Lactate exacerbates lung damage induced by nanomicroplastic through the gut microbiota–HIF1a/PTBP1 pathway

Exposure to nanomicroplastics (nano-MPs) can induce lung damage. The gut microbiota is a critical modulator of the gut–lung axis. However, the mechanisms underlying these interactions have not been elucidated. This study explored the role of lactate, a key metabolite of the microbiota, in the development of lung damage induced by nano-MPs (LDMP). After 28 days of exposure to nano-MPs (50–100 nm), mice mainly exhibited damage to the lungs and intestinal mucosa and dysbiosis of the gut microbiota. Lactate accumulation was observed in the lungs, intestines and serum and was strongly associated with the imbalance in lactic acid bacteria in the gut. Furthermore, no lactate accumulation was observed in germ-free mice, while the depletion of the gut microbiota using a cocktail of antibiotics produced similar results, suggesting that lactate accumulation in the lungs may have been due to changes in the gut microbiota components. Mechanistically, elevated lactate triggers activation of the HIF1a/PTBP1 pathway, exacerbating nano-MP-induced lung damage through modulation of the epithelial–mesenchymal transition (EMT). Conversely, mice with conditional knockout of Ptbp1 in the lungs ( Ptbp1 flfl ) and PTBP1 -knockout ( PTBP1 -KO) human bronchial epithelial (HBE) cells showed reversal of the effects of lactate through modulation of the HIF1a/PTBP1 signaling pathway. These findings indicate that lactate is a potential target for preventing and treating LDMP. Lactate: the hidden culprit in microplastic-induced lung damage This study examined the effects of nano-microplastics (minuscule particles of plastic found in the environment) on human health. The impact of these particles on the human respiratory and gastrointestinal (related to the stomach and intestines) systems remains unknown. The scientists found that exposure to nano-microplastics can concurrently harm the lungs and intestines in mice. This harm was connected to an increase in lactate (a type of acid produced by the body) levels in these organs, causing an imbalance in gut bacteria (microorganisms that live in the digestive tract). The study also noted that this harm could be transmitted via gut bacteria and that lactate intensified the lung harm induced by the nano-microplastics. This research deepens our understanding of the potential health risks of nano-microplastics exposure. The results could aid in devising strategies to prevent and manage resultant health problems. This summary was initially drafted u