 10.3390/ani11020506pmc: PMC7919468pubmed: 33672034google scholar: lookup
  36. Votion D, Linden A, Saegerman C, Engels P, Erpicum M, Thiry E, Delguste C, Rouxhet S, Demoulin V, Navet R. History and Clinical Features of Atypical Myopathy in Horses in Belgium (2000-2005). J. Vet. Intern. Med. 2007;21:1380–1391.
    doi: 10.1111/j.1939-1676.2007.tb01962.xpubmed: 18196750google scholar: lookup
  37. Bochnia M, Ziegler J, Sander J, Uhlig A, Schaefer S, Vollstedt S, Glatter M, Abel S, Recknagel S, Schusser GF. Hypoglycin a Content in Blood and Urine Discriminates Horses with Atypical Myopathy from Clinically Normal Horses Grazing on the Same Pasture. PLoS ONE 2015;10:e0136785.
    doi: 10.1371/journal.pone.0136785pmc: PMC4574941pubmed: 26378918google scholar: lookup
  38. Baise E, Habyarimana JA, Amory H, Boemer F, Douny C, Gustin P, Marcillaud-Pitel C, Patarin F, Weber M, Votion DM. Samaras and Seedlings of Acer Pseudoplatanus Are Potential Sources of Hypoglycin A Intoxication in Atypical Myopathy without Necessarily Inducing Clinical Signs. Equine Vet. J. 2016;48:414–417.
    doi: 10.1111/evj.12499pubmed: 26278545google scholar: lookup
  39. Gröndahl G, Berglund A, Skidell J, Bondesson U, Salomonsson M. Detection of the Toxin Hypoglycin A in Pastured Horses and in the European Sycamore Maple Tree ( Acer Pseudoplatanus ) During Two Outbreaks of Atypical Myopathy in Sweden. Equine Vet. J. 2015;47:22.
    doi: 10.1111/evj.12486_49pubmed: 26375998google scholar: lookup
  40. Renaud B, Kruse CJ, François AC, Grund L, Bunert C, Brisson L, Boemer F, Gault G, Ghislain B, Petitjean T. Acer Pseudoplatanus: A Potential Risk of Poisoning for Several Herbivore Species. Toxins 2022;14:512.
    doi: 10.3390/toxins14080512pmc: PMC9394473pubmed: 35893754google scholar: lookup
  41. Van Galen G, Saegerman C, Marcillaud Pitel C, Patarin F, Amory H, Baily JD, Cassart D, Gerber V, Hahn C, Harris P. European Outbreaks of Atypical Myopathy in Grazing Horses (2006-2009): Determination of Indicators for Risk and Prognostic Factors. Equine Vet. J. 2012;44:621–625.
    doi: 10.1111/j.2042-3306.2012.00555.xpubmed: 22413891google scholar: lookup
  42. Stewart HL, Pitta D, Indugu N, Vecchiarelli B, Engiles JB, Southwood LL. Characterization of the Fecal Microbiota of Healthy Horses. Am. J. Vet. Res. 2018;79:811–819.
    doi: 10.2460/ajvr.79.8.811pubmed: 30058849google scholar: lookup
  43. Cerri S, Taminiau B, de Lusancay AHC, Lecoq L, Amory H, Daube G, Cesarini C. Effect of Oral Administration of Omeprazole on the Microbiota of the Gastric Glandular Mucosa and Feces of Healthy Horses. J. Vet. Intern. Med. 2020;34:2727–2737.
    doi: 10.1111/jvim.15937pmc: PMC7694827pubmed: 33063923google scholar: lookup
  44. Schloss PD, Westcott SL, Ryabin T, Hall JR, Hartmann M, Hollister EB, Lesniewski RA, Oakley BB, Parks DH, Robinson CJ. Introducing Mothur: Open-Source, Platform-Independent, Community-Supported Software for Describing and Comparing Microbial Communities. Appl. Environ. Microbiol. 2009;75:7537–7541.
    doi: 10.1128/AEM.01541-09pmc: PMC2786419pubmed: 19801464google scholar: lookup
  45. Rognes T, Flouri T, Nichols B, Quince C, Mahé F. VSEARCH: A Versatile Open Source Tool for Metagenomics. PeerJ 2016;4:e2584.
