AccScience Publishing / MI / Online First / DOI: 10.36922/MI025490127
REVIEW ARTICLE

Microbial matchmakers: How microbiome dysbiosis fans the flames of chronic inflammation

Jahanara Abdul Hannan1 Md. Asaduzzaman Shishir2 Kazi Fahmida Rahman1 Kazi Samia Pial1 Kazi Md. Mostafizur Rahman1 S.M. Bakhtiar Ul Islam1 Nayeema Bulbul1 Jinath Sultana Jime1 Ashrafus Safa3 Md. Fakruddin1*
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1 Department of Biochemistry and Microbiology, North South University, Bashundhara R/A, Dhaka, Bangladesh
2 Department of Microbiology, Dhaka International University, Badda, Dhaka, Bangladesh
3 Department of Life Sciences, School of Environment and Life Sciences, Independent University Bangladesh, Bashundhara R/A, Dhaka
Received: 3 December 2024 | Revised: 17 January 2026 | Accepted: 23 January 2026 | Published online: 24 April 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

The human gut microbiome plays a critical role in maintaining immune homeostasis and metabolic health. Aging is accompanied by significant shifts in microbial composition—termed dysbiosis—which contribute to a proinflammatory state known as “inflammaging.” This chronic, low-grade inflammation underlies numerous age-associated diseases, including atherosclerosis, neurodegeneration, and metabolic syndrome. This review aims to explore the mechanisms through which age-related microbial dysbiosis contributes to chronic inflammation and to examine current therapeutic strategies targeting the microbiome to mitigate inflammaging. A comprehensive literature review was conducted using PubMed-indexed articles from 2000 to 2025. Studies addressing microbiome composition in aging, microbial metabolite pathways, immune modulation, and interventions including probiotics, dietary modifications, and fecal microbiota transplantation (FMT) were included. Aging is associated with reduced microbial diversity, a decline in beneficial taxa such as Faecalibacterium prausnitzii, and enrichment of proinflammatory taxa like Proteobacteria. This dysbiosis impairs gut barrier function, promoting systemic translocation of microbial products such as lipopolysaccharide (LPS). Metabolites like short-chain fatty acids (SCFAs) are diminished, leading to decreased regulatory T cell (Treg) function and epithelial integrity. Conversely, elevated levels of trimethylamine N-oxide (TMAO) and LPS activate pattern recognition receptors, triggering innate immune pathways (e.g., NF-κB, NLRP3 inflammasome) that perpetuate chronic inflammation. Interventions such as probiotic supplementation and FMT from young donors show promise in reversing dysbiosis, restoring microbial metabolites, and attenuating inflammatory responses in both animal models and early human trials. Understanding the gut-immune-metabolite axis offers new opportunities to intervene in age-related diseases through targeted microbiome modulation.

Keywords
Microbiome
Inflammaging
Dysbiosis
Short-chain fatty acids
Trimethylamine N-oxide
Lipopolysaccharide
Funding
None.
Conflict of interest
The authors declare they have no competing interests.
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