Seok-Young Kim, Seung Yong Shin, Soo Jung Park, Jong Pil Im, Hyo Jong Kim, Kang-Moon Lee, Ji Won Kim, Sung-Ae Jung, Jun Lee, Sang-Bum Kang, Sung Jae Shin, Eun Sun Kim, You Sun Kim, Tae Oh Kim, Hyun-Soo Kim, Dong Il Park, Hyung Kil Kim, Eun Soo Kim, Young-Ho Kim, Dennis Teng, Jong-Hwa Kim, Wonyong Kim, Maham Saeed, Jung Min Moon, Kisung Kim, Chang Hwan Choi, Hyung-Kyoon Choi
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Clinical remission was assessed using the Mayo score. Metabolomic and lipidomic analyses were performed using gas chromatography mass spectrometry and nano electrospray ionization mass spectrometry, respectively. Orthogonal partial least squares discriminant analysis was performed to establish a remission prediction model.</p><p><strong>Results: </strong>Fecal metabolites in UC patients markedly differed from those in HC at baseline and were changed similarly to those in HC during treatment; however, lipid profiles did not show these patterns. After treatment, the fecal characteristics of remitters (RM) were closer to those of HC than to those of non-remitters (NRM). At 8 and 56 weeks, amino acid levels in RM were lower than those in NRM and similar to those in HC. After 56 weeks, levels of 3-hydroxybutyrate, lysine, and phenethylamine decreased, and dodecanoate level increased in RM similarly to those in HC. The prediction model of long-term remission in male patients based on lipid biomarkers showed a higher performance than clinical markers.</p><p><strong>Conclusion: </strong>Fecal metabolites in UC patients markedly differ from those in HC, and the levels in RM are changed similarly to those in HC after anti-TNF therapy. Moreover, 3-hydroxybutyrate, lysine, phenethylamine, and dodecanoate are suggested as potential therapeutic targets for UC. A prediction model of long-term remission based on lipid biomarkers may help implement personalized treatment.</p>","PeriodicalId":23022,"journal":{"name":"Therapeutic Advances in Gastroenterology","volume":"16 ","pages":"17562848231168199"},"PeriodicalIF":4.2000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/45/f9/10.1177_17562848231168199.PMC10161336.pdf","citationCount":"0","resultStr":"{\"title\":\"Changes in fecal metabolic and lipidomic features by anti-TNF treatment and prediction of clinical remission in patients with ulcerative colitis.\",\"authors\":\"Seok-Young Kim, Seung Yong Shin, Soo Jung Park, Jong Pil Im, Hyo Jong Kim, Kang-Moon Lee, Ji Won Kim, Sung-Ae Jung, Jun Lee, Sang-Bum Kang, Sung Jae Shin, Eun Sun Kim, You Sun Kim, Tae Oh Kim, Hyun-Soo Kim, Dong Il Park, Hyung Kil Kim, Eun Soo Kim, Young-Ho Kim, Dennis Teng, Jong-Hwa Kim, Wonyong Kim, Maham Saeed, Jung Min Moon, Kisung Kim, Chang Hwan Choi, Hyung-Kyoon Choi\",\"doi\":\"10.1177/17562848231168199\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Therapeutic targets for ulcerative colitis (UC) and prediction models of antitumor necrosis factor (TNF) therapy outcomes have not been fully reported.</p><p><strong>Objective: </strong>Investigate the characteristic metabolite and lipid profiles of fecal samples of UC patients before and after adalimumab treatment and develop a prediction model of clinical remission following adalimumab treatment.</p><p><strong>Design: </strong>Prospective, observational, multicenter study was conducted on moderate-to-severe UC patients (<i>n</i> = 116).</p><p><strong>Methods: </strong>Fecal samples were collected from UC patients at 8 and 56 weeks of adalimumab treatment and from healthy controls (HC, <i>n</i> = 37). Clinical remission was assessed using the Mayo score. Metabolomic and lipidomic analyses were performed using gas chromatography mass spectrometry and nano electrospray ionization mass spectrometry, respectively. Orthogonal partial least squares discriminant analysis was performed to establish a remission prediction model.</p><p><strong>Results: </strong>Fecal metabolites in UC patients markedly differed from those in HC at baseline and were changed similarly to those in HC during treatment; however, lipid profiles did not show these patterns. After treatment, the fecal characteristics of remitters (RM) were closer to those of HC than to those of non-remitters (NRM). At 8 and 56 weeks, amino acid levels in RM were lower than those in NRM and similar to those in HC. After 56 weeks, levels of 3-hydroxybutyrate, lysine, and phenethylamine decreased, and dodecanoate level increased in RM similarly to those in HC. 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引用次数: 0
