Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.
Department of Microbiome Science, Max Planck Institute for Developmental Biology, Tübingen, Germany.
Nat Commun. 2019 Dec 11;10(1):5650. doi: 10.1038/s41467-019-13538-y.
Alterations in gut microbiota composition are associated with metabolic syndrome and chronic inflammatory diseases such as inflammatory bowel disease. One feature of inflammation-associated gut microbiotas is enrichment of motile bacteria, which can facilitate microbiota encroachment into the mucosa and activate pro-inflammatory gene expression. Here, we set out to investigate whether elicitation of mucosal anti-flagellin antibodies by direct administration of purified flagellin might serve as a general vaccine against subsequent development of chronic gut inflammation. We show, in mice, that repeated injection of flagellin elicits increases in fecal anti-flagellin IgA and alterations in microbiota composition, reduces fecal flagellin concentration, prevents microbiota encroachment, protects against IL-10 deficiency-induced colitis, and ameliorates diet-induced obesity. Flagellin's impact on the microbiota is B-lymphocyte dependent and, in humans, obese subjects exhibit increased levels of fecal flagellin and reduced levels of fecal flagellin-specific IgA, relative to normal weight subjects. Thus, administration of flagellin, and perhaps other pathobiont antigens, may confer some protection against chronic inflammatory diseases.
肠道微生物组成的改变与代谢综合征和慢性炎症性疾病（如炎症性肠病）有关。与炎症相关的肠道微生物组的一个特征是运动细菌的富集，这可以促进微生物侵入粘膜并激活促炎基因表达。在这里，我们着手研究直接给予纯化的鞭毛蛋白是否可以引发粘膜抗鞭毛蛋白抗体，从而作为预防慢性肠道炎症发展的通用疫苗。我们在小鼠中表明，鞭毛蛋白的重复注射会引起粪便抗鞭毛蛋白 IgA 的增加和微生物组成的改变，降低粪便鞭毛蛋白浓度，防止微生物侵入，预防 IL-10 缺乏诱导的结肠炎，并改善饮食诱导的肥胖。鞭毛蛋白对微生物群的影响依赖于 B 淋巴细胞，并且在人类中，与正常体重受试者相比，肥胖受试者的粪便鞭毛蛋白水平升高，粪便鞭毛蛋白特异性 IgA 水平降低。因此，鞭毛蛋白（和其他可能的条件致病菌抗原）的给药可能为预防慢性炎症性疾病提供一定的保护。
