Role of immunological biomarkers in the alterations of the intestinal microbiota
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Published:
Jul 18, 2025
Keywords:
Gut microbiota. Immunological biomarkers. Immune response Dysbiosis Inflammatory bowel diseases
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Abstract
Introduction: The composition of the intestinal microbiota is closely related to the modulation of immune system activity. However, alterations in this composition (dysbiosis) compromise biological functions and bacterial balance and are associated with pathologies such as obesity, cancer, inflammatory disorders, and even neurological conditions. In such cases, immunological markers allow for the evaluation of inflammatory processes and the functional state of microbiota. Objective: Describe the impact of immunological biomarkers on alterations of the intestinal microbiota through a literature review. Methodology: The information was gathered from studies published between 2020 and 2025. The search for articles was conducted in the scientific databases PubMed, Scopus, and Web of Science. Studies published in both Spanish and English were included. Results: Dysbiosis leads to an increase in opportunistic and pathogenic bacteria, triggering the host's immune response by stimulating the production of proinflammatory cytokines. Thus, IL-6, TNF-a, IL-1ß, IL-8, and fecal calprotectin were the most relevant immunological markers presented in this study, as they can assess mucosal damage and the progression of the inflammatory process. However, markers such as C-reactive protein, due to their lower specificity, have limited diagnostic value. Conclusion: This article summarizes the diagnostic value of immunological markers in microbial imbalance scenarios and their interaction with immune response activation associated with inflammatory disorders, infections, cancer, and neurological diseases. In this way, diagnostic tools are presented that offer new perspectives for the clinical management of patients. General Area of Study: Health Sciences Specific area of study: Clinical Laboratory Type of study: Narrative literature review
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Tubón Arcos, G. B., & Proaño Pérez M. E. (2025). Role of immunological biomarkers in the alterations of the intestinal microbiota . Anatomía Digital, 8(3), 66-85. https://doi.org/10.33262/anatomiadigital.v8i3.3456
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Articulos de revisión bibliográfica
References
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19. Huang C, Feng S, Huo F, Liu H. Effects of four antibiotics on the diversity of the intestinal microbiota. Microbiology Spectrum [Internet]. 2022 [cited 2025 May 17];10(2): e01904. Available from: https://journals.asm.org/doi/10.1128/spectrum.01904-21
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21. Blagojevic C, Brown KA, Diong C, Fridman DJ, Johnstone J, Langford BJ, et al. Long-term risk of infection among patients colonized with antimicrobial-resistant pathogens: a population-wide cohort study. Open Forum Infectious Diseases [Internet]. 2024 [cited 2025 May 23];11(12): ofae712. Available from: https://academic.oup.com/ofid/article/11/12/ofae712/7914450
22. Patin NV, Peña-Gonzalez A, Hatt JK, Moe C, Kirby A, Konstantinidis KT. The role of the gut microbiome in resisting norovirus infection as revealed by a human challenge study. Revista de la American Society for Microbiology [Internet]. 2020 [cited May 23]; 11(6):1–15. Available from: https://journals.asm.org/doi/10.1128/mbio.02634-20
23. Yan Q, Chen Y, Gao EB, Lu Y, Wu J, Qiu H. The characteristics of intestinal microflora in infants with rotavirus enteritis, changes in microflora before and after treatment and their clinical values. Scientific Reports [Internet]. 2025 [cited 2025 May 23];15(4312). Available from: https://www.nature.com/articles/s41598-025-88312-w
