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, Hangzhou 310003, China.
Nutrients. 2023 Oct 18;15(20):4427. doi: 10.3390/nu15204427.
The ketogenic diet (KD) has emerged as a popular weight-loss regimen in recent years. However, it has been confirmed to elicit a mild inflammatory response in the intestinal epithelium and exacerbate various digestive disorders. The severity of acute pancreatitis (AP) is closely associated with the permeability of the intestinal epithelium and gut microbiota, yet the impact of KD on acute pancreatitis remains unclear. In this study, we induced acute pancreatitis using L-arginine in mice fed with KD. The consumption of KD resulted in an elevation of lipopolysaccharide-binding protein (LBP), accompanied by upregulated cytokines (IL-1a, IL-5, IL-12, MIP-1a, and Rantes) and dysfunction of the intestinal barrier both in control and AP groups. The bloom of and was observed as a specific profile of gut microbiota in KD-fed mice with AP, along with downregulation of carbohydrate metabolism and depletion of short-chain fatty acids (SCFAs). Antibiotic decontamination reduced the cytokine storm and tissue necrosis but did not significantly improve the integrity of the intestinal barrier in KD-fed mice with AP. The overgrowth of in feces and in colonic tissue appears to explain the limitation of antibiotic treatment to aggravate acute pancreatitis. Butyrate supplementation attenuated the depletion of SCFAs, promoted the intestinal barrier, and reduced the necrotic area in AP mice. The bloom of and the correlated increase in tryptophan metabolism explain the therapeutic potential of butyrate supplements for acute pancreatitis. In conclusion, our findings suggest that the ketogenic diet exacerbates acute pancreatitis through its impact on the gut microbiota and subsequent disruption of the intestinal barrier, while butyrate supplementation reverses this effect.
生酮饮食（KD）近年来已成为一种流行的减肥方法。然而，它已被证实会在肠道上皮引起轻度炎症反应，并加重各种消化疾病。急性胰腺炎（AP）的严重程度与肠道上皮的通透性和肠道微生物群密切相关，但 KD 对急性胰腺炎的影响尚不清楚。在本研究中，我们使用 L-精氨酸在 KD 喂养的小鼠中诱导急性胰腺炎。KD 的摄入导致脂多糖结合蛋白（LBP）升高，同时伴有细胞因子（IL-1a、IL-5、IL-12、MIP-1a 和 Rantes）上调和肠道屏障功能障碍，无论是在对照组还是 AP 组中都是如此。在 KD 喂养的 AP 小鼠中，观察到 和 的增加是肠道微生物群的特定特征，同时碳水化合物代谢减少和短链脂肪酸（SCFAs）耗竭。抗生素消毒减少了细胞因子风暴和组织坏死，但并没有显著改善 KD 喂养的 AP 小鼠的肠道屏障完整性。粪便中 和结肠组织中的 过度生长似乎解释了抗生素治疗加重急性胰腺炎的局限性。丁酸盐补充剂减轻了 SCFAs 的耗竭，促进了肠道屏障，并减少了 AP 小鼠的坏死区域。 和色氨酸代谢相关的增加解释了丁酸盐补充剂治疗急性胰腺炎的潜在治疗作用。总之，我们的研究结果表明，生酮饮食通过其对肠道微生物群的影响以及随后破坏肠道屏障来加重急性胰腺炎，而丁酸盐补充剂则可以逆转这种作用。
