Identification of distinct stool metabolites in women with endometriosis for non-invasive diagnosis and potential for microbiota-based therapies.

IF 12.8 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Med Pub Date : 2024-10-03 DOI:10.1016/j.medj.2024.09.006
Chandni Talwar, Goutham Venkata Naga Davuluri, Abu Hena Mostafa Kamal, Cristian Coarfa, Sang Jun Han, Surabi Veeraragavan, Krishna Parsawar, Nagireddy Putluri, Kristi Hoffman, Patricia Jimenez, Scott Biest, Ramakrishna Kommagani
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Abstract

Background: Endometriosis, a poorly studied gynecological condition, is characterized by the presence of ectopic endometrial lesions resulting in pelvic pain, inflammation, and infertility. These associated symptoms contribute to a significant burden, often exacerbated by delayed diagnosis. Current diagnostic methods involve invasive procedures, and existing treatments provide no cure.

Methods: Microbiome-metabolome signatures in stool samples from individuals with and without endometriosis were determined using unbiased metabolomics and 16S bacteria sequencing. Functional studies for selected microbiota-derived metabolites were conducted in vitro using patient-derived cells and in vivo by employing murine and human xenograft pre-clinical disease models.

Findings: We discovered a unique bacteria-derived metabolite signature intricately linked to endometriosis. The altered fecal metabolite profile exhibits a strong correlation with that observed in inflammatory bowel disease (IBD), revealing intriguing connections between these two conditions. Notably, we validated 4-hydroxyindole, a gut-bacteria-derived metabolite that is lower in stool samples of endometriosis. Extensive in vivo studies found that 4-hydroxyindole suppressed the initiation and progression of endometriosis-associated inflammation and hyperalgesia in heterologous mouse and in pre-clinical models of the disease.

Conclusions: Our findings are the first to provide a distinct stool metabolite signature in women with endometriosis, which could serve as stool-based non-invasive diagnostics. Further, the gut-microbiota-derived 4-hydroxyindole poses as a therapeutic candidate for ameliorating endometriosis.

Funding: This work was funded by the NIH/NICHD grants (R01HD102680, R01HD104813) and a Research Scholar Grant from the American Cancer Society to R.K.

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鉴定患有子宫内膜异位症妇女的不同粪便代谢物,以进行非侵入性诊断,并挖掘基于微生物群疗法的潜力。
背景:子宫内膜异位症是一种研究较少的妇科疾病,其特点是存在异位的子宫内膜病变,导致盆腔疼痛、炎症和不孕。这些相关症状给患者带来了沉重的负担,而延误诊断往往又会加重病情。目前的诊断方法涉及侵入性程序,现有的治疗方法也无法治愈:方法:采用无偏代谢组学和 16S 细菌测序法确定了子宫内膜异位症患者和非子宫内膜异位症患者粪便样本中的微生物组代谢组特征。在体外使用患者衍生细胞,在体内使用小鼠和人类异种移植临床前疾病模型,对选定的微生物群衍生代谢物进行了功能研究:我们发现了一种与子宫内膜异位症密切相关的独特细菌衍生代谢物特征。粪便代谢物特征的改变与炎症性肠病(IBD)中观察到的代谢物特征有很强的相关性,揭示了这两种疾病之间耐人寻味的联系。值得注意的是,我们验证了子宫内膜异位症患者粪便样本中含量较低的肠道细菌衍生代谢物--4-羟基吲哚。广泛的体内研究发现,在异源小鼠和子宫内膜异位症临床前模型中,4-羟基吲哚抑制了子宫内膜异位症相关炎症和痛觉减退的发生和发展:我们的研究结果首次为子宫内膜异位症妇女提供了独特的粪便代谢物特征,可作为基于粪便的非侵入性诊断。此外,肠道微生物群衍生的 4-羟基吲哚可作为改善子宫内膜异位症的候选疗法:本研究由美国国立卫生研究院/美国国家癌症研究与发展中心(NIH/NICHD)资助(R01HD102680、R01HD104813),R.K.获得了美国癌症协会(American Cancer Society)的研究学者资助(Research Scholar Grant)。
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来源期刊
Med
Med MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
17.70
自引率
0.60%
发文量
102
期刊介绍: Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically. Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.
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