Dietary,environmental or genetic changes contribute to the development of several metabolic and neurological diseases.Extensive research efforts have been directed towards examining how these fac-tors modulate gut bac...Dietary,environmental or genetic changes contribute to the development of several metabolic and neurological diseases.Extensive research efforts have been directed towards examining how these fac-tors modulate gut bacterial composition.However,the mechanisms by which changes in gut bacterial diversity affect host function are not completely defined.Intestinal barrier dysfunction is being increasingly recognized as an early or initiating step in communicating bacterial diversity-dependent changes to the host.Here,we review the functional composition of the intestinal barrier and describe the consequences of the breach of this barrier.The functional layers of the intestinal barrier provide an initial defense and prevent the infiltration of bacteria or bacterial products from the gut lumen to the underlying lamina propria.Mesenteric lymph nodes subsequently act as the first firewall where dendritic cells from the lamina propria transport the infiltrated bacteria or bacterial products during the early stages of barrier dysfunction.When overwhelmed,the liver functions as the second firewall to detoxify bacterial endotoxins,such as lipopolysaccharide(LPS),and limit systemic involvement.Continuous translocation of LPS from the leaky gut to the liver results in liver damage or dysfunction that leads to the development of type 2 diabetes,atherosclerosis,heart disease,heart failure and also neurological dis-eases,such as Alzheimer’s and Parkinson’s disease.Thus,targeted restoration of intestinal barrier function represents a novel strategy for the attenuation of multiple diseases.展开更多
文摘Dietary,environmental or genetic changes contribute to the development of several metabolic and neurological diseases.Extensive research efforts have been directed towards examining how these fac-tors modulate gut bacterial composition.However,the mechanisms by which changes in gut bacterial diversity affect host function are not completely defined.Intestinal barrier dysfunction is being increasingly recognized as an early or initiating step in communicating bacterial diversity-dependent changes to the host.Here,we review the functional composition of the intestinal barrier and describe the consequences of the breach of this barrier.The functional layers of the intestinal barrier provide an initial defense and prevent the infiltration of bacteria or bacterial products from the gut lumen to the underlying lamina propria.Mesenteric lymph nodes subsequently act as the first firewall where dendritic cells from the lamina propria transport the infiltrated bacteria or bacterial products during the early stages of barrier dysfunction.When overwhelmed,the liver functions as the second firewall to detoxify bacterial endotoxins,such as lipopolysaccharide(LPS),and limit systemic involvement.Continuous translocation of LPS from the leaky gut to the liver results in liver damage or dysfunction that leads to the development of type 2 diabetes,atherosclerosis,heart disease,heart failure and also neurological dis-eases,such as Alzheimer’s and Parkinson’s disease.Thus,targeted restoration of intestinal barrier function represents a novel strategy for the attenuation of multiple diseases.
