Another study reported that gut dysbiosis including an aging-associated decrease in beneficial commensal bacteria such as Akkermansia muciniphila can lead to insulin resistance, which was evidenced by the findings that the loss of A. muciniphila and its product butyrate caused intestinal integrity disruption and endotoxin leakage, thereby activating CCR2+ monocytes and in turn triggering 4-1BB receptor signaling of innate B1a cells, resulting in impaired insulin signaling [227]. Here, INS is linked to Insulin resistance.