Neuroinflammation in neurodegenerative disorders: Activation of microglia by microbial infection

Tianshi Jiang; Kaili Zhu; Guangli Kang; Guojun Wu; Yurong Tan; Tianshi Jiang; Kaili Zhu; Guangli Kang; Guojun Wu; Yurong Tan

doi:10.3934/molsci.2025013

AIMS Molecular Science

2025, Volume 12, Issue 3: 198-215. doi: 10.3934/molsci.2025013

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Review

Neuroinflammation in neurodegenerative disorders: Activation of microglia by microbial infection

Department of Medical Microbiology, Central South University Changsha, Hunan Province, China
These authors contributed equally to this work.

Received: 13 May 2025 Revised: 14 June 2025 Accepted: 30 June 2025 Published: 09 July 2025

Neurodegenerative disorders present a significant global health challenge. Neuroinflammation, which is a frequent occurrence of these diseases, may serve as an initial trigger. Emerging evidence suggests that microglia play a pivotal role as mediators of inflammation in the central nervous system. Disordered activation skews predominantly towards the M1 phenotype, which leads to neurotoxicity and neuroinflammation. Identifying the triggers of microglial activation is crucial to refine the therapeutic strategies for neurodegenerative diseases. Based on epidemiological, biological, and functional data, we observed a strong correlation between chronic microbial infection and microglial activation. This review outlines three potential inter-organ communication routes for infectious microbes in microglial activation—the gut-brain axis, the lung-brain axis, and the nose-brain axis—thus emphasizing the interaction between microglia and inflammation and proving that neuroinflammation is a significant factor in pathogen-induced neurodegenerative diseases. Collectively, we propose that therapies which target relevant inflammatory mediators, along with antibiotics that target neuropathogens, could potentially alleviate neuroinflammation and treat neurodegenerative diseases.
- neurodegenerative diseases,
- neuroinflammation,
- microbial infection,
- microglial activation,
- human microbiome
Citation: Tianshi Jiang, Kaili Zhu, Guangli Kang, Guojun Wu, Yurong Tan. Neuroinflammation in neurodegenerative disorders: Activation of microglia by microbial infection[J]. AIMS Molecular Science, 2025, 12(3): 198-215. doi: 10.3934/molsci.2025013

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Abstract

Neurodegenerative disorders present a significant global health challenge. Neuroinflammation, which is a frequent occurrence of these diseases, may serve as an initial trigger. Emerging evidence suggests that microglia play a pivotal role as mediators of inflammation in the central nervous system. Disordered activation skews predominantly towards the M1 phenotype, which leads to neurotoxicity and neuroinflammation. Identifying the triggers of microglial activation is crucial to refine the therapeutic strategies for neurodegenerative diseases. Based on epidemiological, biological, and functional data, we observed a strong correlation between chronic microbial infection and microglial activation. This review outlines three potential inter-organ communication routes for infectious microbes in microglial activation—the gut-brain axis, the lung-brain axis, and the nose-brain axis—thus emphasizing the interaction between microglia and inflammation and proving that neuroinflammation is a significant factor in pathogen-induced neurodegenerative diseases. Collectively, we propose that therapies which target relevant inflammatory mediators, along with antibiotics that target neuropathogens, could potentially alleviate neuroinflammation and treat neurodegenerative diseases.

Conflict of interest

All authors declare no conflicts of interest in this paper.

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