The main factors that improve gut microbiota composition




probiotics, prebiotics, synbiotics, gastrointestinal microbiome, metabolomics, coronary artery disease


The aim is to observe and compare the main factors that can improve gut microbiota composition.

Materials and methods. The literature study research was performed in PubMed and Google Scholar electronic databases. We assessed more than 300 studies, data from 65 of which were included in this review. They are presented in three tables: nonpharmacological influence on gut microbiota composition, drugs impact on gut microbiota, and medicines prescribed for gut microbiota correction.

Results. On the one hand, non-pharmacological methods of gut microbiota improvement are the safest and the most traditional: healthy diet and physical activity, good sleep, avoiding stress and bad habits, but they are the most difficult for patients’ fulfillment and doctors’ observation. All listed are the components of a healthy way of life and should be followed by everybody. The most prescribed drugs have a significant influence on gut microbiota composition, so physicians should consider their effects in prescriptions. They are antibiotics, steroids and non-steroids, proton pump inhibitors, laxatives, antidepressants, etc.

On the other hand, despite the diversity of available medicines (prebiotics, probiotics, paraprobiotics, postbiotics, synbiotics, and antibiotics) that can be used for gut microbiota improvement, all of them are under investigation and need further evaluation. The trendiest medicines for today are paraprobiotics and postbiotics. Paraprobiotics are represented by heat / ultraviolet / sonication Lactobacillus spp., Bifidobacterium spp., and Saccharomyces strains. Postbiotics are performed by short-chain fatty acids, secreted biosurfactants, secreted proteins, organic acids, amino acids, bacteriocins, vitamins, and peptides. Most of the data on their pharmacodynamics is based on animal studies or experimental research, so they need further investigations. Fecal gut microbiota transplantation is also an up-to-date method for multiple disease correction but is approved only for the treatment of recurrent and refractory infections caused by Clostridium difficile.

Conclusions. Gut microbiota composition improvement methods are an up-to-date topic for practical medicine because gut microbiota changes are closely linked with host health status. Gut microbiota violations lead to metabolic, cardiovascular, neurological, inflammatory disorders, etc. Nowadays the healthy way of life is the best gut microbiota composition improvement method, but prebiotics, probiotics, paraprobiotics, postbiotics, synbiotics, antibiotics supplementation, and fecal microbiota transplantation also take place and have their indisputable advantages in special cases. Unfortunately, most pharmacological methods of gut microbiota modulation have a weak evidence base. Therefore, this question needs further research in appropriate patient groups with long-term monitoring.

Author Biographies

I. O. Melnychuk, Bogomolets National Medical University, Kyiv, Ukraine

MD, PhD, Associate Professor of the Department of Internal Medicine No. 4

M. L. Sharaieva, Bogomolets National Medical University, Kyiv, Ukraine

MD, PhD, Associate Professor of Internal Medicine Department No. 4

Amrita Gargi, Bogomolets National Medical University, Kyiv, Ukraine

5th course student

V. H. Lyzogub , Bogomolets National Medical University, Kyiv, Ukraine

MD, PhD, DSc, Professor, Head of Internal Medicine Department No. 4


Bordenstein SR, Theis KR. Host Biology in Light of the Microbiome: Ten Principles of Holobionts and Hologenomes. PLoS Biol. 2015;13(8):e1002226. doi:

Inda MC, Joshi S, Wang T, Bolaender A, Gandu S, Koren Iii J, et al. The epichaperome is a mediator of toxic hippocampal stress and leads to protein connectivity-based dysfunction. Nat Commun. 2020;11(1):319. doi:

Forkosh E, Ilan Y. The heart-gut axis: new target for atherosclerosis and congestive heart failure therapy. Open Heart. 2019;6(1):e000993. doi:

Hou K, Wu ZX, Chen XY, Wang JQ, Zhang D, Xiao C, et al. Microbiota in health and diseases. Signal Transduct Target Ther. 2022;7(1):135. doi:

Gebrayel P, Nicco C, Al Khodor S, Bilinski J, Caselli E, Comelli EM, et al. Microbiota medicine: towards clinical revolution. J Transl Med. 2022;20(1):111. doi:

Mamic P, Snyder M, Tang WH. Gut Microbiome-Based Management of Patients With Heart Failure: JACC Review Topic of the Week. J Am Coll Cardiol. 2023;81(17):1729-39. doi:

Vich Vila A, Collij V, Sanna S, Sinha T, Imhann F, Bourgonje AR, et al. Impact of commonly used drugs on the composition and metabolic function of the gut microbiota. Nat Commun. 2020;11(1):362. doi:

