Skip to main content
SpringerLink
Log in

The Effect of the Microbiota Metabolite—Butyric Acid on Motor Coordination, Muscle Strength and the Level of Oxidative Stress in Skeletal Muscles in Mice with Dysbiosis

  • Experimental Papers
  • Published:
Journal of Evolutionary Biochemistry and Physiology Aims and scope Submit manuscript

Abstract

According to modern concepts, the composition and diversity of the intestinal microbiota play an essential role in maintaining immunity, homeostasis, and, in general, the physiological functions of the host organism. Recently the positive role of the microbiota and its metabolites especially short-chain fatty acids, in the metabolism and functional activity of skeletal muscles was reported. The aim of our work was to analyze muscle strength and motor coordination in mice after injection of broad-spectrum antibiotics with simultaneous administration of a microbiota metabolite—one of the representatives of short-chain fatty acids—butyric acid. In addition, we determined the level of malondialdehyde, the concentration of total glutathione and the activity of glutathione peroxidases in the muscles of the hind limbs in mice with administration of antibiotics and butyric acid. The administration of antibiotics to adolescent mice for two weeks induced higher mortality and decrease of weight, and also caused significant changes in motor behavior, including an increase in horizontal motor activity, decrease in vertical motor activity, muscle strength, and motor coordination. A higher level of oxidative stress was found in the muscle tissues of the hind limbs of mice treated with antibiotics. At the same time, oral administration of butyric acid prevented the observed changes and improved not only behavioral disorders, but also partially reduced the level of oxidative stress. In conclusion, metabolite of normal microbiota has a positive effect on the functional and biochemical parameters of skeletal muscles in dysbiosis, which can be used to prevent loss of muscle function in various pathological conditions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.

REFERENCES

  1. Nay K, Jollet M, Goustard B, Baati N, Vernus B, Pontones M, Lefeuvre-Orfila L, Bendavid C, Rué O, Mariadassou M, Bonnieu A, Ollendorff V, Lepage P, Derbré F, Koechlin-Ramonatxo C (2019) Gut bacteria are critical for optimal muscle function: A potential link with glucose homeostasis. Am J Physiol Endocrinol Metab 317(1): E158–E171. https://doi.org/10.1152/ajpendo.00521.2018

    Article  CAS  PubMed  Google Scholar 

  2. Li G, Jin B, Fan Z (2022) Mechanisms Involved in Gut Microbiota Regulation of Skeletal Muscle. Oxid Med Cell Longev 2022: 151191. https://doi.org/10.1155/2022/2151191

    Article  CAS  Google Scholar 

  3. Sekirov I, Russell SL, Antunes LCM, Finlay BB (2010) Gut Microbiota in Health and Disease. Physiol Rev 90: 859–904. https://doi.org/10.1152/physrev.00045.2009

    Article  CAS  PubMed  Google Scholar 

  4. Evans WJ (2010) Skeletal muscle loss: cachexia, sarcopenia, and inactivity. Am J Clin Nutr 91(4): 1123S–1127S. https://doi.org/10.3945/ajcn.2010.28608A

    Article  CAS  PubMed  Google Scholar 

  5. Shaidullov IF, Sorokina DM, Sitdikov FG, Hermann A, Abdulkhakov SR, Sitdikova GF (2021) Short chain fatty acids and colon motility in a mouse model of irritable bowel syndrome. BMC Gastroenterol 21(1): 37. https://doi.org/10.1186/s12876-021-01613-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Inan MS, Rasoulpour RJ, Yin L, Hubbard AK, Rosenberg DW, Giardina C (2000) The luminal short-chain fatty acid butyrate modulates NF-kappaB activity in a human colonic epithelial cell line. Gastroenterology 118(4): 724–734. https://doi.org/10.1016/s0016-5085(00)70142-9

    Article  CAS  PubMed  Google Scholar 

  7. Arslanova A, Tarasova A, Alexandrova A, Novoselova V, Shaidullov I, Khusnutdinova D, Grigoryeva T, Yarullina D, Yakovleva O, Sitdikova G (2021) Protective effects of probiotics on cognitive and motor functions, anxiety level, visceral sensitivity, oxidative stress and microbiota in mice with antibiotic-induced dysbiosis. Life 11(8): 764. https://doi.org/10.3390/life11080764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Adamo KB, Graham TE (1998) Comparison of traditional measurements with macroglycogen and proglycogen analysis of muscle glycogen. J Appl Physiol 84(3): 908–913. https://doi.org/10.1152/jappl.1998.84.3.908

