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Effect of chronic cold stress on gut microbial diversity, intestinal inflammation and pyroptosis in mice

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Abstract

Hypothermia is an essential environmental factor in gastrointestinal diseases, but the main molecular mechanisms of pathogenesis remain unclear. The current study sought to better understand how chronic cold stress affects gut damage and its underlying mechanisms. In this work, to establish chronic cold stress (CS)-induced intestinal injury model, mice were subjected to continuous cold exposure (4 °C) for 3 h per day for 3 weeks. Our results indicated that CS led to gut injury via inducing changes of heat shock proteins 70 (HSP70) and apoptosis-related (caspases-3, Bax and Bcl-2) proteins; enhancing expression of intestinal tight-related (ZO-1 and occludin) proteins; promoting releases of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), high mobility group box 1 (HMGB1), interleukin1β (IL-1β), IL-18 and IL-6 inflammatory mediators in the ileum; and altering gut microbial diversity. Furthermore, persistent cold exposure resulted in the cleavage of pyroptosis-related Gasdermin D (GSDMD) protein by regulating the NLRP3/ASC/caspase-1 and caspase-11 pathway, and activation of toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)-mediated nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, which are strongly associated with changes in gut microbiota diversity. Taken together, these investigations provide new insights into the increased risk of intestinal disorders at extremely low temperatures and establish a theoretical foundation for the advancement of novel pharmaceutical interventions targeting cold-related ailments.

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Data availability

The original data analyzed during the current study are available from the corresponding author upon reasonable request.

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Funding

This work was supported by the National Natural Science Foundation of China (grant no. 32202862), the General Financial from the Natural Science Foundation of Heilongjiang Province of China (grant no. YQ2021C028), the General Project of National Natural Science Foundation of China (grant no. 31972637), Heilongjiang Bayi Agricultural University Support Program for San Heng San Zong (grant no. ZRCQC202305).

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  1. Hongming Lv and Shijie Xia equally contributed to this work.

Authors and Affiliations

  1. Key Laboratory of Bovine Disease Control in Northeast China, Ministry of Agriculture and Rural Affairs; Heilongjiang Provincial Key Laboratory of Prevention and Control of Bovine Diseases; College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, 163319, China

    Hongming Lv, Shijie Xia, Yuxi He, Chunyu Qiao, Jiahe Liu, Jingru Guo & Shize Li

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Contributions

This manuscript was accomplished by Hongming Lv, Shijie Xia, Yuxi He, Chunyu Qiao, Jiahe Liu, Jingru Guo and Shize Li. Moreover, HM L and SJ X wrote original draft and performed the experiments; YX H, JH L, and CY Q, performed methodology and software; JR G contributed to supervise the experiments and paper; SZ L contributed to funding acquisition and review and editing the paper. All authors read and approved the final manuscript.

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Correspondence to Jingru Guo or Shize Li.

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This study has been approved by the Institutional Animal Care and Use Committee of Heilongjiang Bayi Agricultural University.

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Lv, H., Xia, S., He, Y. et al. Effect of chronic cold stress on gut microbial diversity, intestinal inflammation and pyroptosis in mice. J Physiol Biochem (2024). https://doi.org/10.1007/s13105-024-01019-w

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