Bidirectional relationship between the biofilm of Porphyromonas gingivalis and the amyloid-beta peptide

ABSTRACT Periodontitis and Porphyromonas gingivalis infections are significant risk factors for the onset of Alzheimer’s disease (AD). Despite the reliance of P. gingivalis on its biofilm for its survival and virulence, the impact of the extracellular matrix on AD’s neuropathological hallmarks has never been examined. In this study, we report a bidirectional relationship between the amyloid-beta (Aβ) peptide, which plays a central role in AD, and the biofilm of P. gingivalis . Using multiple fluorescent markers for biofilm components, we observed that Aβ 1-40 inhibited biofilm formation while Aβ 1-42 increased extracellular matrix production. Also, using thioflavin T staining and atomic force microscopy, we observed co-aggregation of the biofilm and monomeric Aβ 1-40 , resulting in faster aggregation and significant changes in aggregate structure. Our findings propose mechanistic explanations for the role of P. gingivalis as a risk factor for AD and offer potential mechanisms for microbial involvement in AD etiology. IMPORTANCE While the etiology of Alzheimer’s disease has been studied extensively for the past 50 years, its exact causes remain unknown. Our current understanding is that the accumulation of multiple genetic and environmental risk factors would lead to the onset of the disease. Porphyromonas gingivalis is a bacterium that produces biofilm and elicits periodontitis, a chronic infection of the gums that constitutes a risk factor for Alzheimer’s disease. While studies have looked at the effects of P. gingivalis in triggering Alzheimer’s symptoms in animal models, none have explored the impact of the biofilm, which is essential in this bacterium. Our study seeks to bridge that gap by demonstrating a bidirectional relationship between P. gingivalis biofilm and amyloid beta, one of the brain lesions involved in Alzheimer’s disease. By understanding the risk factors involved in Alzheimer’s disease and their impact, we aim to provide valuable insights on prevention and treatment.