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Abstract：
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, in vivo 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.
摘要：
肠道微生物群与各种疾病的发生和发展有关；然而，潜在的机制仍然难以捉摸,并且缺乏有效的治疗策略.在这项研究中,我们研究了肠道菌群在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作为治疗干预的潜力.直肠内给药TNBS诱导的小鼠结肠炎，同时肾损害。有趣的是,当TNBS腹膜内给药时，这种作用是不存在的，表明肠道微生物群的潜在作用。用抗生素消耗肠道细菌可显着减轻TNBS诱导的炎症的严重程度，氧化损伤，以及结肠和肾脏的组织损伤。使用培养的结肠上皮细胞和骨髓巨噬细胞的机制研究揭示了TNBS诱导的细胞氧化，炎症和损伤，通过细菌成分LPS扩增，并通过硫醇抗氧化剂减轻。重要的是,体内施用富含巯基的乳清蛋白完全预防了TNBS诱导的结肠和肾损伤。我们的研究结果表明，肠道细菌显著有助于结肠炎的开始和进展以及相关的肾损伤，可能通过涉及LPS诱导的氧化细胞损伤夸大的机制。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.
