HOST–MICROBIOME AND PHAGE INTERACTIONS IN HEALTH AND DISEASE: MECHANISTIC INSIGHTS AND THERAPEUTIC IMPLICATIONS: Microbiology and biochemstery

Rasha Hameed Jasim; Mustafa Abd- almajeed Abd-alkareem; Yasameen Hameed Jasim

doi:10.36526/biosense.v9i2.7408

Authors

Rasha Hameed Jasim Department of pathological analysis disease. College of Applied Sciences, Samarra University, Samarra , Iraq
Mustafa Abd- almajeed Abd-alkareem Department of pathological analysis disease. College of Applied Sciences, Samarra University, Samarra , Iraq
Yasameen Hameed Jasim Department of Applied Chemistry, College of Applied Sciences, Samarra University

DOI:

https://doi.org/10.36526/biosense.v9i2.7408

Keywords:

Microbiome, Phageome, Host-microbe interactions, Gut immunity, Dysbiosis, Microbial metabolites, Bacteriophages, Chronic disease.

Abstract

The human microbiome is a dynamic ecosystem, which has been found to combine microbial metabolism, immune regulation, and epithelial barrier functions to keep the host in a state of homeostasis. Disease related dysbiosis is increasingly being shown to be not merely a change in bacterial composition but a breakdown of the regulation of microbial ecosystems. At the heart of this regulation is the phageome that prevails in the gut virome and actively influences the dynamics of bacterial populations, functional capability and gene exchange. In this review, existing knowledge of mechanistic insights on host-microbiome and microbiome-phage interaction is synthesized, with focus on roles of microbial metabolites, immune sensing signals, and phage mediated ecology processes in shaping health and disease. We explain how disruptions of bacterial-phage interactions cause chronic inflammation, metabolic and immune pathology and therapy responses, and how the main methodological and conceptual problems restrict the current phageome studies. Incorporation of phage biology into microbiome models is vital to the future of ecosystem-based disease models, as well as to establish specific microbiome- and virome-directed treatments.

References

Abraham, C., & Medzhitov, R. (2011). Interactions between the host innate immune system and microbes in inflammatory bowel disease. Gastroenterology, 140(6), 1729-1737.

Abrahamsson, T. R., Jakobsson, H. E., Andersson, A. F., Björkstén, B., Engstrand, L., & Jenmalm, M. C. (2014). Low gut microbiota diversity in early infancy precedes asthma at school age. Clinical & Experimental Allergy, 44(6), 842-850.

Alkhalil, S. S. (2023). The role of bacteriophages in shaping bacterial composition and diversity in the human gut. Frontiers in Microbiology, 14, 1232413.

Araji, G., Maamari, J., Ahmad, F. A., Zareef, R., Chaftari, P., & Yeung, S. C. J. (2022). The emerging role of the gut microbiome in the cancer response to immune checkpoint inhibitors: a narrative review. Journal of Immunotherapy and Precision Oncology, 5(1), 13-25.

Borrego-Ruiz, A., & Borrego, J. J. (2025). The gut Microbiome in human obesity: a comprehensive review. Biomedicines, 13(9), 2173.

Cai, X., Afthab, M., Hambo, S., Salem, M., Bhitale, R. R., & Harb, H. (2025). From allergens to epigenetics: how histone acetylation shapes immune gene expression in allergic diseases. Epigenomics, 17(15), 1091-1105.

Castledine, M., & Buckling, A. (2024). Critically evaluating the relative importance of phage in shaping microbial community composition. Trends in Microbiology, 32(10), 957-969.

Cebi, M., & Yilmaz, Y. (2025). Epithelial barrier hypothesis in the context of nutrition, microbial dysbiosis, and immune dysregulation in metabolic dysfunction-associated steatotic liver. Frontiers in Immunology, 16, 1575770.

Cenit, M. C., Sanz, Y., & Codoñer-Franch, P. (2017). Influence of gut microbiota on neuropsychiatric disorders. World journal of gastroenterology, 23(30), 5486.

Chen, Q., Ma, X., Li, C., Shen, Y., Zhu, W., Zhang, Y., ... & Liu, C. (2021). Enteric phageome alterations in patients with type 2 diabetes. Frontiers in cellular and infection microbiology, 10, 575084.

Chen, R., Zou, J., Chen, J., Zhong, X., Kang, R., & Tang, D. (2025). Pattern recognition receptors: function, regulation and therapeutic potential. Signal Transduction and Targeted Therapy, 10(1), 216.

Chidambaram, S. B., Rathipriya, A. G., Mahalakshmi, A. M., Sharma, S., Hediyal, T. A., Ray, B., ... & Monaghan, T. M. (2022). The influence of gut dysbiosis in the pathogenesis and management of ischemic stroke. Cells, 11(7), 1239.