    Article  CAS  PubMed  Google Scholar 

  9. Dinan TG, Cryan JF (2017) Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration. J Physiol 595(2): 489–503. https://doi.org/10.1113/JP273106

    Article  CAS  PubMed  Google Scholar 

  10. Bäckhed F, Manchester JK, Semenkovich CF, Gordon JI (2007) Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci USA 104(3): 979–984. https://doi.org/10.1073/pnas.0605374104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Bindels LB, Delzenne NM (2013) Muscle wasting: the gut microbiota as a new therapeutic target? Int J Biochem Cell Biol 45(10): 2186–2190. https://doi.org/10.1016/j.biocel.2013.06.021

    Article  CAS  PubMed  Google Scholar 

  12. Gecse K, Róka R, Ferrier L, Leveque M, Eutamene H, Cartier C, Ait-Belgnaoui A, Rosztóczy A, Izbéki F, Fioramonti J, Wittmann T, Bueno L (2008) Increased faecal serine protease activity in diarrhoeic IBS patients: a colonic luminal factor impairing colonic permeability and sensitivity. Gut 57(5): 591–599. https://doi.org/10.1136/gut.2007.140210

    Article  CAS  PubMed  Google Scholar 

  13. Padmaja S, Green-Johnson J (2015) Butyric acid inhibits a Toll-like receptor 2 agonist-mediated increase of Toll-like receptor 3-induced chemokine production by HT-29 intestinal epithelial cells. J Immunol 194 (1 Suppl): 196. https://doi.org/10.4049/jimmunol.194.Supp.196.11

    Article  Google Scholar 

  14. Lustgarten MS (2019) Role of the gut microbiome and short-chain fatty acids on skeletal muscle mass. Front Physiol 10: 1435. https://doi.org/10.3389/fphys.2019.01435

    Article  PubMed  PubMed Central  Google Scholar 

  15. Nobel YR, Cox LM, Kirigin FF, Bokulich NA, Yamanishi S, Teitler I, Chung J, Sohn J, Barber CM, Goldfarb DS, Raju K, Abubucker S, Zhou Y, Ruiz VE, Li H, Mitreva M, Alekseyenko AV, Weinstock GM, Sodergren E, Blaser MJ (2015) Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment. Nat Commun 6: 7486. https://doi.org/10.1038/ncomms8486

    Article  PubMed  Google Scholar 

  16. Vrieze A, Holleman F, Zoetendal EG, de Vos WM, Hoekstra JBL, Nieuwdorp M (2010) The environment within: how gut microbiota may influence metabolism and body composition. Diabetologia 53(4): 606–613. https://doi.org/10.1007/s00125-010-1662-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Lahiri S, Kim H, Garcia-Perez I, Reza MM, Martin KA, Kundu P, Cox LM, Selkrig J, Posma JM, Zhang H, Padmanabhan P, Moret C, Gulyás B, Blaser MJ, Auwerx J, Holmes E, Nicholson J, Wahli W, Pettersson S (2019) The gut microbiota influences skeletal muscle mass and function in mice. Sci Transl Med 11(502): eaan5662. https://doi.org/10.1126/scitranslmed.aan5662

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Manickam R, Oh HYP, Tan CK, Paramalingam E, Wahli W (2018) Metronidazole Causes Skeletal Muscle Atrophy and Modulates Muscle Chronometabolism. Int J Mol Sci 9(8): 2418. https://doi.org/10.3390/ijms19082418

    Article  CAS  Google Scholar 

  19. Okamoto T, Morino K, Ugi S, Nakagawa F, Lemecha M, Ida S, Ohashi N, Sato D, Fujita Y, Maegawa H (2019) Microbiome potentiates endurance exercise through intestinal acetate production. Am J Physiol Endocrinol Metab 316: E956–E966. https://doi.org/10.1152/ajpendo.00510.2018.0193-1849/19

    Article  CAS  PubMed  Google Scholar 

  20. Huang WC, Chen YH, Chuang HL, Chiu CC, Huang CC (2019) Investigation of the effects of microbiota on exercise physiological adaption, performance, and energy utilization using a Gnotobiotic animal model. Front Microbiol 10: 1906. https://doi.org/10.3389/fmicb.2019.01906

