Current Understating of Gut Microbiome Alterations and Therapeutic Approaches for Improving Human Health

  • Rithi AT Department of Pharmacology, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Chennai-603103, Tamil Nadu, India https://orcid.org/0009-0006-3297-2359
  • Abhijit Mitra Medical Biotechnology lab, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Chennai-603103, Tamil Nadu, India https://orcid.org/0000-0001-9549-2930
  • Antara Banerjee Medical Biotechnology lab, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Chennai-603103, Tamil Nadu, India https://orcid.org/0000-0002-5519-6878
  • Divya Ilanchoorian Department of Community Medicine, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Chennai-603103, Tamil Nadu, India
  • Arun Kumar Radhakrishnan Department of Pharmacology, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Chennai-603103, Tamil Nadu, India
Keywords: Anti-microbial therapies, Clostridioides difficile infection, fecal microbiota transplantation, gut microbiome, prebiotics, probiotics

Abstract

Millions of microorganisms, including bacteria, fungi, and viruses compose the human gut microbiome. There is variation in the composition of species from the moment of birth throughout the whole human lifecycle. Gut microbiome play a central role in maintaining body equilibrium, influencing a range of physiological processes including metabolism, the maintenance of barriers, inflammation, and hematopoiesis, both within and outside the intestines. An imbalanced microbial environment within the gastrointestinal tract is at the core of numerous diseases, such as inflammatory bowel disorder, obesity, diabetes, and Clostridioides difficile infection, and plays a pivotal role in their development. In this review, we discuss the therapeutic approaches of gut microbiome-related therapies including fecal microbiota transplantation, anti-microbial therapies, prebiotics, probiotics and Dietary interventions to repair the altered gut microbiome composition. The pursuit of new therapies and their subsequent improvement is propelled by an ongoing requirement for evaluation, experimentation, laboratory procedures, and the ethical and technological limitations associated with clinical translation.

References

Afzaal, M., Saeed, F., Shah, Y. A., Hussain, M., Rabail, R., Socol, C. T., Hassoun, A., Pateiro, M., Lorenzo, J. M., Rusu, A. V., & Aadil, R. M. (2022). Human gut microbiota in health and disease: Unveiling the relationship. Frontiers in Microbiology, 13, 999001. https://doi.org/10.3389/fmicb.2022.999001

Banerjee, A., Somasundaram, I., Das, D., Jain Manoj, S., Banu, H., Mitta Suresh, P., Paul, S., Bisgin, A., Zhang, H., Sun, X.-F., Duttaroy, A. K., & Pathak, S. (2023). Functional Foods: A Promising Strategy for Restoring Gut Microbiota Diversity Impacted by SARS-CoV-2 Variants. Nutrients, 15(11), 2631. https://doi.org/10.3390/nu15112631

Bear, T.L.K., Dalziel, J.E., Coad, J., Roy, N.C., Butts, C.A. and Gopal, P.K. (2020). The Role of the Gut Microbiota in Dietary Interventions for Depression and Anxiety. Advances in Nutrition, 11(4), 890–907. https://doi.org/10.1093/advances/nmaa016

Bhalodi, A. A., van Engelen, T. S. R., Virk, H. S., & Wiersinga, W. J. (2019). Impact of antimicrobial therapy on the gut microbiome. Journal of Antimicrobial Chemotherapy, 74(Supplement_1), i6–i15. https://doi.org/10.1093/jac/dky530

Brandt, L. J. (2013). American Journal of Gastroenterology Lecture: Intestinal Microbiota and the Role of Fecal Microbiota Transplant (FMT) in Treatment of C. difficile Infection. American Journal of Gastroenterology, 108(2), 177–185. https://doi.org/10.1038/ajg.2012.450

Bull, M. J., & Plummer, N. T. (2014). Part 1: The Human Gut Microbiome in Health and Disease. Integrative Medicine (Encinitas, Calif.), 13(6), 17–22. http://www.ncbi.nlm.nih.gov/pubmed/26770121

