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bioRxiv2026

Porphyromonas gingivalis promotes lipid droplet-mediated microglial dysfunction

Growing evidence supports a strong association between periodontitis and Alzheimers disease (AD), yet the mechanisms linking these conditions remain poorly defined. In neurodegenerative disorders, including AD, microglia are often characterized by increased lipid droplet (LD) accumulation, heightened activation, and impaired function. In this study, we examined whether Porphyromonas gingivalis (Pg), a keystone periodontal pathogen, promotes LD accumulation in microglia and disrupts their function. We found that Pg infection induces robust LD accumulation in BV2 microglial cells and in microglia from Pg-infected App KI mice. This Pg-driven LD buildup was closely associated with elevated reactive oxygen species (ROS) production, impaired phagocytic ability, and altered activation. Notably, pharmacological inhibition of LD with a triglyceride synthesis inhibitor effectively reversed Pg-induced LD accumulation, mitigated ROS production, and restored phagocytic function, thus underscoring the critical role of lipid metabolism in regulating microglial function. These findings support a model in which, in the context of periodontitis, systemic dissemination of periodontal pathogens promotes LD accumulation in microglia, and this metabolic alteration exacerbates microglia dysfunction via a self-reinforcing cycle of excessive oxidative stress and impaired phagocytosis, potentially accelerating AD progression.

neuroscience↗

bioRxiv2023

Characterizing the microbial metagenome of calcareous stromatolite formations in the San Felipe Creek in Anza Borrego Desert

Here we describe the metagenome composition, community functional annotation, and diversity of prokaryotic microbial species derived from calcareous stromatolite formations discovered in the dry stream bed of the open-canopy, ephemeral San Felipe Creek in the Anza Borrego Desert. In this environment, resident microbes must be able to adapt to the harsh conditions of extreme heat, high UV light, desiccation and fluctuating solubilization/precipitation and hydration/evaporation. Metagenomic analysis revealed a community capable of carrying out complete nitrogen fixation and assimilatory nitrate reduction, forming biofilms and quorum sensing, and potentially forming thick-walled akinetes as desiccation-resistant stages. Nitrogen cycling is likely to play a fundamental role in mediating both the structure of the stromatolite microbial community and the mineral precipitation/dissolution. The viruses present in the stromatolites, particularly Nodularia and Mycobacterium phages are also likely to impact community population dynamics and activity. Stromatolite community members possess different morphological and physiological strategies to cope with desiccation stress. Metagenomic signatures were found for scytonemin, carotenoids, synthesis of potential microsporine-like amino acids; genes involved in microalgal desiccation tolerance, including those encoding aquaporins, chaperones, antioxidants; and enzymes responsible for the synthesis of trehalose, sucrose, and polyamines. The stromatolite ecosystem provides a diverse array of microniches where different functional guilds can develop complex metabolite exchange with the substrate supporting their life in extreme conditions. Metagenome analyses revealed several genes that might enable a specialized and unique group of endolithic cyanobacteria including Chroococcidiopsis, Hyella, Myxosarcina, and Pleurocapsa to derive metals and important nutrients from rocks, being potentially destructive for the calcareous formations. Our study revealed environmental adaptations of freshwater microbial communities in desert stream stromatolites which may provide valuable insights into Precambrian paleoenvironments, which are little known.

genomics↗