<b><i>Salivary pathobiont Klebsiella pneumoniae exacerbating </i></b><b><i>periodontitis-related intestinal dyshomeostasis</i></b><b><i>and accelerated metabolic syndrome</i></b>

The mutual relationship between periodontitis and diabetes has always been a heated topic, but regulatory targets have not been well elucidated. Severe periodontitis promotes opportunistic pathogen expansion in the oral cavity and facilitates ectopic colonization through the “oral-gut axis”. These oral-derived microorganisms ectopically colonize the intestine, are closely related to the progression of systemic diseases, and may therefore play the role of a bridge connection. Intestinal mucosal immunity and barrier functions play important roles in maintaining metabolic homeostasis. The dyshomeostasis of intestinal immunity mediated by the periodontitis microbiota is one of the potential ways for periodontitis to promote the progression of diabetes, and the microorganisms that play a key regulatory role are not yet clear. This study focuses on the role and related mechanisms of <i>Klebsiella pneumoniae</i> (<i>K. pneumoniae</i>) isolated from periodontitis salivary microbiota (Kp94) in metabolic regulation. The key targets of this oral-derived <i>K. pneumoniae</i> strain in regulating metabolic homeostasis in periodontitis were further explored. Kp94 inhibits intestinal mucosal immune function by downregulating ILC3/IL-22 signaling, promoting glucose metabolism disorders, and exacerbating metabolic syndrome and islet damage in diabetes. IL-22 treatment restored intestinal homeostasis and islet function damage induced by Kp94 and alleviated metabolic disorders in diabetes. Therefore, K. pneumoniae plays an important role in promoting diabetes in the presence of periodontitis by regulating intestinal ILC3/IL-22, and ILC3/IL-22 should be highlighted as a promising therapeutic target.