Cianci, R., Caldarelli, M., Brani, P., Bosi, A., Ponti, A., Giaroni, C., & Baj, A. (2025). Cytokines Meet Phages: A Revolutionary Pathway to Modulating Immunity and Microbial Balance. Biomedicines, 13(5), 1202.

Coretti, L., Buommino, E., & Lembo, F. (2024). The aryl hydrocarbon receptor pathway: a linking bridge between the gut microbiome and neurodegenerative diseases. Frontiers in Cellular Neuroscience, 18, 1433747.

D’Aquila, P., Lynn Carelli, L., De Rango, F., Passarino, G., & Bellizzi, D. (2020). Gut microbiota as important mediator between diet and DNA methylation and histone modifications in the host. Nutrients, 12(3), 597.

DiMattia, Z., Damani, J. J., Van Syoc, E., & Rogers, C. J. (2024). Effect of probiotic supplementation on intestinal permeability in overweight and obesity: a systematic review of randomized controlled trials and animal studies. Advances in Nutrition, 15(1), 100162.

Domingues, R. G., & Hepworth, M. R. (2020). Immunoregulatory sensory circuits in group 3 innate lymphoid cell (ILC3) function and tissue homeostasis. Frontiers in immunology, 11, 116.

Duan, H., Wang, L., Huangfu, M., & Li, H. (2023). The impact of microbiota-derived short-chain fatty acids on macrophage activities in disease: Mechanisms and therapeutic potentials. Biomedicine & Pharmacotherapy, 165, 115276.

Durack, J., & Lynch, S. V. (2019). The gut microbiome: Relationships with disease and opportunities for therapy. The Journal of experimental medicine, 216(1), 20.

Effendi, R. M. R. A., Anshory, M., Kalim, H., Dwiyana, R. F., Suwarsa, O., Pardo, L. M., ... & Thio, H. B. (2022). Akkermansia muciniphila and Faecalibacterium prausnitzii in immune-related diseases. Microorganisms, 10(12), 2382.

Federici, S., Nobs, S. P., & Elinav, E. (2021). Phages and their potential to modulate the microbiome and immunity. Cellular & molecular immunology, 18(4), 889-904.

Flores, C., Millard, S., & Seekatz, A. M. (2025). Bridging Ecology and Microbiomes: Applying Ecological Theories in Host-associated Microbial Ecosystems.Current Clinical Microbiology Reports,12(1), 9.

Fusco, W., Lorenzo, M. B., Cintoni, M., Porcari, S., Rinninella, E., Kaitsas, F., ... & Ianiro, G. (2023). Short-chain fatty-acid-producing bacteria: key components of the human gut microbiota. Nutrients, 15(9), 2211.

Geng, J., Ni, Q., Sun, W., Li, L., & Feng, X. (2022). The links between gut microbiota and obesity and obesity related diseases. Biomedicine & Pharmacotherapy, 147, 112678.

Godsil, M., Ritz, N. L., Venkatesh, S., & Meeske, A. J. (2025). Gut phages and their interactions with bacterial and mammalian hosts. Journal of bacteriology, 207(2), e00428-24.

Gong, D., Gong, X., Wang, L., Yu, X., & Dong, Q. (2016). Involvement of reduced microbial diversity in inflammatory bowel disease. Gastroenterology Research and Practice, 2016(1), 6951091.

Goodrich, J. K., Davenport, E. R., Clark, A. G., & Ley, R. E. (2017). The relationship between the human genome and microbiome comes into view. Annual review of genetics, 51, 413-433.

Horta-Baas, G., Romero-Figueroa, M. D. S., Montiel-Jarquín, A. J., Pizano-Zárate, M. L., García-Mena, J., & Ramírez-Durán, N. (2017). Intestinal dysbiosis and rheumatoid arthritis: a link between gut microbiota and the pathogenesis of rheumatoid arthritis. Journal of immunology research, 2017(1), 4835189.

Jankowski, W., Mizielińska, M., & Nawrotek, P. (2025). Microbiome and Phageome: Key Factors in Host Organism Function and Disease Prevention in the Context of Microbiome Transplants. Applied Sciences, 15(10), 5330.

Jdeed, G., Kravchuk, B., & Tikunova, N. V. (2025). Factors Affecting Phage–Bacteria Coevolution Dynamics. Viruses, 17(2), 235.

Jian, E., Wang, M., Zhang, Z., Heng, Y., Zhang, C., Chen, Q., ... & Cai, P. (2025). The metabolic endotoxemia and gut microbiota: research trajectories and hot trends across the centuries (1999-2024). Frontiers in Microbiology, 16, 1634803.