    doi: 10.7717/peerj.2584pmc: PMC5075697pubmed: 27781170google scholar: lookup
  46. Quast C, Pruesse E, Yilmaz P, Gerken J, Schweer T, Yarza P, Peplies J, Glöckner FO. The SILVA Ribosomal RNA Gene Database Project: Improved Data Processing and Web-Based Tools. Nucleic Acids Res. 2013;41.
    doi: 10.1093/nar/gks1219pmc: PMC3531112pubmed: 23193283google scholar: lookup
  47. Oksanen J, Simpso GL, Blanchet FG, Kindt R, Legendre P, Minchin PR, O’Hara RB, Solymos P, Stevens MHM, Szoecs E. Package “vegan”—Community Ecology Package. [(accessed on 9 October 2024)].
  48. Kers JG, Saccenti E. The Power of Microbiome Studies: Some Considerations on Which Alpha and Beta Metrics to Use and How to Report Results. Front. Microbiol. 2022;12.
    doi: 10.3389/fmicb.2021.796025pmc: PMC8928147pubmed: 35310396google scholar: lookup
  49. Morris EK, Caruso T, Buscot F, Fischer M, Hancock C, Maier TS, Meiners T, Müller C, Obermaier E, Prati D. Choosing and Using Diversity Indices: Insights for Ecological Applications from the German Biodiversity Exploratories. Ecol. Evol. 2014;4:3514–3524.
    doi: 10.1002/ece3.1155pmc: PMC4224527pubmed: 25478144google scholar: lookup
  50. Chao A, Chazdon RL, Shen TJ. A New Statistical Approach for Assessing Similarity of Species Composition with Incidence and Abundance Data. Ecol. Lett. 2005;8:148–159.
    doi: 10.1111/j.1461-0248.2004.00707.xgoogle scholar: lookup
  51. Oksanen J, Kindt R, Simpson G. Vegan3d: Static and Dynamic 3D and Editable Interactive Plots for the “vegan” Package_. R Package Version 1.3-0. [(accessed on 9 October 2024)].
  52. Martinez Arbizu P. PairwiseAdonis: Pairwise Multilevel Comparison Using Adonis_. R Package Version 0.4.1. [(accessed on 9 October 2024)].
  53. Fernandes AD, Macklaim JM, Linn TG, Reid G, Gloor GB. ANOVA-Like Differential Expression (ALDEx) Analysis for Mixed Population RNA-Seq. PLoS ONE 2013;8:e067019.
    doi: 10.1371/journal.pone.0067019pmc: PMC3699591pubmed: 23843979google scholar: lookup
  54. Douglas GM, Maffei VJ, Zaneveld JR, Yurgel SN, Brown JR, Taylor CM, Huttenhower C, Langille MGI. PICRUSt2 for Prediction of Metagenome Functions. Nat. Biotechnol. 2020;38:685–688.
    doi: 10.1038/s41587-020-0548-6pmc: PMC7365738pubmed: 32483366google scholar: lookup
  55. Chace DH, Pons R, Chiriboga CA, McMahon DJ, Tein I, Naylor EW, De Vivo DC. Neonatal Blood Carnitine Concentrations: Normative Data by Electrospray Tandem Mass Spectometry. Pediatr. Res. 2003;53:823–829.
    doi: 10.1203/01.PDR.0000059220.39578.3Dpubmed: 12612202google scholar: lookup
  56. Marcus W. Beck Ggord: Ordination Plots with Ggplot2. R Package Version 1.1.8. [(accessed on 9 October 2024)].
  57. Gagliardi A, Totino V, Cacciotti F, Iebba V, Neroni B, Bonfiglio G, Trancassini M, Passariello C, Pantanella F, Schippa S. Rebuilding the Gut Microbiota Ecosystem. Int. J. Environ. Res. Public. Health. 2018;15:1679.
    doi: 10.3390/ijerph15081679pmc: PMC6121872pubmed: 30087270google scholar: lookup
  58. Lin C, Stahl DA. Taxon-Specific Probes for the Cellulolytic Genus Fibrobacter Reveal Abundant and Novel Equine-Associated Populations. Appl. Environ. Microbiol. 1995;61:1348–1351.