摘要
背景:溃疡性结肠炎(UC)的治疗靶点和抗肿瘤坏死因子(TNF)治疗结果的预测模型尚未得到充分报道。目的:研究阿达木单抗治疗前后UC患者粪便样本的特征代谢物和脂质谱，并建立阿达木单抗治疗后临床缓解的预测模型。设计:对中重度UC患者进行前瞻性、观察性、多中心研究(n = 116)。方法:收集阿达木单抗治疗8周和56周UC患者以及健康对照(HC, n = 37)的粪便样本。使用Mayo评分评估临床缓解。代谢组学和脂质组学分析分别使用气相色谱质谱和纳米电喷雾质谱进行。采用正交偏最小二乘判别分析建立缓解预测模型。结果:UC患者的粪便代谢物与HC患者在基线时的粪便代谢物明显不同，并且在治疗期间与HC患者的粪便代谢物变化相似;然而，脂质谱没有显示出这些模式。治疗后，汇款者(RM)的粪便特征更接近HC，而非汇款者(NRM)。8周和56周时，RM组的氨基酸水平低于NRM组，与HC组相似。56周后，与HC相似，RM的3-羟基丁酸、赖氨酸和苯乙胺水平下降，十二酸水平升高。基于脂质生物标志物的男性患者长期缓解预测模型比临床标志物表现出更高的性能。结论:UC患者粪便代谢物与HC患者存在明显差异，抗tnf治疗后RM与HC患者粪便代谢物变化相似。此外，3-羟基丁酸盐、赖氨酸、苯乙胺和十二酸酯被认为是UC的潜在治疗靶点。基于脂质生物标志物的长期缓解预测模型可能有助于实施个性化治疗。
Changes in fecal metabolic and lipidomic features by anti-TNF treatment and prediction of clinical remission in patients with ulcerative colitis.
Background: Therapeutic targets for ulcerative colitis (UC) and prediction models of antitumor necrosis factor (TNF) therapy outcomes have not been fully reported.
Objective: Investigate the characteristic metabolite and lipid profiles of fecal samples of UC patients before and after adalimumab treatment and develop a prediction model of clinical remission following adalimumab treatment.
Design: Prospective, observational, multicenter study was conducted on moderate-to-severe UC patients (n = 116).
Methods: Fecal samples were collected from UC patients at 8 and 56 weeks of adalimumab treatment and from healthy controls (HC, n = 37). Clinical remission was assessed using the Mayo score. Metabolomic and lipidomic analyses were performed using gas chromatography mass spectrometry and nano electrospray ionization mass spectrometry, respectively. Orthogonal partial least squares discriminant analysis was performed to establish a remission prediction model.
Results: Fecal metabolites in UC patients markedly differed from those in HC at baseline and were changed similarly to those in HC during treatment; however, lipid profiles did not show these patterns. After treatment, the fecal characteristics of remitters (RM) were closer to those of HC than to those of non-remitters (NRM). At 8 and 56 weeks, amino acid levels in RM were lower than those in NRM and similar to those in HC. After 56 weeks, levels of 3-hydroxybutyrate, lysine, and phenethylamine decreased, and dodecanoate level increased in RM similarly to those in HC. The prediction model of long-term remission in male patients based on lipid biomarkers showed a higher performance than clinical markers.
Conclusion: Fecal metabolites in UC patients markedly differ from those in HC, and the levels in RM are changed similarly to those in HC after anti-TNF therapy. Moreover, 3-hydroxybutyrate, lysine, phenethylamine, and dodecanoate are suggested as potential therapeutic targets for UC. A prediction model of long-term remission based on lipid biomarkers may help implement personalized treatment.
期刊介绍：
Therapeutic Advances in Gastroenterology is an open access journal which delivers the highest quality peer-reviewed original research articles, reviews, and scholarly comment on pioneering efforts and innovative studies in the medical treatment of gastrointestinal and hepatic disorders. The journal has a strong clinical and pharmacological focus and is aimed at an international audience of clinicians and researchers in gastroenterology and related disciplines, providing an online forum for rapid dissemination of recent research and perspectives in this area.
The editors welcome original research articles across all areas of gastroenterology and hepatology.
The journal publishes original research articles and review articles primarily. Original research manuscripts may include laboratory, animal or human/clinical studies – all phases. Letters to the Editor and Case Reports will also be considered.
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