    Article  PubMed  PubMed Central  Google Scholar 

  21. Frampton J, Murphy KG, Frost G, Chambers ES (2020) Short-chain fatty acids as potential regulators of skeletal muscle metabolism and function. Nat Metab 2(9): 840–848. https://doi.org/10.1038/s42255-020-0188-7

    Article  CAS  PubMed  Google Scholar 

  22. Walsh ME, Bhattacharya A, Sataranatarajan K, Qaisar R, Sloane L, Rahman MM, Kinter M, Remmen HV (2015) The histone deacetylase inhibitor butyrate improves metabolism and reduces muscle atrophy during aging. Aging Cell 14(6): 957–970. https://doi.org/10.1111/acel.12387

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Przewłócka K, Folwarski M, Kaźmierczak-Siedlecka K, Skonieczna-Żydecka K, Kaczor JJ (2020) Gut-Muscle Axis Exists and May Affect Skeletal Muscle Adaptation to Training. Nutrients 12(5): 1451. https://doi.org/10.3390/nu12051451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Desbonnet L, Clarke G, Traplin A, O’Sullivan O, Crispie F, Moloney RD, Cotter PD, Dinan TG, Cryan JF (2015) Gut microbiota depletion from early adolescence in mice: Implications for brain and behaviour. Brain Behav Immun 48: 165–173. https://doi.org/10.1016/j.bbi.2015.04.004

    Article  CAS  PubMed  Google Scholar 

  25. De Paula Vieira A, de Passillé AM, Weary DM (2012) Effects of the early social environment on behavioral responses of dairy calves to novel events. J Dairy Sci 95(9): 5149–5155. https://doi.org/10.3168/jds.2011-5073

    Article  CAS  PubMed  Google Scholar 

  26. Karl T, Pabst R, Von Hörsten S (2003) Behavioral phenotyping of mice in pharmacological and toxicological research. Exp Toxicol Pathol 55(1): 69–83. https://doi.org/10.1078/0940-2993-00301

    Article  PubMed  Google Scholar 

  27. Weydt P, Hong SY, Kliot M, Möller T (2003) Assessing disease onset and progression in the SOD1 mouse model of ALS. NeuroReport 14(7): 1051–1054. https://doi.org/10.1097/01.wnr.0000073685.00308.89

    Article  PubMed  Google Scholar 

  28. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95(2): 351–358. https://doi.org/10.1016/0003-2697(79)90738-3

    Article  CAS  PubMed  Google Scholar 

  29. Razygraev AV, Yushina AD, Titovich IA (2018) Correction to: A Method of Measuring Glutathione Peroxidase Activity in Murine Brain: Application in Pharmacological Experiment. Bull Exp Biol Med 165(4): 589–592. https://doi.org/10.1007/s10517-018-4219-2

    Article  CAS  PubMed  Google Scholar 

  30. Yakovlev AV, Dmitrieva SA, Krasnova AN, Yakovleva OV, Sitdikova GF (2022) Levels of Protein Carbonylation and Activity of Proteases in the Brain of Newborn Rats with Prenatal Hyperhomocysteinemia. Neurochem J 16(3): 243–250. https://doi.org/10.1134/S181971242203014X

    Article  Google Scholar 

  31. Varian BJ, Goureshetti S, Poutahidis T, Lakritz JR, Levkovich T, Kwok C, Teliousis K, Ibrahim YM, Mirabal S, Erdman SE (2007) Beneficial bacteria inhibit cachexia. Oncotarget 7: 11803–11816. https://doi.org/10.18632/oncotarget.7730

    Article  Google Scholar 

  32. Mekonnen SA, Merenstein D, Fraser CM, Marco ML (2020) Molecular mechanisms of probiotic prevention of antibiotic-associated diarrhea. Curr Opin Biotechnol 61: 226–234. https://doi.org/10.1016/j.copbio.2020.01.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Pérez-Cobas AE, Gosalbes MJ, Friedrichs A, Knecht H, Artacho A, Eismann K, Otto W, Rojo D, Bargiela R, von Bergen M, Neulinger SC, Däumer C, Heinsen F-A, Latorre A, Barbas C, Seifert J, dos Santos VM, Ott SJ, Ferrer M, Moya A (2013) Gut microbiota disturbance during antibiotic therapy: a multi-omic approach. Gut 62(11): 1591–1601. https://doi.org/10.1136/gutjnl-2012-303184