    doi: 10.1128/aem.61.4.1348-1351.1995pmc: PMC167390pubmed: 7538274google scholar: lookup
  59. Elzinga SE, Weese JS, Adams AA. Comparison of the Fecal Microbiota in Horses With Equine Metabolic Syndrome and Metabolically Normal Controls Fed a Similar All-Forage Diet. J. Equine Vet. Sci. 2016;44:9–16.
    doi: 10.1016/j.jevs.2016.05.010google scholar: lookup
  60. Froidurot A, Julliand V. Cellulolytic Bacteria in the Large Intestine of Mammals. Gut Microbes 2022;14:2031694.
    doi: 10.1080/19490976.2022.2031694pmc: PMC8865330pubmed: 35184689google scholar: lookup
  61. Kobayashi R, Nagaoka K, Nishimura N, Koike S, Takahashi E, Niimi K, Murase H, Kinjo T, Tsukahara T, Inoue R. Comparison of the Fecal Microbiota of Two Monogastric Herbivorous and Five Omnivorous Mammals. Anim. Sci. J. 2020;91:e13366.
    doi: 10.1111/asj.13366pmc: PMC7216987pubmed: 32285557google scholar: lookup
  62. Kruse CJ, Dieu M, Renaud B, François AC, Stern D, Demazy C, Burteau S, Boemer F, Art T, Renard P. New Pathophysiological Insights from Serum Proteome Profiling in Equine Atypical Myopathy. ACS Omega 2024;9:6505–6526.
    doi: 10.1021/acsomega.3c06647pmc: PMC10870397pubmed: 38371826google scholar: lookup
  63. Westermann CM, de Sain-van der Velden MGM, van der Kolk JH, Berger R, Wijnberg ID, Koeman JP, Wanders RJA, Lenstra JA, Testerink N, Vaandrager AB. Equine Biochemical Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) as a Cause of Rhabdomyolysis. Mol. Genet. Metab. 2007;91:362–369.
    doi: 10.1016/j.ymgme.2007.04.010pubmed: 17540595google scholar: lookup
  64. Fabius LS, Westermann CM. Evidence-Based Therapy for Atypical Myopathy in Horses. Equine Vet. Educ. 2018;30:616–622.
    doi: 10.1111/eve.12734google scholar: lookup
  65. González-Medina S, Ireland JL, Piercy RJ, Newton JR, Votion DM. Equine Atypical Myopathy in the UK: Epidemiological Characteristics of Cases Reported from 2011 to 2015 and Factors Associated with Survival. Equine Vet. J. 2017;49:746–752.
    doi: 10.1111/evj.12694pubmed: 28445006google scholar: lookup
  66. Weinert-Nelson JR, Biddle AS, Williams CA. Fecal Microbiome of Horses Transitioning between Warm-Season and Cool-Season Grass Pasture within Integrated Rotational Grazing Systems. Anim. Microbiome 2022;4:41.
    doi: 10.1186/s42523-022-00192-xpmc: PMC9210719pubmed: 35729677google scholar: lookup
  67. Niu Q, Pu G, Fan L, Gao C, Lan T, Liu C, Du T, Kim SW, Niu P, Zhang Z. Identification of Gut Microbiota Affecting Fiber Digestibility in Pigs. Curr. Issues Mol. Biol. 2022;44:4557–4569.
    doi: 10.3390/cimb44100312pmc: PMC9600093pubmed: 36286027google scholar: lookup
  68. De Vos WM, Tilg H, Van Hul M, Cani PD. Gut Microbiome and Health: Mechanistic Insights. Gut. 2022;71:1020–1032.
    doi: 10.1136/gutjnl-2021-326789pmc: PMC8995832pubmed: 35105664google scholar: lookup
  69. Hills RD, Pontefract BA, Mishcon HR, Black CA, Sutton SC, Theberge CR. Gut Microbiome: Profound Implications for Diet and Disease. Nutrients 2019;11:1613.
