Du Ke, Foote Minnja S, Mousavi Soraya, Buczkowski Agnes, Schmidt Sebastian, Bereswill Stefan, Heimesaat Markus M
Gastrointestinal Microbiology Research Group, Institute of Microbiology, Infectious Diseases and Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, 12203 Berlin, Germany.
Hofmann & Sommer GmbH und Co., KG, Büro Berlin, 12489 Berlin, Germany.
Microorganisms. 2022 Sep 30;10(10):1953. doi: 10.3390/microorganisms10101953.
Given that human infections are rising globally and antibiotic treatment is not recommended, infected patients would substantially benefit from alternative therapeutic strategies. Short-chain fatty acids such as butyrate are known for their health benefits, including anti-microbial and anti-inflammatory effects. This prompted us to investigate potential disease-alleviating properties of butyrate treatment during acute murine -induced enterocolitis. Therefore, following gut microbiota depletion IL-10 mice were challenged with 10 viable cells by oral gavage and treated with butyrate via the drinking water (22 g/L) starting on day 2 post-infection. As early as day 3 post-infection, butyrate reduced diarrheal severity and frequency in treated mice, whereas on day 6 post-infection, gastrointestinal burdens and the overall clinical outcomes were comparable in butyrate- and placebo-treated cohorts. Most importantly, butyrate treatment dampened intestinal pro-inflammatory immune responses given lower colonic numbers of apoptotic cells and neutrophils, less distinct TNF-α secretion in mesenteric lymph nodes and lower IL-6 and MCP-1 concentrations in the ileum. In conclusion, results of our preclinical intervention study provide evidence that butyrate represents a promising candidate molecule for the treatment of acute campylobacteriosis.
鉴于全球范围内人类感染病例不断增加，且不建议使用抗生素治疗，感染患者将从替代治疗策略中大幅受益。短链脂肪酸如丁酸因其对健康有益而闻名，包括抗菌和抗炎作用。这促使我们研究在急性小鼠诱导的小肠结肠炎期间丁酸治疗的潜在疾病缓解特性。因此，在肠道微生物群耗竭后，通过口服灌胃用10个活细胞对IL-10小鼠进行攻击，并在感染后第2天开始通过饮用水（22 g/L）用丁酸进行治疗。早在感染后第3天，丁酸就降低了治疗小鼠的腹泻严重程度和频率，而在感染后第6天，丁酸治疗组和安慰剂治疗组的胃肠道负担和总体临床结果相当。最重要的是，丁酸治疗抑制了肠道促炎免疫反应，表现为结肠中凋亡细胞和中性粒细胞数量减少，肠系膜淋巴结中TNF-α分泌不那么明显，回肠中IL-6和MCP-1浓度降低。总之，我们的临床前干预研究结果提供了证据，表明丁酸是治疗急性弯曲菌病的一个有前景的候选分子。
