预防性口服白藜芦醇可缓解与人类肠道微生物群相关的 IL-10-/- 小鼠的急性弯曲杆菌病。

European journal of microbiology & immunology Pub Date : 2023-12-15 Print Date: 2023-12-21 DOI:10.1556/1886.2023.00042
Markus M Heimesaat, Niklas Schabbel, Luis Q Langfeld, Nizar W Shayya, Soraya Mousavi, Stefan Bereswill
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摘要

在全球范围内,人类感染食源性人畜共患肠道病原体空肠弯曲菌的人数不断增加。由于多重耐药菌株进一步增多,因此需要采取不依赖抗生素的措施来抗击弯曲杆菌病。多酚类化合物白藜芦醇具有抗微生物和抗炎特性,是一种很有前景的候选分子。在我们目前进行的安慰剂对照干预试验中,合成白藜芦醇被用于口服空肠病菌感染前一周开始的人类肠道微生物相关(hma)IL-10-/-小鼠。我们的分析表明,在感染后第 6 天,白藜芦醇预防剂不会干扰空肠杆菌在小鼠胃肠道内的繁殖,但会减轻弯曲杆菌病的临床症状,并减少结肠上皮细胞凋亡。此外,口服白藜芦醇可抑制空肠弯曲杆菌诱导的结肠 T 细胞和 B 细胞反应以及肠道促炎介质(包括一氧化氮、IL-6、TNF-α 和 IFN-γ)的分泌,使其降至基础水平。此外,在 hma IL-10-/- 小鼠患弯曲杆菌病期间,施用白藜芦醇不会导致结肠共生微生物群组成发生显著变化。总之,我们的安慰剂对照干预研究提供了证据,证明预防性口服白藜芦醇是缓解急性弯曲杆菌病的一种很有前景的策略,从而降低了感染后自身免疫后遗症的风险。
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Prophylactic oral application of resveratrol to alleviate acute campylobacteriosis in human gut microbiota associated IL-10-/- mice.

Human infections with the food-borne zoonotic enteropathogen Campylobacter jejuni are increasing globally. Since multi-drug resistant bacterial strains are further on the rise, antibiotic-independent measures are needed to fight campylobacteriosis. Given its anti-microbial and anti-inflammatory properties the polyphenolic compound resveratrol constitutes such a promising candidate molecule. In our present placebo-controlled intervention trial, synthetic resveratrol was applied perorally to human gut microbiota-associated (hma) IL-10-/- mice starting a week before oral C. jejuni infection. Our analyses revealed that the resveratrol prophylaxis did not interfere with the establishment of C. jejuni within the murine gastrointestinal tract on day 6 post-infection, but alleviated clinical signs of campylobacteriosis and resulted in less distinct colonic epithelial apoptosis. Furthermore, oral resveratrol dampened C. jejuni-induced colonic T and B cell responses as well as intestinal secretion of pro-inflammatory mediators including nitric oxide, IL-6, TNF-α, and IFN-γ to basal levels. Moreover, resveratrol application was not accompanied by significant shifts in the colonic commensal microbiota composition during campylobacteriosis in hma IL-10-/- mice. In conclusion, our placebo-controlled intervention study provides evidence that prophylactic oral application of resveratrol constitutes a promising strategy to alleviate acute campylobacteriosis and in consequence, to reduce the risk for post-infectious autoimmune sequelae.

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