24. Li Z, Chen J, Li Y, Li L, Zhan Y, Yang J, et al. Impact of SARS-CoV-2 infection on respiratory and gut microbiome stability: a metagenomic investigation in long-term-hospitalized COVID-19 patients. NPJ Biofilms & Microbiomes [Internet]. 2024 [cited 2025 May 14];10(126). Available from: https://www.nature.com/articles/s41522-024-00596-4
25. Krawiec P, Pac-Kożuchowska E. Serum interleukin 17A and interleukin 17F in children with inflammatory bowel disease. Scientific Reports [Internet]. 2020 [cited 2025 May 14];10(12617). Available from: https://www.nature.com/articles/s41598-020-69567-x#:~:text=In%20conclusion%20we%20demonstrated%20that,the%20pathogenesis%20of%20paediatric%20IBD
26. Chen HZ, Zeng YY, Cai GX, Gu WD, Yang YL. Differential analysis of serum immunology and gut microbiota in patients with gastrointestinal diseases. Frontiers in Microbiology [Internet]. 2024 [cited 2025 May 24];15. Available from: https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2024.1323842/full
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28. Higgins KV, Woodie LN, Hallowell H, Greene MW, Schwartz EH. Integrative longitudinal analysis of metabolic phenotype and microbiota changes during the development of obesity. Frontiers in Cellular and Infection Microbiology [Internet]. 2021 [cited 2025 May 14];11. Available from: https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.671926/full
29. Jacobs JP, Gupta A, Bhatt RR, Brawer J, Gao K, Tillisch K, et al. Cognitive behavioral therapy for irritable bowel syndrome induces bidirectional alterations in the brain-gut-microbiome axis associated with gastrointestinal symptom improvement. Microbiome [Internet]. 2021 [cited 2025 May 14]; 9(236). Available from: https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-021-01188-6
30. Kruger K, Myeonghyun Y, van der Wielen N, Kok DE, Hooiveld GJ, Keshtkar S, et al. Evaluation of inter- and intra-variability in gut health markers in healthy adults using an optimized fecal sampling and processing method. Scientific Reports [Internet]. 2024 [cited 2025 May 18];14(24580). Available from: https://www.nature.com/articles/s41598-024-75477-z
2. Tian L, Wang XW, Wu AK, Fan Y, Friedman J, Dahlin A, et al. Deciphering functional redundancy in the human microbiome. Nature Communications [Internet]. 2020 [cited 2025 May 14];11(6217). Available from: https://www.nature.com/articles/s41467-020-19940-1
3. Shao XX, Fang LY, Guo XR, Wang WZ, Shi RX, Lin DP. Knowledge, attitude, and practice of patients living with inflammatory bowel disease: A cross-sectional study. World Journal of Gastroenterology [Internet]. 2023 [cited 2025 May 14]; 29(43):5818-5833. Available from: https://www.wjgnet.com/1007-9327/full/v29/i43/5818.htm
4. Naqvi SA, Taylor LM, Panaccione R, Ghosh S, Barkema HW, Hotte N, et al. Dietary patterns, food groups and nutrients in Crohn’s disease: associations with gut and systemic inflammation. Scientific reports [Internet]. 2021 [cited 2025 May 14];11(1674). Available from: https://www.nature.com/articles/s41598-020-80924-8
5. Cao Z, Fan D, Sun Y, Huang Z, Li Y, Su R, et al. The gut ileal mucosal virome is disturbed in patients with Crohn’s disease and exacerbates intestinal inflammation in mice. Nature Communications [Internet]. 2024 [cited 2025 May 14];15(1638). Available from: https://www.nature.com/articles/s41467-024-45794-y
6. Li R, Wang F, Dang S, Yao M, Zhang W, Wang J. Integrated 16S rRNA Gene sequencing and metabolomics analysis to investigate the important role of osthole on gut microbiota and serum metabolites in neuropathic pain mice. Frontiers in Physiology [Internet]. 2022 [cited 2025 May 14];13. Available from: https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2022.813626/full
