State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine,79 Qingchun Rd., Hangzhou City 310003, China.
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine,79 Qingchun Rd., Hangzhou City 310003, China.
Life Sci. 2023 Dec 1;334:122188. doi: 10.1016/j.lfs.2023.122188. Epub 2023 Oct 20.
Butyrate, a short-chain fatty acid (SCFA), has demonstrated significant efficacy in preventing colitis-associated inflammation. Acute pancreatitis is an acute gastrointestinal disorder characterized by increased systemic inflammation, bacterial translocation, and disrupted intestinal barrier. However, the effects and mechanisms of butyrate in attenuating acute pancreatitis remain unclear. In this study, we established two mouse models of acute pancreatitis induced by cerulein (Cer) and taurocholate (TA), which were further exacerbated by a ketogenic diet (KD). The results suggested that butyrate supplementation effectively reduced mortality rates, systemic inflammation, and intestinal barrier disruption caused by Cer- and TA-induced acute pancreatitis in mice fed a KD. Furthermore, we observed a significant reduction in gut microbiota diversity as well as overgrowth of Lachnospirales and Erysipelotrichales along with depletion of SCFAs in mice fed a KD, and these alterations were reversed by butyrate supplement. To evaluate the role of microbiota and butyrate supplement, we conducted germ-depletion trials by antibiotics. The results showed that while systemic inflammation was attenuated in mice with TA-induced pancreatitis following antibiotic treatment, the reduction in mortality remained inconclusive (p = 0.055). Importantly, the key differential change between antibiotic treatment and butyrate supplementation was found to be related to intestinal barrier dysfunction and repairment. These results suggest that butyrate plays a central role in mitigating acute pancreatitis through amelioration of intestinal barrier dysfunction.
丁酸是一种短链脂肪酸 (SCFA)，已被证明在预防结肠炎相关炎症方面具有显著疗效。急性胰腺炎是一种以全身炎症增加、细菌易位和肠道屏障破坏为特征的急性胃肠道疾病。然而，丁酸在减轻急性胰腺炎方面的作用和机制尚不清楚。在这项研究中，我们建立了两种由鹅去氧胆酸（Cer）和牛磺胆酸钠（TA）诱导的急性胰腺炎小鼠模型，这些模型进一步被生酮饮食（KD）加剧。结果表明，丁酸补充剂可有效降低 KD 喂养的 Cer 和 TA 诱导的急性胰腺炎小鼠的死亡率、全身炎症和肠道屏障破坏。此外，我们观察到 KD 喂养的小鼠肠道微生物多样性显著降低，Lachnospirales 和 Erysipelotrichales 过度生长，SCFAs 耗竭，而丁酸补充可逆转这些改变。为了评估微生物群和丁酸补充的作用，我们通过抗生素进行了无菌试验。结果表明，尽管抗生素治疗可减轻 TA 诱导的胰腺炎小鼠的全身炎症，但死亡率的降低仍不确定（p=0.055）。重要的是，抗生素治疗和丁酸补充之间的关键差异变化被发现与肠道屏障功能障碍和修复有关。这些结果表明，丁酸通过改善肠道屏障功能在减轻急性胰腺炎方面发挥核心作用。