Cho, I., Yamanishi, S., Cox, L., Methé, B. A., Zavadil, J., Li, K., Gao, Z., Mahana, D., Raju, K., Teitler, I., Li, H., Alekseyenko, A. V., & Blaser, M. J. (2012). Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature, 488(7413), 621–626. https://doi.org/10.1038/nature11400

Choo, J. M., Kanno, T., Zain, N. M. M., Leong, L. E. X., Abell, G. C. J., Keeble, J. E., Bruce, K. D., Mason, A. J., & Rogers, G. B. (2017). Divergent Relationships between Fecal Microbiota and Metabolome following Distinct Antibiotic-Induced Disruptions. mSphere, 2(1), e00005-17. https://doi.org/10.1128/mSphere.00005-17

Colman, R. J., & Rubin, D. T. (2014). Fecal microbiota transplantation as therapy for inflammatory bowel disease: A systematic review and meta-analysis. Journal of Crohn’s and Colitis, 8(12), 1569–1581. https://doi.org/10.1016/j.crohns.2014.08.006

Colombel, J. F. (2014). IBD—genes, bacteria and new therapeutic strategies. Nature Reviews Gastroenterology & Hepatology, 11(11), 652–654. https://doi.org/10.1038/nrgastro.2014.170

Davani-Davari, D., Negahdaripour, M., Karimzadeh, I., Seifan, M., Mohkam, M., Masoumi, S., Berenjian, A., & Ghasemi, Y. (2019). Prebiotics: Definition, Types, Sources, Mechanisms, and Clinical Applications. Foods, 8(3), 92.

https://doi.org/10.3390/foods8030092

De Filippis, F., Vitaglione, P., Cuomo, R., Berni Canani, R. and Ercolini, D. (2018). Dietary Interventions to Modulate the Gut Microbiome—How Far Away Are We from Precision Medicine. Inflammatory Bowel Diseases, 24(10), 2142–2154. https://doi.org/10.1093/ibd/izy080.

Depommier, C., Everard, A., Druart, C., Plovier, H., Van Hul, M., Vieira-Silva, S., Falony, G., Raes, J., Maiter, D., Delzenne, N. M., de Barsy, M., Loumaye, A., Hermans, M. P., Thissen, J.P., de Vos, W. M., & Cani, P. D. (2019). Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nature Medicine, 25(7), 1096–1103. https://doi.org/10.1038/s41591-019-0495-2

Dubberke, E. R., Mullane, K. M., Gerding, D. N., Lee, C. H., Louie, T. J., Guthertz, H., & Jones, C. (2016). Clearance of Vancomycin-Resistant Enterococcus Concomitant With Administration of a Microbiota-Based Drug Targeted at Recurrent Clostridium difficile Infection. Open Forum Infectious Diseases, 3(3). https://doi.org/10.1093/ofid/ofw133

Farias, D. de P., de Araújo, F.F., Neri-Numa, I.A. and Pastore, G.M. (2019). Prebiotics: Trends in food, health and technological applications. Trends in Food Science & Technology, 93, 23–35. https://doi.org/10.1016/j.tifs.2019.09.004.

Fernández, J., Ledesma, E., Monte, J., Millán, E., Costa, P., de la Fuente, V. G., García, M. T. F., Martínez-Camblor, P., Villar, C. J., & Lombó, F. (2019). Traditional Processed Meat Products Re-designed Towards Inulin-rich Functional Foods Reduce Polyps in Two Colorectal Cancer Animal Models. Scientific Reports, 9(1), 14783. https://doi.org/10.1038/s41598-019-51437-w

Fidelis, M., Santos, J. S., Escher, G. B., Rocha, R. S., Cruz, A. G., Cruz, T. M., Marques, M. B., Nunes, J. B., do Carmo, M. A. V., de Almeida, L. A., Kaneshima, T., Azevedo, L., & Granato, D. (2021). Polyphenols of jabuticaba [Myrciaria jaboticaba (Vell.) O.Berg] seeds incorporated in a yogurt model exert antioxidant activity and modulate gut microbiota of 1,2-dimethylhydrazine-induced colon cancer in rats. Food Chemistry, 334, 127565. https://doi.org/10.1016/j.foodchem.2020.127565