7. Wu L, Xie X, Li Y, Liang T, Zhong H, Ma J, et al. Metagenomics-based analysis of the age-related cumulative effect of antibiotic resistance genes in gut microbiota. Antibiotics [Internet]. 2021 [cited 2025 May 14];10(8): 1006. Available from: https://www.mdpi.com/2079-6382/10/8/1006
8. Li Y, Shi Z, Zhang X, Ren H, Ji H, Yang F, et al. Metagenomic analysis revealing links between age, gut microbiota and bone loss in Chinese adults. NPJ Metabolic Health and Disease [Internet]. 2025 [cited 2025 May 14];3(18). Available from: https://www.nature.com/articles/s44324-025-00060-7
9. Chen L, He FJ, Dong Y, Huang Y, Wang C, Harshfield GA, et al. Modest sodium reduction increases circulating short-chain fatty acids in untreated hypertensives: a randomized, double-blind, placebo-controlled trial. Hypertension [Internet]. 2020 [cited 2025 May 14];76(1):73–79. Available from: https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.120.14800
10. Cao Z, Zuo W, Wang L, Chen J, Qu Z, Jin F, et al. Spatial profiling of microbial communities by sequential FISH with error-robust encoding. Nature Communications [Internet]. 2023 [cited 2025 May 14];14(1477). Available from: https://www.nature.com/articles/s41467-023-37188-3
11. Becattini S, Littmann ER, Seok R, Amoretti L, Fontana E, Wright R, et al. Enhancing mucosal immunity by transient microbiota depletion. Nature Communications [Internet]. 2020 [cited 2024 May 14]; 11(4475). Available from: https://www.nature.com/articles/s41467-020-18248-4
12. Kroon S, Malcic D, Weidert L, Bircher L, Boldt L, Christen P, et al. Sublethal systemic LPS in mice enables gut-luminal pathogens to bloom through oxygen species-mediated microbiota inhibition. Nature Communications [Internet]. 2025 [cited 2025 May 14];16(2760). Available from: https://www.nature.com/articles/s41467-025-57979-0
13. Manor O, Dai CL, Kornilov SA, Smith B, Price ND, Lovejoy JC, et al. Health and disease markers correlate with gut microbiome composition across thousands of people. Nature Communications [Internet]. 2020 [cited 2025 May 14];11(5206). Available from: https://www.nature.com/articles/s41467-020-18871-1
14. Álvarez J, Fernández Real JM, Guarner F, Gueimonde M, Rodríguez JM, Saenz de Pipaon M, et al. Microbiota intestinal y salud. Gastroenterología y Hepatología [Internet]. 2023 [citado 14 mayo 2025];44(8): 519-535. Disponible en: https://www.sciencedirect.com/science/article/pii/S0210570521000583?via%3Dihub
15. Gupta S, Gupta SL, Singh A, Oswal N, Bal V, Rath S, et al. IgA determines bacterial composition in the gut. Crohns & Colitis 360 [Internet]. 2023 [cited 2025 May 14];5(3). Available from: https://academic.oup.com/crohnscolitis360/article/5/3/otad030/7180212
16. Kang S, Yun J, Park HY, Lee JE. Analytical factors for eight short-chain fatty acid analyses in mouse feces through headspace solid-phase microextraction–triple quadrupole gas chromatography tandem mass spectrometry. Analytical and Bioanalytical Chemistry [Internet]. 2023 [cited 2025 May 14];415(25): 6227–6235. Available from: https://link.springer.com/article/10.1007/s00216-023-04895-1
17. Syed Khaja AS, Binsaleh NK, Beg MMA, Ashfaq F, Khan MI, Almutairi MG, et al. Clinical importance of cytokine (IL-6, IL-8, and IL-10) and vitamin D levels among patients with Type-1 diabetes. Scientific Reports [Internet]. 2024 [cited 2025 May 14];14(24225). Available from: https://www.nature.com/articles/s41598-024-73737-6#:~:text=These%20results%20showed%20that%20elevated,could%20serve%20as%20predictive%20indicators
18. Wastyk HC, Fragiadakis GK, Perelman D, Dahan D, Merrill BD, Yu FB, et al. Gut-microbiota-targeted diets modulate human immune status. Cell [Internet]. 2021 [cited 2025 May 17]; 184(16): 4137-4153. Available from: https://www.cell.com/cell/fulltext/S0092-8674(21)00754-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867421007546%3Fshowall%3Dtrue