Khalil, M., Di Ciaula, A., Mahdi, L., Jaber, N., Di Palo, D. M., Graziani, A., ... & Portincasa, P. (2024). Unraveling the role of the human gut microbiome in health and diseases. Microorganisms, 12(11), 2333.

Kumar Singh, A., Cabral, C., Kumar, R., Ganguly, R., Kumar Rana, H., Gupta, A., ... & Pandey, A. K. (2019). Beneficial effects of dietary polyphenols on gut microbiota and strategies to improve delivery efficiency.Nutrients,11(9), 2216.

Kumar, A., Sakhare, K., Bhattacharya, D., Chattopadhyay, R., Parikh, P., Narayan, K. P., & Mukherjee, A. (2022). Communication in non-communicable diseases (NCDs) and role of immunomodulatory nutraceuticals in their management. Frontiers in Nutrition, 9, 966152.

Lange, O., Proczko-Stepaniak, M., & Mika, A. (2023). Short-chain fatty acids—a product of the microbiome and its participation in two-way communication on the microbiome-host mammal line. Current obesity reports, 12(2), 108-126.

Lee, J. H., Shin, J. H., Kim, J. Y., Ju, H. J., & Kim, G. M. (2024). Exploring the role of gut microbiota in patients with alopecia areata. International Journal of Molecular Sciences, 25(8), 4256.

Mirzaei, R., Bouzari, B., Hosseini-Fard, S. R., Mazaheri, M., Ahmadyousefi, Y., Abdi, M., ... & Karampoor, S. (2021). Role of microbiota-derived short-chain fatty acids in nervous system disorders. Biomedicine & Pharmacotherapy, 139, 111661.

Mo, C., Lou, X., Xue, J., Shi, Z., Zhao, Y., Wang, F., & Chen, G. (2024). The influence of Akkermansia muciniphila on intestinal barrier function. Gut Pathogens, 16(1), 41.

Nabi-Afjadi, M., Teymouri, S., Monfared, F. N., Varnosfaderani, S. M. N., & Halimi, H. (2023). The human gut phageome: identification and roles in the diseases. Journal of Cellular Signaling, 4(3), 128-141.

Niazi, S. K. (2025). Bacteriophage therapy: discovery, development, and FDA approval pathways. Pharmaceuticals, 18(8), 1115.

Pan, Y., Deng, Y., Yang, H., & Yu, M. (2025). The aryl hydrocarbon receptor: A promising target for intestinal fibrosis therapy. Pharmacological Research, 107909.

Pathak, S., & Banerjee, A. (Eds.). (2024). Gut Microbiome and Brain Ageing. Springer.

Ponce-Lopez, T. (2025). Peripheral Inflammation and Insulin Resistance: Their Impact on Blood–Brain Barrier Integrity and Glia Activation in Alzheimer’s Disease. International Journal of Molecular Sciences, 26(9), 4209.

Qin, Y., & Wade, P. A. (2018). Crosstalk between the microbiome and epigenome: messages from bugs. The Journal of Biochemistry, 163(2), 105-112.

Ranveer, S. A., Dasriya, V., Ahmad, M. F., Dhillon, H. S., Samtiya, M., Shama, E., ... & Puniya, A. K. (2024). Positive and negative aspects of bacteriophages and their immense role in the food chain. npj Science of Food, 8(1), 1.

Rosendo-Silva, D., Viana, S., Carvalho, E., Reis, F., & Matafome, P. (2023). Are gut dysbiosis, barrier disruption, and endotoxemia related to adipose tissue dysfunction in metabolic disorders? Overview of the mechanisms involved. Internal and Emergency Medicine, 18(5), 1287-1302.

Rowland, I., Gibson, G., Heinken, A., Scott, K., Swann, J., Thiele, I., & Tuohy, K. (2018). Gut microbiota functions: metabolism of nutrients and other food components. European journal of nutrition, 57(1), 1-24.

Safarchi, A., Al-Qadami, G., Tran, C. D., & Conlon, M. (2025). Understanding dysbiosis and resilience in the human gut microbiome: Biomarkers, interventions, and challenges. Frontiers in Microbiology, 16, 1559521.

Sanam, M., Hossain, C. F. T. Z., Hyder, T. B., Tarannum, R., Oishi, J. F., Rahman, K. M. M., ... & Fakruddin, M. (2025). Bridging two worlds: Host Microbiota crosstalk in health and dysregulation.Innate Immunity,31, 17534259251392993.

Shamash, M., & Maurice, C. F. (2022). Phages in the infant gut: a framework for virome development during early life. The ISME journal, 16(2), 323-330.