Gibson, G. R., & Roberfroid, M. B. (1995). Dietary Modulation of the Human Colonic Microbiota: Introducing the Concept of Prebiotics. The Journal of Nutrition, 125(6), 1401–1412. https://doi.org/10.1093/jn/125.6.1401

Gibson, P.R., & Shepherd, S.J. (2005). Personal view: food for thought - western lifestyle and susceptibility to Crohn’s disease. The FODMAP hypothesis. Alimentary Pharmacology and Therapeutics, [online] 21(12), pp.1399–1409. https://doi.org/10.1111/j.1365-2036.2005.02506.x.

Giedraitienė, A., Vitkauskienė, A., Naginienė, R., & Pavilonis, A. (2011). Antibiotic Resistance Mechanisms of Clinically Important Bacteria. Medicina, 47(3), 19. https://doi.org/10.3390/medicina47030019

Gulliver, E. L., Young, R. B., Chonwerawong, M., D’Adamo, G. L., Thomason, T., Widdop, J. T., Rutten, E. L., Rossetto Marcelino, V., Bryant, R. V., Costello, S. P., O’Brien, C. L., Hold, G. L., Giles, E. M., & Forster, S. C. (2022). Review article: the future of microbiome‐based therapeutics. Alimentary Pharmacology & Therapeutics, 56(2), 192–208. https://doi.org/10.1111/apt.17049

Gupta, A., & Khanna, S. (2017). Fecal Microbiota Transplantation. JAMA, 318(1), 102. https://doi.org/10.1001/jama.2017.6466

Gupta, A., Saha, S., & Khanna, S. (2020). Therapies to modulate gut microbiota: Past, present and future. World Journal of Gastroenterology, 26(8), 777–788. https://doi.org/10.3748/wjg.v26.i8.777

Hemarajata, P., & Versalovic, J. (2013). Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation. Therapeutic Advances in Gastroenterology, 6(1), 39–51. https://doi.org/10.1177/1756283X12459294

Hernando-Amado, S., Coque, T. M., Baquero, F., & Martínez, J. L. (2019). Defining and combating antibiotic resistance from One Health and Global Health perspectives. Nature Microbiology, 4(9), 1432–1442. https://doi.org/10.1038/s41564-019-0503-9

Iqbal, Z., Ahmed, S., Tabassum, N., Bhattacharya, R., & Bose, D. (2021). Role of probiotics in prevention and treatment of enteric infections: a comprehensive review. 3 Biotech, 11(5), 242. https://doi.org/10.1007/s13205-021-02796-7

Kassam, Z., Lee, C. H., Yuan, Y., & Hunt, R. H. (2013). Fecal Microbiota Transplantation for Clostridium difficile Infection: Systematic Review and Meta-Analysis. American Journal of Gastroenterology, 108(4), 500–508. https://doi.org/10.1038/ajg.2013.59

Kassinen, A., Krogius-Kurikka, L., Mäkivuokko, H., Rinttilä, T., Paulin, L., Corander, J., Malinen, E., Apajalahti, J., & Palva, A. (2007). The Fecal Microbiota of Irritable Bowel Syndrome Patients Differs Significantly From That of Healthy Subjects. Gastroenterology, 133(1), 24–33. https://doi.org/10.1053/j.gastro.2007.04.005

Khanna, S. (2018). Microbiota Replacement Therapies: Innovation in Gastrointestinal Care. Clinical Pharmacology & Therapeutics, 103(1), 102–111. https://doi.org/10.1002/cpt.923

Klein, E. Y., Van Boeckel, T. P., Martinez, E. M., Pant, S., Gandra, S., Levin, S. A., Goossens, H., & Laxminarayan, R. (2018). Global increase and geographic convergence in antibiotic consumption between 2000 and 2015. Proceedings of the National Academy of Sciences, 115(15). https://doi.org/10.1073/pnas.1717295115

