Gut microbiota has been implicated in the initiation and progression of various diseases; however, the underlying mechanisms remain elusive and effective therapeutic strategies are scarce. In this study, we investigated the role and mechanisms of gut microbiota in TNBS-induced colitis and its associated kidney injury while evaluating the potential of dietary protein as a therapeutic intervention. The intrarectal administration of TNBS induced colitis in mice, concurrently with kidney damage. Interestingly, this effect was absent when TNBS was administered intraperitoneally, indicating a potential role of gut microbiota. Depletion of gut bacteria with antibiotics significantly attenuated the severity of TNBS-induced inflammation, oxidative damage, and tissue injury in the colon and kidneys. Mechanistic investigations using cultured colon epithelial cells and bone-marrow macrophages unveiled that TNBS induced cell oxidation, inflammation and injury, which was amplified by the bacterial component LPS and mitigated by thiol antioxidants. Importantly, administration of thiol-rich whey protein entirely prevented TNBS-induced colonic and kidney injury. Our findings suggest that gut bacteria significantly contribute to the initiation and progression of colitis and associated kidney injury, potentially through mechanisms involving LPS-induced exaggeration of oxidative cellular damage. Furthermore, our research highlights the potential of dietary thiol antioxidants as preventive and therapeutic interventions.

中文翻译：

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肠道细菌通过氧化应激加剧 TNBS 诱导的结肠炎和肾损伤

肠道微生物群与多种疾病的发生和进展有关。然而，潜在的机制仍然难以捉摸，有效的治疗策略也很少。在这项研究中，我们研究了肠道微生物群在 TNBS 诱导的结肠炎及其相关肾损伤中的作用和机制，同时评估了膳食蛋白质作为治疗干预的潜力。直肠内给予 TNBS 会引起小鼠结肠炎，同时还会损害肾脏。有趣的是，当 TNBS 腹腔注射时，这种效应不存在，这表明肠道微生物群的潜在作用。用抗生素消除肠道细菌可显着减轻 TNBS 诱导的结肠和肾脏炎症、氧化损伤和组织损伤的严重程度。使用培养的结肠上皮细胞和骨髓巨噬细胞进行的机制研究表明，TNBS 会诱导细胞氧化、炎症和损伤，这些现象会被细菌成分 LPS 放大，并被硫醇抗氧化剂减轻。重要的是，富含硫醇的乳清蛋白的施用完全防止了 TNBS 引起的结肠和肾脏损伤。我们的研究结果表明，肠道细菌可能通过涉及脂多糖诱导的氧化细胞损伤加剧的机制，显着促进结肠炎和相关肾损伤的发生和进展。此外，我们的研究强调了膳食硫醇抗氧化剂作为预防和治疗干预措施的潜力。