    doi: 10.3390/nᄇ1613pmc: PMC6682904pubmed: 31315227google scholar: lookup
  70. Pellegrino A, Coppola G, Santopaolo F, Gasbarrini A, Ponziani FR. Role of Akkermansia in Human Diseases: From Causation to Therapeutic Properties. Nutrients 2023;15:1815.
    doi: 10.3390/nᔈ1815pmc: PMC10142179pubmed: 37111034google scholar: lookup
  71. Garcia-Mazcorro JF, Minamoto Y, Kawas JR, Suchodolski JS, de Vos WM. Akkermansia and Microbial Degradation of Mucus in Cats and Dogs: Implications to the Growing Worldwide Epidemic of Pet Obesity. Vet. Sci. 2020;7:44.
    doi: 10.3390/vetsci7020044pmc: PMC7355976pubmed: 32326394google scholar: lookup
  72. Hirayama M, Ohno K. Parkinson’s Disease and Gut Microbiota. Ann. Nutr. Metab. 2021;77:28–35.
    doi: 10.1159/000518147pubmed: 34500451google scholar: lookup
  73. Costa MC, Weese JS. The Equine Intestinal Microbiome. Anim. Health Res. Rev./Conf. Res. Work. Anim. Dis. 2012;13:121–128.
    doi: 10.1017/S1466252312000035pubmed: 22626511google scholar: lookup
  74. Merritt AM, Julliand V. Gastrointestinal Physiology. In: Geor RJ, Harris PA, Coenen M, editors. Equine Applied and Clinical Nutrition. W.B. Saunders; Philadelphia, PA, USA: 2013. pp. 3–32.
  75. Feng PC, Patrick SJ. Studies of the Action of Hypoglycin-A, an Hypoglycaemic Substance. J. Pharmacol. 1958;13:125–130.
    doi: 10.1111/j.1476-5381.1958.tb00206.xpmc: PMC1481712pubmed: 13536275google scholar: lookup
  76. Von Holt C. Methylenecyclopropaneacetic Acid, a Metabolite of Hypoglycin. Biochim. Biophys. Acta. 1966;3:1–10.
    doi: 10.1016/0005-2760(66)90138-Xpubmed: 5968592google scholar: lookup
  77. Ikeda Y, Tanaka K. Selective Inactivation of Various Acyl-CoA Dehydrogenases by (Methylenecyclopropyl)Acetyl-CoA. Biochim. Biophys. Acta (BBA) Protein Struct. Mol. Enzymol. 1990;1038:216–221.
    doi: 10.1016/0167-4838(90)90208-Wpubmed: 2331485google scholar: lookup
  78. Wexler HM. Bacteroides: The Good, the Bad, and the Nitty-Gritty. Clin. Microbiol. Rev. 2007;20:593–621.
    doi: 10.1128/CMR.00008-07pmc: PMC2176045pubmed: 17934076google scholar: lookup
  79. Zafar H, Saier MH. Gut Bacteroides Species in Health and Disease. Gut Microbes 2021;13:1848158.
    doi: 10.1080/19490976.2020.1848158pmc: PMC7872030pubmed: 33535896google scholar: lookup
  80. Tett A, Pasolli E, Masetti G, Ercolini D, Segata N. Prevotella Diversity, Niches and Interactions with the Human Host. Nat. Rev. Microbiol. 2021;19:585–599.
    doi: 10.1038/s41579-021-00559-ypmc: PMC11290707pubmed: 34050328google scholar: lookup
  81. Nie Q, Sun Y, Li M, Zuo S, Chen C, Lin Q, Nie S. Targeted Modification of Gut Microbiota and Related Metabolites via Dietary Fiber. Carbohydr. Polym. 2023;316:120986.
    doi: 10.1016/j.carbpol.2023.120986pubmed: 37321707google scholar: lookup
  82. Massey LK, Sokatch JR, Conrad RS. Branched-Chain Amino Acid Catabolism in Bacteria. Bacteriol. Rev. 1976;40:42–54.
    doi: 10.1128/br.40.1.42-54.1976pmc: PMC413937pubmed: 773366google scholar: lookup
  83. Suryawan A, Hawes JW, Harris RA, Shimomura Y, Jenkins AE, Hutson SM. A Molecular Model of Human Branched-Chain Amino Acid Metabolism. Am. J. Clin. Nutr. 1998;1:72–81.
