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

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

Acknowledgments

None.

Funding

None.

Conflict of interest

The authors declare they have no competing interests.

Author contributions

Conceptualization: Md. Fakruddin, Kazi Md. Mostafizur Rahman, Kazi Fahmida Rahman, Nayeema Bulbul, Jinath Sultana Jime

Visualization: Md. Fakruddin, Kazi Md. Mostafizur Rahman, Kazi Samia Pial, Nayeema Bulbul, Jinath Sultana Jime

Writing-original draft: Jahanara Abdul Hannan, SM Bakhtiar Ul Islam, Md. Fakruddin, Md. Asaduzzaman Shishir

Writing-review & editing: Nayeema Bulbul, Jinath Sultana Jime, Ashrafus Safa

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data

Not applicable.

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