ArticleGut microbes
The intestinal microbial metabolite nicotinamide n-oxide prevents herpes simplex encephalitis via activating mitophagy in microglia.
Article in Gut microbes. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
- HSV-1 metabolic hijacking: Mechanisms to precision therapeutics.Virulence · 2026Review
- Mitophagy in pathogenesis and therapeutic implications for infection.Experimental & molecular medicine · 2026Review
- Mitophagy-mediated immune evasion: Shared strategies of pathogens.Redox biology · 2026Review
- Microglia and neuroinflammation: An in-depth analysis from functional diversity to disease mechanisms.Clinical and translational medicine · 2026Review
- NADThe Journal of general virology · 2026Review
- Novel Hsp90 inhibitor JD‑02 inhibits HSV‑1 infection via the Raf/MEK/ERK signaling pathway.International journal of molecular medicine · 2026Article
- Review
- Microbiota and Alzheimer's disease: mechanistic insights from a multi-organ perspective.Translational neurodegeneration · 2026Review
- The role of gut microbiota in neuropathic pain: insights into immune mechanisms.The journal of headache and pain · 2025Review
- A broadly neutralizing antibody confers cross-genus protection against alphaherpesviruses by inhibiting gB-mediated membrane fusion.Nature communications · 2025Article
- The Gut-Brain Axis in Alzheimer's Disease: Exploring Microbial Influences and Therapeutic Strategies.Molecular neurobiology · 2025Review
- Inhibition of mitophagy via the EIF2S1-ATF4-PRKN pathway contributes to viral encephalitis.Journal of advanced research · 2025Article
- Whole Blood Metabolomic Profiling of Mice with Tacrolimus-Induced Chronic Nephrotoxicity: NADAntioxidants (Basel, Switzerland) · 2025Article
- Article
- Histone deacetylases: the critical enzymes for microglial activation involved in neuropathic pain.Frontiers in pharmacology · 2025Review
- The role of probiotics, prebiotics, and postbiotics: cellular and molecular pathways activated on glial cells in Alzheimer's disease.Frontiers in neuroscience · 2025Review
- From a focal skin issue to a systemic disease: the multifaceted nature of cold sores, novel findings.Virusdisease · 2024Article
- The potential role of gut microbiota-derived metabolites as regulators of metabolic syndrome-associated mitochondrial and endolysosomal dysfunction in Alzheimer's disease.Experimental & molecular medicine · 2024Review
- Review
- Gut Metabolites Acting on the Gut-Brain Axis: Regulating the Functional State of Microglia.Aging and disease · 2024Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Herpes simplex encephalitis (HSE), a complication of herpes simplex virus type I (HSV-1) infection causes neurological disorder or even death in immunocompromised adults and newborns. However, the intrinsic factors controlling the HSE outcome remain unclear. Here, we show that HSE mice exhibit gut microbiota dysbiosis and altered metabolite configuration and tryptophan-nicotinamide metabolism. HSV-1 neurotropic infection activated microglia, with changed immune properties and cell numbers, to stimulate antiviral immune response and contribute substantially to HSE. In addition, depletion of gut microbiota by oral antibiotics (ABX)-treatment triggered the hyper-activation of microglia, which in turn enhanced inflammatory immune response, and cytokine production, resulting in aggregated viral burden and HSE pathology. Furthermore, exogenous administration of nicotinamide n-oxide (NAMO), an oxidative product of nicotinamide derived from gut microbiota, to ABX-treated or untreated HSE mice significantly diminished microglia-mediated proinflammatory response and limited HSV-1 infection in CNS. Mechanistic study revealed that HSV-1 activates microglia by increasing mitochondrial damage via defective mitophagy, whereas microbial metabolite NAMO restores NAD+-dependent mitophagy to inhibit microglia activation and HSE progression. NAMO also prevented neuronal cell death triggered by HSV-1 infection or microglia-mediated microenvironmental toxicity. Finally, we show that NAMO is mainly generated by neomycin-sensitive bacteria, especially
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.