Trøseid M, Andersen GØ, Broch K, Hov JR. The gut microbiome in coronary artery disease and heart failure: Current knowledge and future directions. EBioMedicine. 2020;52:102649. doi:

Liu H, Chen X, Hu X, Niu H, Tian R, Wang H, et al. Alterations in the gut microbiome and metabolism with coronary artery disease severity. Microbiome. 2019;7(1):68. doi:

Takiishi T, Fenero CIM, Câmara NOS. Intestinal barrier and gut microbiota: Shaping our immune responses throughout life. Tissue Barriers. 2017;5(4):e1373208. doi:

Lyzohub VH, Kramarova VN, Melnychuk IO. [Role of intestinal microbiota changes in cardiovascular diseases pathogenesis]. Zaporozhye medical journal. 2019;(5):672-8. Ukrainian. doi:

Adak A, Khan MR. An insight into gut microbiota and its functionalities. Cell Mol Life Sci. 2019;76(3):473-93. doi:

Fong W, Li Q, Yu J. Gut microbiota modulation: a novel strategy for prevention and treatment of colorectal cancer. Oncogene. 2020;39(26):4925-43. doi:

Bibbò S, Ianiro G, Giorgio V, Scaldaferri F, Masucci L, Gasbarrini A, et al. The role of diet on gut microbiota composition. Eur Rev Med Pharmacol Sci. 2016;20(22):4742-9.

Campaniello D, Corbo MR, Sinigaglia M, Speranza B, Racioppo A, Altieri C, et al. How Diet and Physical Activity Modulate Gut Microbiota: Evidence, and Perspectives. Nutrients. 2022;14(12):2456. doi:

Losno EA, Sieferle K, Perez-Cueto FJA, Ritz C. Vegan Diet and the Gut Microbiota Composition in Healthy Adults. Nutrients. 2021;13(7):2402. doi:

Kahleova H, Rembert E, Alwarith J, Yonas WN, Tura A, Holubkov R, et al. Effects of a Low-Fat Vegan Diet on Gut Microbiota in Overweight Individuals and Relationships with Body Weight, Body Composition, and Insulin Sensitivity. A Randomized Clinical Trial. Nutrients. 2020;12(10):2917. doi:

Argyridou S, Davies MJ, Biddle GJ, Bernieh D, Suzuki T, Dawkins NP, et al. Evaluation of an 8-Week Vegan Diet on Plasma Trimethylamine-N-Oxide and Postchallenge Glucose in Adults with Dysglycemia or Obesity. J Nutr. 2021;151(7):1844-53. doi:

Codella R, Luzi L, Terruzzi I. Exercise has the guts: How physical activity may positively modulate gut microbiota in chronic and immune-based diseases. Dig Liver Dis. 2018;50(4):331-41. doi:

Argyridou S, Bernieh D, Henson J, Edwardson CL, Davies MJ, Khunti K, et al. Associations between physical activity and trimethylamine N-oxide in those at risk of type 2 diabetes. BMJ Open Diabetes Res Care. 2020;8(2):e001359. doi:

Neroni B, Evangelisti M, Radocchia G, Di Nardo G, Pantanella F, Villa MP, et al. Relationship between sleep disorders and gut dysbiosis: what affects what? Sleep Med. 2021;87:1-7. doi:

Molina-Torres G, Rodriguez-Arrastia M, Roman P, Sanchez-Labraca N, Cardona D. Stress and the gut microbiota-brain axis. Behav Pharmacol. 2019;30(2 and 3-Spec Issue):187-200. doi:

Fan J, Zhou Y, Meng R, Tang J, Zhu J, Aldrich MC, et al. Cross-talks between gut microbiota and tobacco smoking: a two-sample Mendelian randomization study. BMC Med. 2023;21(1):163. doi:

Antinozzi M, Giffi M, Sini N, Gallè F, Valeriani F, De Vito C, et al. Cigarette Smoking and Human Gut Microbiota in Healthy Adults: A Systematic Review. Biomedicines. 2022;10(2):510. doi:

Engen PA, Green SJ, Voigt RM, Forsyth CB, Keshavarzian A. The Gastrointestinal Microbiome: Alcohol Effects on the Composition of Intestinal Microbiota. Alcohol Res. 2015;37(2):223-36.