Kosnicki, K. L., Penprase, J. C., Cintora, P., Torres, P. J., Harris, G. L., Brasser, S. M., & Kelley, S. T. (2019). Effects of moderate, voluntary ethanol consumption on the rat and human gut microbiome. Addiction Biology, 24(4), 617–630. https://doi.org/10.1111/adb.12626

Lamichhane, S., Sen, P., Dickens, A. M., Orešič, M., & Bertram, H. C. (2018). Gut metabolome meets microbiome: A methodological perspective to understand the relationship between host and microbe. Methods, 149, 3–12. https://doi.org/10.1016/j.ymeth.2018.04.029

Lee, D., Baldassano, R.N., Otley, A.R., Albenberg, L., Griffiths, A.M., Compher, C., Chen, E.Z., Li, H., Gilroy, E., Nessel, L., Grant, A., Chehoud, C., Bushman, F.D., Wu, G.D. and Lewis, J.D. (2015). Comparative Effectiveness of Nutritional and Biological Therapy in North American Children with Active Crohnʼs Disease. Inflammatory Bowel Diseases, 21(8), 1786–1793. https://doi.org/10.1097/mib.0000000000000426.

Lindefeldt, M., Eng, A., Darban, H., Bjerkner, A., Zetterström, C. K., Allander, T., Andersson, B., Borenstein, E., Dahlin, M., & Prast-Nielsen, S. (2019). The ketogenic diet influences taxonomic and functional composition of the gut microbiota in children with severe epilepsy. Npj Biofilms and Microbiomes, 5(1), 5. https://doi.org/10.1038/s41522-018-0073-2

Looft, T., Johnson, T. A., Allen, H. K., Bayles, D. O., Alt, D. P., Stedtfeld, R. D., Sul, W. J., Stedtfeld, T. M., Chai, B., Cole, J. R., Hashsham, S. A., Tiedje, J. M., & Stanton, T. B. (2012). In-feed antibiotic effects on the swine intestinal microbiome. Proceedings of the National Academy of Sciences, 109(5), 1691–1696. https://doi.org/10.1073/pnas.1120238109

Markowiak, P., & Śliżewska, K. (2017). Effects of Probiotics, Prebiotics, and Synbiotics on Human Health. Nutrients, 9(9), 1021. https://doi.org/10.3390/nu9091021

Martinez, S., Campa, A., Narasimhan, G., Portuando, D., Seminario, L., Jasmin, J., & Baum, M. (2019). Pilot Study on the Effect of Cocaine Use on the Intestinal Microbiome and Metabolome and Inflammation in HIV-Infected Adults in the Miami Adult Studies in HIV (MASH) Cohort (P13-027-19). Current Developments in Nutrition, 3, nzz036.P13-027-19. https://doi.org/10.1093/cdn/nzz036.P13-027-19

Oniszczuk, A., Oniszczuk, T., Gancarz, M., & Szymańska, J. (2021). Role of Gut Microbiota, Probiotics and Prebiotics in the Cardiovascular Diseases. Molecules, 26(4), 1172. https://doi.org/10.3390/molecules26041172

Palleja, A., Mikkelsen, K. H., Forslund, S. K., Kashani, A., Allin, K. H., Nielsen, T., Hansen, T. H., Liang, S., Feng, Q., Zhang, C., Pyl, P. T., Coelho, L. P., Yang, H., Wang, J., Typas, A., Nielsen, M. F., Nielsen, H. B., Bork, P., Wang, J., Vilsbøll, T., Hansen, T., Knop, F. K., Arumugam, M. & Pedersen, O. (2018). Recovery of gut microbiota of healthy adults following antibiotic exposure. Nature Microbiology, 3(11), 1255–1265. https://doi.org/10.1038/s41564-018-0257-9

Panda, S., El khader, I., Casellas, F., López Vivancos, J., García Cors, M., Santiago, A., Cuenca, S., Guarner, F., & Manichanh, C. (2014). Short-Term Effect of Antibiotics on Human Gut Microbiota. PLoS ONE, 9(4), e95476. https://doi.org/10.1371/journal.pone.0095476

