Fermented Wheat Germ Globulin Improves Lung Inflammation In Smoke-exposed Mice

Background There are approximately 350 million smokers in China,the highest number in the world,and a number of studies have shown that smokers are more than twice as likely to develop lung diseases such as pneumonia and chronic obstructive pulmonary disease as the general population.Glucocorticoids and other drugs have been used clinically as the main treatment for chronic lung diseases,but the side effects are obvious and resistance to long-term drug treatment has developed.In recent years,there has been increasing research into the use of functional foods with modulating and dietary properties to intervene in chronic lung diseases such as lung infections,which have the advantage of being safer than drug therapy.Wheat germ globulin has been shown to have biological activities such as antioxidant and immune boosting properties,and the functional activity of wheat germ fermented with probiotics has been further improved,but studies on the use of fermented wheat germ globulin to intervene in smoke exposed lung injury have not been reported.Objective To investigate the protective effect of fermented wheat germ globulin on the physiological and biochemical properties of smoke exposure-induced lung inflammation in mice,and to elucidate its regulatory mechanism on lung inflammatory cytokines.Methods Firstly,the structure and in vitro activity of fermented wheat germ globulin were characterized by free amino acids,secondary structure,free radical scavenging rate and microstructure observation,and secondly,the enzymatic digestion of fermented wheat germ globulin in the gastrointestinal tract and the in vivo release of related functional factors were investigated by simulated digestion experiments.A model of lung injury caused by smoke exposure was established in Kunming mice,and the mechanism of fermented wheat germ globulin in improving lung inflammation and cytokine regulation in mice exposed to smoke was investigated at multiple levels,including physiological and biochemical aspects,oxidative stress and regulation of inflammatory factors.This study can provide a theoretical basis for the development of fermented wheat germ globulin to improve lung inflammation in smoke-exposed mice.Results (1)The fermented wheat germ globulins had significantly higher free amino acid content,significantly more irregular curl and showed a sparse and porous microstructure.The fermented wheat germ globulins were significantly stronger than wheat germ globulins in scavenging DPPH radicals and hydroxyl radicals.The results of comparative proteomic analysis indicated that the differential proteins of fermented wheat germ had important roles in the regulation of inflammation and oxidative stress.(2)The average particle size of fermented wheat germ globulin was degraded from 100 nm to 50-70 nm and 20-30 nm respectively after gastrointestinal digestion,and the relative molecular mass of undigested protein was stabilized around 15 k Da.A variety of functional amino acids were released in large quantities,and the content of aromatic and branched chain amino acids increased significantly.The DPPH free radical scavenging rate increased after digestion was completed.(3)The fermented wheat germ globulin significantly improved the organ damage caused by smoke exposure in mice,and contributed to the recovery of the total antioxidant capacity of liver and lung in the model mice,and reduced the oxidative stress damage caused by smoke exposure.The alveolar swelling,alveolar wall disruption,infiltration of inflammatory cells and aggregation of inflammatory cells in lung tissue were significantly reduced in the fermented wheat germ globulin-treated mice.Fermented wheat germ globulin intervention significantly down-regulated the expression of IL-6,TNF-α and IL-1β,and significantly down-regulated the expression of TLR4,My D88 and NF-κBp65 in the NF-κB signaling pathway at the transcriptional level.(4)Fermented wheat germ globulin was able to increase intestinal microbial diversity and increase the B/F value at the gate level;the dominant bacteria in the fermented wheat germ globulin group at the gate level were Frmieutes,Bactergrdota,Actinobacterota,Patescibactera,Proteobacteria,and Bactergrdota increased.Comparative sample analysis showed that the model group was significantly different from the blank control and intervention groups;differential genus analysis revealed that fermented wheat germ globulin significantly reduced the abundance of pathogenic bacteria such as Aerococcus,Corynebacterium,and Staphylococcus(p < 0.05);clinical factor association analysis showed that intestinal flora diversity was associated with in vivo The results of the clinical factor association analysis showed a significant correlation between intestinal flora diversity and the regulation of inflammation and oxidative stress in vivo.Conclusions Fermented wheat germ can reduce oxidative stress in liver and lung,down-regulate the expression of inflammatory cytokines,and inhibit the expression of TLR4,My D88 and NF-κBp65 at the transcriptional level to interfere with smoke exposure-induced lung injury,revealing the mechanism by which fermented wheat germ globulin can reduce lung inflammation in smoke exposed mice by inhibiting NF-κB signaling pathway.Based on the "intestine-lung axis" theory,we further revealed that fermented wheat germ globulin could reduce lung inflammation in smoke-exposed mice by improving intestinal microecology.This study provides a theoretical basis for the development of fermented wheat germ globulin functional foods to reduce lung damage caused by smoke exposure.