19. Huang C, Feng S, Huo F, Liu H. Effects of four antibiotics on the diversity of the intestinal microbiota. Microbiology Spectrum [Internet]. 2022 [cited 2025 May 17];10(2): e01904. Available from: https://journals.asm.org/doi/10.1128/spectrum.01904-21
20. Herrera G, Vega L, Patarroyo MA, Ramírez JD, Muñoz M. Gut microbiota composition in health-care facility-and community-onset diarrheic patients with Clostridioides difficile infection. Scientific Reports [Internet]. 2021 [cited 2025 May 23];11(10849). Available from: https://www.nature.com/articles/s41598-021-90380-7
21. Blagojevic C, Brown KA, Diong C, Fridman DJ, Johnstone J, Langford BJ, et al. Long-term risk of infection among patients colonized with antimicrobial-resistant pathogens: a population-wide cohort study. Open Forum Infectious Diseases [Internet]. 2024 [cited 2025 May 23];11(12): ofae712. Available from: https://academic.oup.com/ofid/article/11/12/ofae712/7914450
22. Patin NV, Peña-Gonzalez A, Hatt JK, Moe C, Kirby A, Konstantinidis KT. The role of the gut microbiome in resisting norovirus infection as revealed by a human challenge study. Revista de la American Society for Microbiology [Internet]. 2020 [cited May 23]; 11(6):1–15. Available from: https://journals.asm.org/doi/10.1128/mbio.02634-20
23. Yan Q, Chen Y, Gao EB, Lu Y, Wu J, Qiu H. The characteristics of intestinal microflora in infants with rotavirus enteritis, changes in microflora before and after treatment and their clinical values. Scientific Reports [Internet]. 2025 [cited 2025 May 23];15(4312). Available from: https://www.nature.com/articles/s41598-025-88312-w
24. Li Z, Chen J, Li Y, Li L, Zhan Y, Yang J, et al. Impact of SARS-CoV-2 infection on respiratory and gut microbiome stability: a metagenomic investigation in long-term-hospitalized COVID-19 patients. NPJ Biofilms & Microbiomes [Internet]. 2024 [cited 2025 May 14];10(126). Available from: https://www.nature.com/articles/s41522-024-00596-4
25. Krawiec P, Pac-Kożuchowska E. Serum interleukin 17A and interleukin 17F in children with inflammatory bowel disease. Scientific Reports [Internet]. 2020 [cited 2025 May 14];10(12617). Available from: https://www.nature.com/articles/s41598-020-69567-x#:~:text=In%20conclusion%20we%20demonstrated%20that,the%20pathogenesis%20of%20paediatric%20IBD
26. Chen HZ, Zeng YY, Cai GX, Gu WD, Yang YL. Differential analysis of serum immunology and gut microbiota in patients with gastrointestinal diseases. Frontiers in Microbiology [Internet]. 2024 [cited 2025 May 24];15. Available from: https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2024.1323842/full
27. Tajik N, Frech M, Schulz O, Schälter F, Lucas S, Azizov V, et al. Targeting zonulin and intestinal epithelial barrier function to prevent onset of arthritis. Nature Communications [Internet]. 2020 [cited 2025 May 14]; 11(1995). Available from: https://www.nature.com/articles/s41467-020-15831-7
28. Higgins KV, Woodie LN, Hallowell H, Greene MW, Schwartz EH. Integrative longitudinal analysis of metabolic phenotype and microbiota changes during the development of obesity. Frontiers in Cellular and Infection Microbiology [Internet]. 2021 [cited 2025 May 14];11. Available from: https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.671926/full
29. Jacobs JP, Gupta A, Bhatt RR, Brawer J, Gao K, Tillisch K, et al. Cognitive behavioral therapy for irritable bowel syndrome induces bidirectional alterations in the brain-gut-microbiome axis associated with gastrointestinal symptom improvement. Microbiome [Internet]. 2021 [cited 2025 May 14]; 9(236). Available from: https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-021-01188-6
30. Kruger K, Myeonghyun Y, van der Wielen N, Kok DE, Hooiveld GJ, Keshtkar S, et al. Evaluation of inter- and intra-variability in gut health markers in healthy adults using an optimized fecal sampling and processing method. Scientific Reports [Internet]. 2024 [cited 2025 May 18];14(24580). Available from: https://www.nature.com/articles/s41598-024-75477-z