Pinn, D. M., Aroniadis, O. C., & Brandt, L. J. (2014). Is Fecal Microbiota Transplantation the Answer for Irritable Bowel Syndrome? A Single-Center Experience. American Journal of Gastroenterology, 109(11), 1831–1832. https://doi.org/10.1038/ajg.2014.295

Preidis, G.A., Saulnier, D.M., Blutt, S.E., Mistretta, T.-A., Riehle, K.P., Major, A.M., Venable, S.F., Finegold, M.J., Petrosino, J.F., Conner, M.E. and Versalovic, J. (2012). Probiotics stimulate enterocyte migration and microbial diversity in the neonatal mouse intestine. FASEB journal: official publication of the Federation of American Societies for Experimental Biology, 26(5), 1960–1969. https://doi.org/10.1096/fj.10-177980.

Qazi, T., Amaratunga, T., Barnes, E. L., Fischer, M., Kassam, Z., & Allegretti, J. R. (2017). The risk of inflammatory bowel disease flares after fecal microbiota transplantation: Systematic review and meta-analysis. Gut Microbes, 8(6), 574–588. https://doi.org/10.1080/19490976.2017.1353848

Ramirez, J., Guarner, F., Bustos Fernandez, L., Maruy, A., Sdepanian, V. L., & Cohen, H. (2020). Antibiotics as Major Disruptors of Gut Microbiota. Frontiers in Cellular and Infection Microbiology, 10. https://doi.org/10.3389/fcimb.2020.572912

Rinninella, E., Raoul, P., Cintoni, M., Franceschi, F., Miggiano, G., Gasbarrini, A., & Mele, M. (2019). What is the Healthy Gut Microbiota Composition? A Changing Ecosystem across Age, Environment, Diet, and Diseases. Microorganisms, 7(1), 14. https://doi.org/10.3390/microorganisms7010014

Sabtu, N., Enoch, D. A., & Brown, N. M. (2015). Antibiotic resistance: what, why, where, when and how? British Medical Bulletin, ldv041. https://doi.org/10.1093/bmb/ldv041

Scheiman, J., Luber, J. M., Chavkin, T. A., MacDonald, T., Tung, A., Pham, L.-D., Wibowo, M. C., Wurth, R. C., Punthambaker, S., Tierney, B. T., Yang, Z., Hattab, M. W., Avila-Pacheco, J., Clish, C. B., Lessard, S., Church, G. M., & Kostic, A. D. (2019). Meta-omics analysis of elite athletes identifies a performance-enhancing microbe that functions via lactate metabolism. Nature Medicine, 25(7), 1104–1109. https://doi.org/10.1038/s41591-019-0485-4

Schwan, A. (1983). Relapsing Clostridium difficile enterocolitis cured by rectal infusion of homologous faeces. The Lancet, 322(8354), 845. https://doi.org/10.1016/S0140-6736(83)90753-5

Sekirov, I., Russell, S. L., Antunes, L. C. M., & Finlay, B. B. (2010). Gut Microbiota in Health and Disease. Physiological Reviews, 90(3), 859–904. https://doi.org/10.1152/physrev.00045.2009

Shreiner, A. B., Kao, J. Y., & Young, V. B. (2015). The gut microbiome in health and in disease. Current Opinion in Gastroenterology, 31(1), 69–75. https://doi.org/10.1097/MOG.0000000000000139

Spencer, C.N., McQuade, J.L., Gopalakrishnan, V., McCulloch, J.A., Vetizou, M., Cogdill, A.P., Khan, M.A.W., Zhang, X., (2021). Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response. Science, 374(6575), 1632-1640. https://doi.org/10.1126/science.aaz7015.