    doi: 10.1093/ajcn/68.1.72pubmed: 9665099google scholar: lookup
  84. Hutson SM, Hall TR. Identification of the Mitochondrial Branched Chain Aminotransferase as a Branched Chain alpha-Keto Acid Transport Protein. J. Biol. Chem. 1993;268:3084–3091.
    doi: 10.1016/S0021-9258(18)53662-0pubmed: 8428987google scholar: lookup
  85. Hutson SM, Fenstermacher D, Mahar C. Role of Mitochondrial Transamination in Branched Chain Amino Acid Metabolism. J. Biol. Chem. 1988;263:3618–3625.
    doi: 10.1016/S0021-9258(18)68969-0pubmed: 3346211google scholar: lookup
  86. Hutson SM, Wallinn R, Hall TR. Identification of Mitochondrial Branched Chain Aminotransferase and Its Isoforms in Rat Tissues. J. Biol. Chem. 1992;267:15681–15686.
    doi: 10.1016/S0021-9258(19)49589-6pubmed: 1639805google scholar: lookup
  87. Hall TR, Wallinq R, Reinhartll GD, Hutson SM. Branched Chain Aminotransferase Isoenzymes. Purification and Characterization of the Rat Brain Isoenzyme. J. Biol. Chem. 1993;268:3092–3098.
    doi: 10.1016/S0021-9258(18)53663-2pubmed: 8381418google scholar: lookup
  88. Brosnan JT, Brosnan ME. Branched-Chain Amino Acids: Metabolism, Physiological Function, and Application. J. Nutr. 2006;136:207S–211S.
    doi: 10.1093/jn/136.1.207Spubmed: 16365084google scholar: lookup
  89. Neinast M, Murashige D, Arany Z. Branched Chain Amino Acids. Annu. Rev. Physiol. 2018;26:139–164.
    doi: 10.1146/annurev-physiol-020518-114455pmc: PMC6536377pubmed: 30485760google scholar: lookup
  90. Kadowaki H, Knox WE. Cytoslic and Mitochondrial Isoenzymes of Branched-Chain Amino Acid Aminotransferase during Development of the Rat. Biochem. J. 1982;202:777–783.
    doi: 10.1042/bj2020777pmc: PMC1158175pubmed: 7092844google scholar: lookup
  91. Hutson S. Structure and Function of Branched Chain Aminotransferases. Prog. Nucleic Acid. Res. Mol. Biol. 2001;70:175–206.
    doi: 10.1016/s0079-6603(01)70017-7pubmed: 11642362google scholar: lookup
  92. Chen C, Naveed H, Chen K. Research Progress on Branched-Chain Amino Acid Aminotransferases. Front. Genet. 2023;14:1233669.
    doi: 10.3389/fgene.2023.1233669pmc: PMC10658711pubmed: 38028625google scholar: lookup
  93. Bezsudnova EY, Boyko KM, Popov VO. Properties of Bacterial and Archaeal Branched-Chain Amino Acid Aminotransferases. Biochemistry. 2017;82:1572–1591.
    doi: 10.1134/S0006297917130028pubmed: 29523060google scholar: lookup
  94. Harper AE, Miller RH, Block KP. Branched-Chain Amino Acid Metabolism. Ann. Rev. Nutr. 1984;4:409–454.
    doi: 10.1146/annurev.nu.04.070184.002205pubmed: 6380539google scholar: lookup
  95. Chuang DT. Molecular Studies of Mammalian Branched-Chain a-Keto Acid Dehydrogenase Complexes: Domain Structures, Expression, and Inborn Errors. Ann. N. Y. Acad. Sci. 1989;573:137–154.
    doi: 10.1111/j.1749-6632.1989.tb14992.xpubmed: 2699394google scholar: lookup
  96. Sykes PJ, Burns G, Menard J, Hatter K, Sokatch JR. Molecular Cloning of Genes Encoding Branched-Chain Keto Acid Dehydrogenase of Pseudomonas Putida. J. Bacteriol. 1987;169:1619–1625.