Sharon, G., Cruz, N. J., Kang, D. W., Gandal, M. J., Wang, B., Kim, Y. M., ... & Mazmanian, S. K. (2019). Human gut microbiota from autism spectrum disorder promote behavioral symptoms in mice. Cell, 177(6), 1600-1618.

Shetty, S. A., Kostopoulos, I., Geerlings, S. Y., Smidt, H., de Vos, W. M., & Belzer, C. (2022). Dynamic metabolic interactions and trophic roles of human gut microbes identified using a minimal microbiome exhibiting ecological properties. The ISME Journal, 16(9), 2144-2159.

Shkoporov, A. N., Clooney, A. G., Sutton, T. D., Ryan, F. J., Daly, K. M., Nolan, J. A., ... & Hill, C. (2019). The human gut virome is highly diverse, stable, and individual specific. Cell host & microbe, 26(4), 527-541.

Smith, L., Goldobina, E., Govi, B., & Shkoporov, A. N. (2023). Bacteriophages of the order Crassvirales: what do we currently know about this keystone component of the human gut virome?. Biomolecules, 13(4), 584.

Tang, X., Liao, H. P., Gao, J. T., Yang, Q. E., Rensing, C., & Zhou, S. G. (2025). Omnipresent Allies: The Role of Temperate Phages in Microbial Adaptation Across Ecosystems. Environmental Microbiology, 27(11), e70204.

Torres-Barceló, C. (2018). The disparate effects of bacteriophages on antibiotic-resistant bacteria. Emerging microbes & infections, 7(1), 1-12.

Tzani-Tzanopoulou, P., Skliros, D., Megremis, S., Xepapadaki, P., Andreakos, E., Chanishvili, N., ... & Papadopoulos, N. G. (2021). Interactions of bacteriophages and bacteria at the airway mucosa: new insights into the pathophysiology of asthma. Frontiers in Allergy, 1, 617240.

Ullah, H., Arbab, S., Tian, Y., Chen, Y., Liu, C. Q., Li, Q., & Li, K. (2024). Crosstalk between gut microbiota and host immune system and its response to traumatic injury. Frontiers in immunology, 15, 1413485.

Ullah, K., Kanwar, R., Ali, S., Uddin, S., Izza, I., Ahmad, I., ... & Chen, C. C. (2025). Gut Virome and Aging: Phage-Driven Microbial Stability and Immune Modulation. Aging and Disease.

Vaziri, Y., Olia, J. B. H., Avci, C. B., & Nourazarian, A. (2025). Molecular mechanisms of gut microbiota dysbiosis and metabolites in Alzheimer’s disease pathogenesis: implications for precision therapeutics. Molecular Brain.

Voigt, E., Rall, B. C., Chatzinotas, A., Brose, U., & Rosenbaum, B. (2021). Phage strategies facilitate bacterial coexistence under environmental variability. PeerJ, 9, e12194.

Wang, R., Lan, C., Benlagha, K., Camara, N. O. S., Miller, H., Kubo, M., ... & Liu, C. (2024). The interaction of innate immune and adaptive immune system. MedComm, 5(10), e714.

Wiertsema, S. P., van Bergenhenegouwen, J., Garssen, J., & Knippels, L. M. (2021). The interplay between the gut microbiome and the immune system in the context of infectious diseases throughout life and the role of nutrition in optimizing treatment strategies. Nutrients, 13(3), 886.

Wu, J., Wang, S., Zheng, B., Qiu, X., Wang, H., & Chen, L. (2021). Modulation of gut microbiota to enhance effect of checkpoint inhibitor immunotherapy. Frontiers in Immunology, 12, 669150.

Xu, Z., Wang, T., Wang, Y., Li, Y., Sun, Y., & Qiu, H. J. (2025). Short-chain fatty acids: key antiviral mediators of gut microbiota. Frontiers in Immunology, 16, 1614879.

Yang, W., & Cong, Y. (2021). Gut microbiota-derived metabolites in the regulation of host immune responses and immune-related inflammatory diseases. Cellular & molecular immunology, 18(4), 866-877.

Yu, X., Cheng, L., Yi, X., Li, B., Li, X., Liu, X., ... & Kong, X. (2024). Gut phageome: challenges in research and impact on human microbiota. Frontiers in Microbiology, 15, 1379382.

Zalewska-Piątek, B. (2023). Phage therapy—challenges, opportunities and future prospects. Pharmaceuticals, 16(12), 1638.

Zhang, W., Xiang, Y., Ren, H., Liu, Y., Wang, Q., Ran, M., ... & Yan, M. (2025). The tumor microbiome in cancer progression: mechanisms and therapeutic potential. Molecular Cancer, 24(1), 195.

Zhang, Y., & Wang, R. (2023). The human gut phageome: composition, development, and alterations in disease. Frontiers in Microbiology, 14, 1213625.