Tariq, R., Pardi, D. S., Tosh, P. K., Walker, R. C., Razonable, R. R., & Khanna, S. (2017a). Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection Reduces Recurrent Urinary Tract Infection Frequency. Clinical Infectious Diseases, 65(10), 1745–1747. https://doi.org/10.1093/cid/cix618

Tariq, R., Singh, S., Gupta, A., Pardi, D. S., & Khanna, S. (2017b). Association of Gastric Acid Suppression With Recurrent Clostridium difficile Infection. JAMA Internal Medicine, 177(6), 784. https://doi.org/10.1001/jamainternmed.2017.0212

Thursby, E., & Juge, N. (2017). Introduction to the human gut microbiota. Biochemical Journal, 474(11), 1823–1836. https://doi.org/10.1042/BCJ20160510

Vindigni, S. M., Zisman, T. L., Suskind, D. L., & Damman, C. J. (2016). The intestinal microbiome, barrier function, and immune system in inflammatory bowel disease: a tripartite pathophysiological circuit with implications for new therapeutic directions. Therapeutic Advances in Gastroenterology, 9(4), 606–625. https://doi.org/10.1177/1756283X16644242

Vrieze, A., Out, C., Fuentes, S., Jonker, L., Reuling, I., Kootte, R. S., van Nood, E., Holleman, F., Knaapen, M., Romijn, J. A., Soeters, M. R., Blaak, E. E., Dallinga-Thie, G. M., Reijnders, D., Ackermans, M. T., Serlie, M. J., Knop, F. K., Holst, J. J., van der Ley, C., … Nieuwdorp, M. (2014). Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity. Journal of Hepatology, 60(4), 824–831. https://doi.org/10.1016/j.jhep.2013.11.034

Xie, X., He, Y., Li, H., Yu, D., Na, L., Sun, T., Zhang, D., Shi, X., Xia, Y., Jiang, T., Rong, S., Yang, S., Ma, X., & Xu, G. (2019). Effects of prebiotics on immunologic indicators and intestinal microbiota structure in perioperative colorectal cancer patients. Nutrition, 61, 132–142. https://doi.org/10.1016/j.nut.2018.10.038

Yadav, M., & Chauhan, N. S. (2022). Microbiome therapeutics: exploring the present scenario and challenges. Gastroenterology Report, 10. https://doi.org/10.1093/gastro/goab046

Yang, L., Bajinka, O., Jarju, P. O., Tan, Y., Taal, A. M., & Ozdemir, G. (2021). The varying effects of antibiotics on gut microbiota. AMB Express, 11(1), 116. https://doi.org/10.1186/s13568-021-01274-w

Yassour, M., Vatanen, T., Siljander, H., Hämäläinen, A.-M., Härkönen, T., Ryhänen, S. J., Franzosa, E. A., Vlamakis, H., Huttenhower, C., Gevers, D., Lander, E. S., Knip, M., & Xavier, R. J. (2016). Natural history of the infant gut microbiome and impact of antibiotic treatment on bacterial strain diversity and stability. Science Translational Medicine, 8(343), 343ra81–343ra81. https://doi.org/10.1126/scitranslmed.aad0917

Zhou, Y., Xu, H., Huang, H., Li, Y., Chen, H., He, J., Du, Y., Chen, Y., Zhou, Y., & Nie, Y. (2019). Are There Potential Applications of Fecal Microbiota Transplantation beyond Intestinal Disorders? BioMed Research International, 2019, 1–11. https://doi.org/10.1155/2019/346975Zhou, Y., Xu, H., Huang, H., Li, Y., Chen, H., He, J., Du, Y., Chen, Y., Zhou, Y., & Nie, Y. (2019). Are There Potential Applications of Fecal Microbiota Transplantation beyond Intestinal Disorders? BioMed Research International, 2019, 1–11. https://doi.org/10.1155/2019/346975

Published
2023-12-30
How to Cite
AT, R., Mitra, A., Banerjee, A., Ilanchoorian, D., & Radhakrishnan, A. (2023). Current Understating of Gut Microbiome Alterations and Therapeutic Approaches for Improving Human Health. International Journal of Experimental Research and Review, 36, 253-264. https://doi.org/10.52756/ijerr.2023.v36.025
Section
Articles