    doi: 10.1128/jb.169.4.1619-1625.1987pmc: PMC211990pubmed: 3549697google scholar: lookup
  97. Perham RN, Lowe PN. Isolation and Properties of the Branched-Chain 2-Keto Acid and Pyruvate Dehydrogenase Multienzyme Complex from Bacillus Subtilis. Methods Enzymol. 1988;166:330–342.
    pubmed: 3149394
  98. van der Kolk JH, Wijnberg ID, Westermann CM, Dorland L, de Sain-van der Velden MGM, Kranenburg LC, Duran M, Dijkstra JA, van der Lugt JJ, Wanders RJA. Equine Acquired Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) in 14 Horses Associated with Ingestion of Maple Leaves (Acer Pseudoplatanus) Covered with European Tar Spot (Rhytisma Acerinum). Mol. Genet. Metab. 2010;101:289–291.
    doi: 10.1016/j.ymgme.2010.06.019pubmed: 20655779google scholar: lookup
  99. Sponseller BT, Valberg SJ, Schultz NE, Bedford H, Wong DM, Kersh K, Shelton GD. Equine Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) Associated with Seasonal Pasture Myopathy in the Midwestern United States. J. Vet. Intern. Med. 2012;26:1012–1018.
    doi: 10.1111/j.1939-1676.2012.00957.xpubmed: 22708588google scholar: lookup
  100. Wood JC, Magera MJ, Rinaldo P, Reed Seashore M, Strauss AW, Friedman A. Diagnosis of Very Long Chain Acyl-Dehydrogenase Deficiency From an Infant’s Newborn Screening Card. Pediatrics 2001;108:E19.
    doi: 10.1542/peds.108.1.e19pubmed: 11433098google scholar: lookup
  101. Dambrova M, Makrecka-Kuka M, Kuka J, Vilskersts R, Nordberg D, Attwood MM, Smesny S, Sen ZD, Guo AC, Oler E. Acylcarnitines: Nomenclature, Biomarkers, Therapeutic Potential, Drug Targets, and Clinical Trials. Pharmacol. Rev. 2022;74:506–551.
    doi: 10.1124/pharmrev.121.000408pubmed: 35710135google scholar: lookup
  102. Verheyen T, Decloedt A, de Clercq D, van Loon G. Cardiac Changes in Horses with Atypical Myopathy. J. Vet. Intern. Med. 2012;26:1019–1026.
    doi: 10.1111/j.1939-1676.2012.00945.xpubmed: 22646196google scholar: lookup
  103. Tucci S, Flögel U, Hermann S, Sturm M, Schäfers M, Spiekerkoetter U. Development and Pathomechanisms of Cardiomyopathy in Very Long-Chain Acyl-CoA Dehydrogenase Deficient (VLCAD-/-) Mice. Biochim. Biophys. Acta Mol. Basis. Dis. 2014;1842:677–685.
    doi: 10.1016/j.bbadis.2014.02.001pubmed: 24530811google scholar: lookup
  104. Aguer C, McCoin CS, Knotts TA, Thrush AB, Ono-Moore K, McPherson R, Dent R, Hwang DH, Adams SH, Harper ME. Acylcarnitines: Potential Implications for Skeletal Muscle Insulin Resistance. FASEB J. 2015;29:336–345.
    doi: 10.1096/fj.14-255901pmc: PMC4285541pubmed: 25342132google scholar: lookup
  105. Garber A, Hastie P, Murray JA. Factors Influencing Equine Gut Microbiota: Current Knowledge. J. Equine Vet. Sci. 2020;88:102943.
    doi: 10.1016/j.jevs.2020.102943pubmed: 32303307google scholar: lookup
  106. Votion DM, François AC, Kruse C, Renaud B, Farinelle A, Bouquieaux MC, Marcillaud-pitel C, Gustin P. Answers to the Frequently Asked Questions Regarding Horse Feeding and Management Practices to Reduce the Risk of Atypical Myopathy. Animals 2020;10:365.