    Article  CAS  PubMed  Google Scholar 

  34. Binder HJ (2010) Role of Colonic Short-chain fatty acid transport in diarrhea. Annu Rev Physiol 72: 297–313. https://doi.org/10.1146/annurev-physiol-021909-135817

    Article  CAS  PubMed  Google Scholar 

  35. Theriot CM, Koenigsknecht MJ, Carlson PE, Hatton GE, Nelson AM, Li B, Huffnagle GB, Li JZ, Young VB (2014) Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection. Nat Commun 5: 3114. https://doi.org/10.1038/ncomms4114

    Article  CAS  PubMed  Google Scholar 

  36. dos Reis SA, da Conceição LL, Rosa DD, dos Santos Dias MM, do Carmo Gouveia Peluzio M (2015) Mechanisms used by inulin-type fructans to improve the lipid profile. Nutr Hosp 31(2): 528–534. https://doi.org/10.3305/nh.2015.31.2.7706

    Article  Google Scholar 

  37. Everard A, Lazarevic V, Derrien M, Girard M, Muccioli GG, Neyrinck AM, et al. (2011) Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice. Diabetes 60: 2775–2786. https://doi.org/10.2337/db11-0227

  38. Rivière A, Selak M, Lantin D, Leroy F, De Vuyst L (2016) Bifidobacteria and Butyrate-Producing Colon Bacteria: Importance and Strategies for Their Stimulation in the Human Gut. Front Microbiol 7: 979. https://doi.org/10.3389/fmicb.2016.00979

    Article  PubMed  PubMed Central  Google Scholar 

  39. Qiu Y, Yu J, Li Y, Yang F, Yu H, Xue M, Zhang F, Jiang X, Ji X, Bao Z (2021) Depletion of gut microbiota induces skeletal muscle atrophy by FXR-FGF15/19 signalling. Ann Med 53(1): 508–522. https://doi.org/10.1080/07853890.2021.1900593

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Nedogreeva OA, Stepanichev MY, Gulyaeva NV (2020) Removal of the Olfactory Bulbs in Mice Leads to Changes in Affective Behavior. Neurosci Behav Physiol 50: 892–899. https://doi.org/10.1007/s11055-020-00982-3

    Article  Google Scholar 

  41. Hsu YJ, Chiu CC, Li YP, Huang WC, Huang YT, Huang CC, Chuang HL (2015) Effect of Intestinal Microbiota on Exercise Performance in Mice. J Strength Condit Res 29(2): 552–558. https://doi.org/10.1519/JSC.0000000000000644

    Article  Google Scholar 

  42. Chen Y-M, Wei L, Chiu Y-S, Hsu Y-J, Tsai T-Y, Wang M-F, Huang C-C (2016) Lactobacillus plantarum TWK10 supplementation improves exercise performance and increases muscle mass in mice. Nutrients 8(4): 205. https://doi.org/10.3390/nu8040205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Jäger R, Shields KA, Lowery RP, De Souza EO, Partl JM, Hollmer C, Purpura M, Wilson JM (2016) Probiotic Bacillus coagulans GBI-30, 6086 reduces exercise-induced muscle damage and increases recovery. Peer J 4: e2276. https://doi.org/10.7717/peerj.2276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Scheiman J, Luber JM, Chavkin TA, MacDonald T, Tung A, Pham LD, Wibowo MC, Wurth RC, Punthambaker S, Tierney BT, Yang Z, Hattab MW, Avila-Pacheco J, Clish CB, Lessard S, Church GM, Kostic AD (2019) Meta-omics analysis of elite athletes identifies a performance-enhancing microbe that functions via lactate metabolism. Nat Med 25(7): 1104–1109. https://doi.org/10.1038/s41591-019-0485-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Rastelli M, Cani PD, Knauf C (2019) The gut microbiome influences host endocrine function. Endocr Rev 40(5): 1271–1284. https://doi.org/10.1210/er.2018-00280

    Article  PubMed  Google Scholar 

  46. Grosicki GJ, Fielding RA, Lustgarten MS (2018) Gut microbiota contribute to age-related changes in skeletal muscle size, composition, and function: biological basis for a gut-muscle axis. Calcif Tissue Int 102(4): 433–442. https://doi.org/10.1007/s00223-017-0345-5