Ianiro G, Tilg H, Gasbarrini A. Antibiotics as deep modulators of gut microbiota: between good and evil. Gut. 2016;65(11):1906-15. doi:

Ramirez J, Guarner F, Bustos Fernandez L, Maruy A, Sdepanian VL, Cohen H. Antibiotics as Major Disruptors of Gut Microbiota. Front Cell Infect Microbiol. 2020;10:572912. doi:

Maseda D, Ricciotti E. NSAID-Gut Microbiota Interactions. Front Pharmacol. 2020;11:1153. doi:

Gibson GR, Hutkins R, Sanders ME, Prescott SL, Reimer RA, Salminen SJ, et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. 2017;14(8):491-502. doi:

Wang X, Yue H, Zhang H, Wan L, Ji S, Geng C. Preventive Effects of Long-Term Intake of Plant Oils With Different Linoleic Acid/Alpha-Linolenic Acid Ratios on Acute Colitis Mouse Model. Front Nutr. 2022;9:788775. doi:

Xie J, Li LF, Dai TY, Qi X, Wang Y, Zheng TZ, et al. Short-Chain Fatty Acids Produced by Ruminococcaceae Mediate α-Linolenic Acid Promote Intestinal Stem Cells Proliferation. Mol Nutr Food Res. 2022;66(1):e2100408. doi:

Mercola J, D'Adamo CR. Linoleic Acid: A Narrative Review of the Effects of Increased Intake in the Standard American Diet and Associations with Chronic Disease. Nutrients. 2023;15(14):3129. doi:

Djuricic I, Calder PC. Polyunsaturated fatty acids and metabolic health: novel insights. Curr Opin Clin Nutr Metab Care. 2022;25(6):436-42. doi:

Fu Y, Wang Y, Gao H, Li D, Jiang R, Ge L, et al. Associations among Dietary Omega-3 Polyunsaturated Fatty Acids, the Gut Microbiota, and Intestinal Immunity. Mediators Inflamm. 2021;2021:8879227. doi:

Molendi-Coste O, Legry V, Leclercq IA. Why and How Meet n-3 PUFA Dietary Recommendations? Gastroenterol Res Pract. 2011;2011:364040. doi:

Hughes RL, Alvarado DA, Swanson KS, Holscher HD. The Prebiotic Potential of Inulin-Type Fructans: A Systematic Review. Adv Nutr. 2022;13(2):492-529. doi:

Okburan G, Kızıler S. Human milk oligosaccharides as prebiotics. Pediatr Neonatol. 2023;64(3):231-8. doi:

Yang Z, Huang T, Li P, Ai J, Liu J, Bai W, et al. Dietary Fiber Modulates the Fermentation Patterns of Cyanidin-3-O-Glucoside in a Fiber-Type Dependent Manner. Foods. 2021;10(6):1386. doi:

Schaafsma A, Mallee L, van den Belt M, Floris E, Kortman G, Veldman J, et al. The Effect of A Whey-Protein and Galacto-Oligosaccharides Based Product on Parameters of Sleep Quality, Stress, and Gut Microbiota in Apparently Healthy Adults with Moderate Sleep Disturbances: A Randomized Controlled Cross-Over Study. Nutrients. 2021;13(7):2204. doi:

Villageliú D, Lyte M. Dopamine production in Enterococcus faecium: A microbial endocrinology-based mechanism for the selection of probiotics based on neurochemical-producing potential. PLoS One. 2018;13(11):e0207038. doi:

Suh MG, Bae GY, Jo K, Kim JM, Hong KB, Suh HJ. Photoprotective Effect of Dietary Galacto-Oligosaccharide (GOS) in Hairless Mice via Regulation of the MAPK Signaling Pathway. Molecules. 2020;25(7):1679. doi:

Filosa S, Di Meo F, Crispi S. Polyphenols-gut microbiota interplay and brain neuromodulation. Neural Regen Res. 2018;13(12):2055-9. doi:

Luo C, Wei X, Song J, Xu X, Huang H, Fan S, et al. Interactions between Gut Microbiota and Polyphenols: New Insights into the Treatment of Fatigue. Molecules. 2022;27(21):7377. doi:

Davinelli S, Scapagnini G. Interactions between dietary polyphenols and aging gut microbiota: A review. Biofactors. 2022;48(2):274-84. doi:

Duda-Chodak A, Tarko T. Possible Side Effects of Polyphenols and Their Interactions with Medicines. Molecules. 2023;28(6):2536. doi:

Cronin P, Joyce SA, O'Toole PW, O'Connor EM. Dietary Fibre Modulates the Gut Microbiota. Nutrients. 2021;13(5):1655. doi:

Zapico A, Arboleya S, Ruiz-Saavedra S, Gómez-Martín M, Salazar N, Nogacka AM, et al. Dietary xenobiotics, (poly)phenols and fibers: Exploring associations with gut microbiota in socially vulnerable individuals. Front Nutr. 2022;9:1000829. doi:

Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11(8):506-14. doi:

Azad MA, Sarker M, Li T, Yin J. Probiotic Species in the Modulation of Gut Microbiota: An Overview. Biomed Res Int. 2018;2018:9478630. doi:

Zawistowska-Rojek A, Tyski S. Are Probiotic Really Safe for Humans? Pol J Microbiol. 2018;67(3):251-8. doi:

Gawałko M, Agbaedeng TA, Saljic A, Müller DN, Wilck N, Schnabel R, et al. Gut microbiota, dysbiosis and atrial fibrillation. Arrhythmogenic mechanisms and potential clinical implications. Cardiovasc Res. 2022;118(11):2415-27. doi:

Kaźmierczak-Siedlecka K, Ruszkowski J, Fic M, Folwarski M, Makarewicz W. Saccharomyces boulardii CNCM I-745: A Non-bacterial Microorganism Used as Probiotic Agent in Supporting Treatment of Selected Diseases. Curr Microbiol. 2020;77(9):1987-96. doi:

Ma X, Tian M, Yu X, Liu M, Li B, Ren D, et al. Characterization and Preliminary Safety Evaluation of Akkermansia muciniphila PROBIO. Foods. 2024;13(3):442. doi:

Konstanti P, Ligthart K, Fryganas C, Constantinos P, Smidt H, de Vos WM, et al. Physiology of γ-aminobutyric acid production by Akkermansia muciniphila. Appl Environ Microbiol. 2024;90(1):e0112123. doi:

Yaghoubfar R, Zare BanadKoki E, Ashrafian F, Shahryari A, Kariman A, Davari M, et al. The impact of Akkermansia muciniphila and its extracellular vesicles in the regulation of serotonergic gene expression in a small intestine of mice. Anaerobe. 2023;83:102786. doi:

Zhao X, Zhao J, Li D, Yang H, Chen C, Qin M, et al. Akkermansia muciniphila: A potential target and pending issues for oncotherapy. Pharmacol Res. 2023;196:106916. doi:

Nataraj BH, Ali SA, Behare PV, Yadav H. Postbiotics-parabiotics: the new horizons in microbial biotherapy and functional foods. Microb Cell Fact. 2020;19(1):168. doi:

Li HY, Zhou DD, Gan RY, Huang SY, Zhao CN, Shang A, et al. Effects and Mechanisms of Probiotics, Prebiotics, Synbiotics, and Postbiotics on Metabolic Diseases Targeting Gut Microbiota: A Narrative Review. Nutrients. 2021;13(9):3211. doi:

Cuevas-González PF, Liceaga AM, Aguilar-Toalá JE. Postbiotics and paraprobiotics: From concepts to applications. Food Res Int. 2020;136:109502. doi:

Siciliano RA, Reale A, Mazzeo MF, Morandi S, Silvetti T, Brasca M. Paraprobiotics: A New Perspective for Functional Foods and Nutraceuticals. Nutrients. 2021;13(4):1225. doi:

Scott E, De Paepe K, Van de Wiele T. Postbiotics and Their Health Modulatory Biomolecules. Biomolecules. 2022;12(11):1640. doi:

Panebianco C, Villani A, Pisati F, Orsenigo F, Ulaszewska M, Latiano TP, et al. Butyrate, a postbiotic of intestinal bacteria, affects pancreatic cancer and gemcitabine response in in vitro and in vivo models. Biomed Pharmacother. 2022;151:113163. doi:

Maguire M, Maguire G. Gut dysbiosis, leaky gut, and intestinal epithelial proliferation in neurological disorders: towards the development of a new therapeutic using amino acids, prebiotics, probiotics, and postbiotics. Rev Neurosci. 2019;30(2):179-201. doi:

Wang JW, Kuo CH, Kuo FC, Wang YK, Hsu WH, Yu FJ, et al. Fecal microbiota transplantation: Review and update. J Formos Med Assoc. 2019;118 Suppl 1:S23-1. doi:




How to Cite

Melnychuk, I. O., Sharaieva, M. L., Gargi, A., & Lyzogub , V. H. (2024). The main factors that improve gut microbiota composition. Modern Medical Technology, 16(2), 132–143.



Reviews of literature