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

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          Abstract

          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 using artificial intelligence, then revised and fact-checked by the author.

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          Most cited references43

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          Link between gut-microbiome derived metabolite and shared gene-effects with hepatic steatosis and fibrosis in NAFLD

          Previous studies have shown that gut-microbiome is associated with nonalcoholic fatty liver disease (NAFLD). We aimed to examine if serum metabolites especially those derived from the gut-microbiome have a shared gene-effect with hepatic steatosis and fibrosis. This is a cross-sectional analysis of a prospective discovery cohort including 156 well-characterized Twins and Families with untargeted metabolome profiling assessment. Hepatic steatosis was assessed using magnetic-resonance-imaging proton-density-fat-fraction (MRI-PDFF) and fibrosis using MR-elastography (MRE). A twin additive genetics and unique environment effects (AE) model was used to estimate the shared gene-effect between metabolites and hepatic steatosis and fibrosis. The findings were validated in an independent prospective validation cohort of 156 participants with biopsy-proven NAFLD including shotgun metagenomics sequencing assessment in a subgroup of the cohort. In the discovery cohort, 56 metabolites including 6 microbial metabolites had a significant shared gene-effect with both hepatic steatosis and fibrosis after adjustment for age, sex and ethnicity. In the validation cohort 6 metabolites were associated with advanced fibrosis. Among them, only one microbial metabolite, 3-(4-hydroxyphenyl)lactate, remained consistent and statistically significantly associated with liver fibrosis in the discovery and validation cohort (fold-change of higher-MRE versus lower-MRE: 1.78, p<0.001 and of advanced versus no advanced fibrosis: 1.26, p=0.037, respectively). The share genetic determination of 3-(4-hydroxyphenyl)lactate with hepatic steatosis was R G : 0.57, 95%CI: 0.27–0.80, p<0.001 and with fibrosis was R G : 0.54, 95%CI: 0.036–1, p=0.036. Pathway reconstruction linked 3-(4-hydroxyphenyl)lactate to several human gut-microbiome species. In the validation cohort, 3-(4-hydroxyphenyl)lactate was significantly correlated with the abundance of several gut-microbiome species, belonging only to Firmicutes, Bacteroidetes and Proteobacteria phyla, previously reported as associated with advanced fibrosis. Conclusion: This proof of concept study provides evidence of a link between the gut-microbiome and 3-(4-hydroxyphenyl)lactate that shares gene-effect with hepatic steatosis and fibrosis.
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            The oncogenic and clinical implications of lactate induced immunosuppression in the tumour microenvironment

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              Changes to the gut microbiota induced by losartan contributes to its antihypertensive effects

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                Author and article information

                Contributors
                zhoupk@bmi.ac.cn
                huangruixue@csu.edu.cn
                Journal
                Exp Mol Med
                Exp Mol Med
                Experimental & Molecular Medicine
                Nature Publishing Group UK (London )
                1226-3613
                2092-6413
                1 December 2023
                1 December 2023
                December 2023
                : 55
                : 12
                : 2596-2607
                Affiliations
                [1 ]Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, ( https://ror.org/00f1zfq44) Changsha, Hunan Province 410078 China
                [2 ]GRID grid.73113.37, ISNI 0000 0004 0369 1660, Translational Medicine Research Center, , Naval Medical University, ; 800, Xiangyin Road, 200433 Shanghai, People’s Republic of China
                [3 ]GRID grid.216417.7, ISNI 0000 0001 0379 7164, Department of Otolaryngology Head and Neck Surgery, The Second Xiangya Hospital, , Central South University, ; Changsha, 410011 Hunan Province China
                [4 ]Department of Systems Biology and Engineering, Silesian University of Technology, Institute of Automatic Control, ( https://ror.org/02dyjk442) Akademicka 16, Gliwice, 44-100 Poland
                [5 ]Biotechnology Centre, Silesian University of Technology, ( https://ror.org/02dyjk442) Krzywoustego 8, Gliwice, 44-100 Poland
                [6 ]GRID grid.506261.6, ISNI 0000 0001 0706 7839, Department of Radiation Biology, Beijing Key Laboratory for Radiobiology, , Beijing Institute of Radiation Medicine, ; Beijing, 100850 China
                Author information
                http://orcid.org/0000-0001-9280-6551
                Article
                1129
                10.1038/s12276-023-01129-3
                10766629
                38036735
                b07c2594-a734-4751-9050-ba37d06cb881
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 17 July 2023
                : 24 September 2023
                : 25 September 2023
                Categories
                Article
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                © Korean Society for Biochemical and Molecular Biology 2023

                Molecular medicine
                chemokines,cancer prevention
                Molecular medicine
                chemokines, cancer prevention

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