    Article  CAS  PubMed  Google Scholar 

  47. Guo A, Li K, Xiao Q (2020) Fibroblast growth factor 19 alleviates palmitic acid-induced mitochondrial dysfunction and oxidative stress via the AMPK/PGC-1α pathway in skeletal muscle. Biochem Biophys Res Commun 526(4): 1069–1076. https://doi.org/10.1016/j.bbrc.2020.04.002

    Article  CAS  PubMed  Google Scholar 

  48. Brown AJ, Goldsworthy SM, Barnes AA, Eilert MM, Tcheang L, Daniels D, Muir AI, Wigglesworth MJ, Kinghorn I, Fraser NJ, Pike NB, Strum JC, Steplewski KM, Murdock PR, Holder JC, Marshall FH, Szekeres PG, Wilson S, Ignar DM, Foord SM, Wise A, Dowell SJ (2003) The orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem 278(13): 11312–11319. https://doi.org/10.1074/jbc.M211609200

    Article  CAS  PubMed  Google Scholar 

  49. Nilsson NE, Kotarsky K, Owman C, Olde B (2003) Identification of a free fatty acid receptor, FFA2R, expressed on leukocytes and activated by short-chain fatty acids. Biochem Biophys Res Commun 303(4): 1047–1052. https://doi.org/10.1016/s0006-291x(03)00488-1

    Article  CAS  PubMed  Google Scholar 

  50. Ticinesi A, Lauretani F, Milani C, Nouvenne A, Tana C, Del Rio D, Maggio M, Ventura M, Meschi T (2017) Aging gut microbiota at the cross-road between nutrition, physical frailty, and sarcopenia: Is there a gut–muscle axis? Nutrients 9(12): 1303. https://doi.org/10.3390/nu9121303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Gao Z, Yin J, Zhang J, Ward RE, Martin RJ, Lefevre M, Cefalu WT, Ye J (2009) Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes 58(7): 1509–1517. https://doi.org/10.2337/db08-1637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Kalghatgi S, Spina CS, Costello JC, Liesa M, Morones-Ramirez JR, Slomovic S, Molina A, Shirihai OS, Collins JJ (2013) Bactericidal Antibiotics Induce Mitochondrial Dysfunction and Oxidative Damage in Mammalian Cells. Sci Transl Med 5(192): 192ra85. https://doi.org/10.1126/scitranslmed.3006055

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Chen LH, Snyder DL (1992) Effects of age, dietary restriction and germ-free environment on glutathione-related enzymes in Lobund-Wistar rats. Arch Gerontol Geriatr 14(1): 17–26. https://doi.org/10.1016/0167-4943(92)90003-m

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by the Russian Science Foundation and the Cabinet of Ministers of the Republic of Tatarstan (Project no. 22-25-20045).

Author information

Authors and Affiliations

  1. Kazan Federal University, Kazan, Russia

    O. V. Yakovleva, A. I. Mullakaeva, A. F. Salikhzyanova, D. M. Sorokina & G. F. Sitdikova

Authors
  1. O. V. Yakovleva
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. I. Mullakaeva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. F. Salikhzyanova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. M. Sorokina
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. F. Sitdikova
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Idea of work and planning the experiment—S.G.F., S.D.M., Ya.O.V., data collection—M.A.I., S.A.F., data processing—Ya.O.V., M.A.I., S.A.F., article writing and editing—Ya.O.V., S.G.F., M.A.I., S.D.M., S.A.F.

Corresponding author

Correspondence to O. V. Yakovleva.

Ethics declarations

COMPLIANCE WITH ETHICAL STANDARDS

All experimental procedures complied with ethical standards approved by legal acts of the Russian Federation, were performed in accordance with the principles of the Helsinki Declaration on the Humane Treatment of Animals, and were approved by the Local Ethics Committee of Kazan Federal University (protocol no. 33 of November 25, 2021).

CONFLICT OF INTEREST

The authors declare that they have no conflicts of interest.

Additional information

Translated by A. Dyomina

Russian Text © The Author(s), 2023, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2023, Vol. 109, No. 6, pp. 723–736https://doi.org/10.31857/S0869813923060067.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yakovleva, O.V., Mullakaeva, A.I., Salikhzyanova, A.F. et al. The Effect of the Microbiota Metabolite—Butyric Acid on Motor Coordination, Muscle Strength and the Level of Oxidative Stress in Skeletal Muscles in Mice with Dysbiosis. J Evol Biochem Phys 59, 930–940 (2023). https://doi.org/10.1134/S0022093023030249

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0022093023030249

Keywords:

Search

Navigation