The human gut microbiota is a complex ecosystem involved in the metabolism, immunity, and health of the host. The microbiome plays a key role in the development of the host's innate and adaptive immune system, while the immune system orchestrates the maintenance of host-microbe symbiosis. Lung diseases are usually accompanied by dysbiosis of the intestinal flora and an immune-inflammatory response. The intestinal flora and its metabolites are directly or indirectly involved in the immune regulation of the host in lung disease. However, the exact mechanism of action of the gut-lung axis crosstalk remains unclear. This review is aimed to summarize the latest advances in gut microbiota and their metabolites in typical lung diseases, such as pulmonary hypertension, COPD, and lung cancer. Especially COVID-19, a problem troubling the world, is also discussed in it. Moreover, it is concentrated on the action mechanisms between the identified gut microbiota or their metabolites and the specific lung diseases, and on the link among the gut microbiota, its metabolites, and immune regulation, which could be used as a breakthrough to find new mechanisms and targets for some diseases without specific therapeutic drugs in clinic. It is also discussed a new therapeutic tool "drug-bacterial interaction" and the potential of therapeutic applications in clinic. This review would provide a clear direction for future research on gut microbiota and lung diseases, and propose a new therapeutic strategy targeting "drug-bacterial interaction" in clinic.

Objectives: SIRT1 is an antioxidative factor, but its mechanism in methamphetamine (MA)‐induced lung injury remains unclear. The purpose of this study is to determine whether MA can disrupt the integrity of alveolar epithelial barrier, whether SIRT1 is involved in MA‐induced chronic lung injury and whether Resveratrol (Res) can protect the integrity of alveolar epithelial cells by regulating ROS to activate SIRT1/PTEN/p‐Akt pathway.Materials and methods: The rats were randomly divided into control group and MA group. Extracted lungs were detected by Western blot, HE staining and immunohistochemistry. The alveolar epithelial cells were treated with MA or/and Res, following by Western blot, LDH leakage assay and flow cytometry. MOE is used for bio‐informatics prediction.Results: Chronic exposure to MA can cause slower growth ratio of weight, increased RVI and induced lung injury including the reduced number of alveolar sacs and the thickened alveolar walls. MA‐induced apoptosis was associated with SIRT1‐related oxidative stress. Res suppressed ROS levels, activated SIRT1, negatively regulated PTEN, phosphorylated Akt, reduced LDH leakage, increased the expression of ZO‐1 and E‐cadherin and inhibited the apoptosis of alveolar epithelial cells to attenuate MA‐induced higher permeability of alveolar epithelium.Conclusions: MA disrupted the integrity of alveolar epithelial barrier. Res inhibited oxidative stress and reversed MA‐induced higher permeability and apoptosis of alveolar epithelium by the activation of SIRT1/PTEN/p‐Akt pathway.

Methamphetamine is a derivative of amphetamines, a highly addictive central stimulant with multiple systemic toxicity including the brain, heart, liver, lung, and spleen. It has adverse effects such as apoptosis and breakdown of the blood-brain barrier. Methamphetamine is a fatal and toxic chemical substance, and its lethal mechanism has been widely studied in recent years. The possible mechanism is that methamphetamine can cause cardiotoxicity and neurotoxicity mainly by inducing oxidative stress so as to generate heat, eliminate people’s hunger and thirst, and maintain a state of excitement so that people can continue to exercise. According to many research, there is no doubt that methamphetamine triggers neurotoxicity by inducing reactive oxygen species (ROS) production and redox imbalance. This review summarized the mechanisms of methamphetamine-induced neurotoxicity including apoptosis and blood-brain barrier breakdown through oxidative stress and analyzed several possible antioxidative mechanisms of tert-butylhydroquinone (TBHQ) which is a kind of food additive with antioxidative effects. As a nuclear factor E2-related factor 2 (Nrf2) agonist, TBHQ may inhibit neurotoxicity caused by oxidative stress through the following three mechanisms: the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system, the astrocytes activation, and the glutathione pathway. The mechanism about methamphetamine’s toxic effects and its antioxidative therapeutic drugs would become a research hotspot in this field and has very important research significance.

Methamphetamine (METH) is one of the psychostimulants most widely abused in the world. METH abuse can lead to severe neurotoxicity. The blood-brain barrier (BBB) is a natural barrier separating the central nervous system (CNS) from the peripheral blood circulation, which can limit or regulate the exchange of toxic substances, molecules, ions, etc., to maintain the homeostasis of CNS. Long-term or high dose abuse of METH can cause structural or functional abnormalities of the BBB and increase the risk of neurodegenerative diseases. In this review, we discussed the mechanisms of METH-induced BBB dysfunction, summarized the risk factors that could exacerbate METH-induced BBB dysfunction, and introduced some potential therapeutic agents. It would provide an important basis and direction for the prevention and treatment of BBB dysfunction induced by METH.