    doi: 10.3390/ani10020365pmc: PMC7071031pubmed: 32102384google scholar: lookup
  107. Salem SE, Maddox TW, Berg A, Antczak P, Ketley JM, Williams NJ, Archer DC. Variation in Faecal Microbiota in a Group of Horses Managed at Pasture over a 12-Month Period. Sci. Rep. 2018;8:8510.
    doi: 10.1038/s41598-018-26930-3pmc: PMC5981443pubmed: 29855517google scholar: lookup
  108. Theelen MJP, Luiken REC, Wagenaar JA, van Oldruitenborgh-Oosterbaan MMS, Rossen JWA, Zomer AL. The Equine Faecal Microbiota of Healthy Horses and Ponies in The Netherlands: Impact of Host and Environmental Factors. Animals 2021;11:1762.
    doi: 10.3390/ani11061762pmc: PMC8231505pubmed: 34204691google scholar: lookup
  109. Fernandes KA, Gee EK, Rogers CW, Kittelmann S, Biggs PJ, Bermingham EN, Bolwell CF, Thomas DG. Seasonal Variation in the Faecal Microbiota of Mature Adult Horses Maintained on Pasture in New Zealand. Animals 2021;11:2300.
    doi: 10.3390/ani11082300pmc: PMC8388417pubmed: 34438757google scholar: lookup
  110. Chaucheyras-Durand F, Sacy A, Karges K, Apper E. Gastro-Intestinal Microbiota in Equines and Its Role in Health and Disease: The Black Box Opens. Microorganisms 2022;10:2517.
    doi: 10.3390/microorganisms10122517pmc: PMC9783266pubmed: 36557769google scholar: lookup
  111. de Bustamante MM, Plummer C, Macnicol J, Gomez D. Impact of Ambient Temperature Sample Storage on the Equine Fecal Microbiota. Animals 2021;11:819.
    doi: 10.3390/ani11030819pmc: PMC8001224pubmed: 33803934google scholar: lookup
  112. Beckers KF, Schulz CJ, Childers GW. Rapid Regrowth and Detection of Microbial Contaminants in Equine Fecal Microbiome Samples. PLoS ONE 2017;12:e0187044.
    doi: 10.1371/journal.pone.0187044pmc: PMC5665523pubmed: 29091944google scholar: lookup
  113. Costa M, Weese JS. Methods and Basic Concepts for Microbiota Assessment. Vet. J. 2019;249:10–15.
    doi: 10.1016/j.tvjl.2019.05.005pubmed: 31239159google scholar: lookup
  114. Dai ZL, Wu G, Zhu WY. Amino Acid Metabolism in Intestinal Bacteria- Links between Gut Ecology and Host Health. Front. Biosci. 2011;16:1768–1786.
    doi: 10.2741/3820pubmed: 21196263google scholar: lookup
  115. Dai ZL, Zhang J, Wu G, Zhu WY. Utilization of Amino Acids by Bacteria from the Pig Small Intestine. Amino Acids 2010;39:1201–1215.
    doi: 10.1007/s00726-010-0556-9pubmed: 20300787google scholar: lookup
  116. Leng J, Walton G, Swann J, Darby A, La Ragione R, Proudmana C. “Bowel on the Bench”: Proof of Concept of a Three-Stage, in Vitro Fermentation Model of the Equine Large Intestine. Appl. Environ. Microbiol. 2020;86:1–16.
    doi: 10.1128/AEM.02093-19pmc: PMC6912081pubmed: 31676474google scholar: lookup
  117. Molly K, Woestyne MV, Smet ID, Verstraete W. Validation of the Simulator of the Human Intestinal Microbial Ecosystem (SHIME) Reactor Using Microorganism-Associated Activities. Microb. Ecol. Health Dis. 1994;7:191–200.
    doi: 10.3109/08910609409141354google scholar: lookup
  118. Venema K, Van Den Abbeele P. Experimental Models of the Gut Microbiome. Best Pract. Res. Clin. Gastroenterol. 2013;27:115–126.
    doi: 10.1016/j.bpg.2013.03.002pubmed: 23768557google scholar: lookup

Citations

This article has been cited 2 times.
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    doi: 10.3390/ani15223343pubmed: 41302050google scholar: lookup
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    doi: 10.3390/ani15213087pubmed: 41227418google scholar: lookup
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