BACKGROUND The chaperone ClpB, a bacterial protein, is a conformational antigen-mimetic of α-melanocyte-stimulating hormone (α-MSH) implicated in body weight regulation in mice. We here investigated the potential associations of gut bacterial ClpB-like gene function with obesity status and gut microbiota in humans. RESULTS Gut microbiota ClpB KEGG function was negatively associated with body mass index, waist circumference, and total fat mass (DEXA). The relative abundance (RA) of several phyla and families directly associated with ClpB was decreased in subjects with obesity. Specifically, the RA of Rikenellaceae, Clostridiaceae and not assigned Firmicutes were lower in subjects with obesity and positively associated with gut bacterial ClpB-like gene function (not assigned Firmicutes (r = 0.405, FDR = 2.93 × 10-2), Rikenellaceae (r = 0.217, FDR = 0.031), and Clostridiaceae (r = 0.239, FDR = 0.017)). The gut bacterial ClpB-like gene function was also linked to specific plasma metabolites (hippuric acid and 3-indolepropionic acid) and fecal lupeol. The α-MSH-like epitope similar to that of Escherichia coli ClpB was also identified in some sequences of those bacterial families. After fecal transplantation from humans to mice, the families that more contributed to ClpB-like gene function in humans were also associated with ClpB-like gene function in mice after adjusting for the donor's body mass index (not assigned Firmicutes (r = 0.621, p = 0.003), Prevotellaceae (r = 0.725, p = 4.1 × 10-7), Rikenellaceae (r = 0.702, p = 3.9 × 10-4), and Ruminococcaceae (r = 0.526, p = 0.014)). Clostridiaceae (r = - 0.445, p = 0.038) and Prevotellaceae RA (r = - 0.479, p = 0.024) and were also negatively associated with weight gain in mice. The absolute abundance (AA) of Prevotellaceae in mice was also positively associated with the gut bacterial ClpB-like gene function in mice. DESeq2 identified species of Prevotellaceae, both negatively associated with mice' weight gain and positively with gut bacterial ClpB-like gene function. CONCLUSIONS In summary, gut bacterial ClpB-like gene function is associated with obesity status, a specific gut microbiota composition and a plasma metabolomics profile in humans that could be partially transplanted to mice. Video Abstract.

中文翻译：

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肠细菌ClpB样基因功能与体重下降和特征性微生物群谱有关。

背景技术伴侣蛋白ClpB是一种细菌性蛋白质，是一种α-黑素细胞刺激激素（α-MSH）的构象抗原模拟物，与小鼠的体重调节有关。我们在这里调查了人类肠道细菌ClpB样基因功能与肥胖状况和肠道菌群的潜在关联。结果肠道菌群ClpB KEGG功能与体重指数，腰围和总脂肪量（DEXA）呈负相关。肥胖受试者中与ClpB直接相关的几个门系和家族的相对丰度（RA）降低。具体来说，肥胖的受试者中，Rikenellaceae，Clostridiaceae和未分配的Firmicutes的RA较低，并且与肠道细菌ClpB样基因功能（未分配的Firmicutes（r = 0.405，FDR = 2.93×10-2），Rikenellaceae（r = 0.217，FDR = 0.031）和梭菌科（r = 0.239，FDR = 0.017））。肠细菌ClpB样基因功能也与特定的血浆代谢产物（马尿酸和3-吲哚丙酸）和粪便羽扇豆酚有关。在那些细菌家族的某些序列中也鉴定出类似于大肠杆菌ClpB的类似α-MSH的表位。从人类粪便移植到小鼠后，在调整了供体的体重指数后，对人类ClpB样基因功能贡献更大的家族也与小鼠ClpB样基因功能相关（未分配Firmicutes（r = 0.621，p = 0.003），原核科（r = 0.725，p = 4.1×10-7），Rikenellaceae（r = 0.702，p = 3.9×10-4）和Ruminococcaceae（r = 0.526，p = 0.014））。梭菌科（r =-0.445，p = 0.038）和原核科RA（r =-0.479，p = 0。024），也与小鼠体重增加呈负相关。小鼠原发藻科的绝对丰度（AA）也与小鼠肠道细菌ClpB样基因功能正相关。DESeq2鉴定了前鞭毛科物种，它们与小鼠的体重增加呈负相关，与肠道细菌的ClpB样基因功能呈正相关。结论总之，肠道细菌ClpB样基因的功能与肥胖状况，特定的肠道微生物群组成和人体血浆代谢组学特征有关，可以部分移植到小鼠中。录像摘要。与小鼠体重增加负相关，与肠道细菌ClpB样基因功能正相关。结论总之，肠道细菌ClpB样基因的功能与肥胖状况，特定的肠道菌群组成和人体血浆代谢组学特征有关，可以部分移植到小鼠中。录像摘要。与小鼠体重增加负相关，与肠道细菌ClpB样基因功能正相关。结论总之，肠道细菌ClpB样基因的功能与肥胖状况，特定的肠道菌群组成和人体血浆代谢组学特征有关，可以部分移植到小鼠中。录像摘要。