Kaundal Shaweta, Patil Amol N, Ks Lekshmon, Sharma Vishal, Arora Amit, Singh Charanpreet, Jandial Aditya, Jain Arihant, Prakash Gaurav, Khadwal Alka, Malhotra Pankaj, Lad Deepesh P
Clinical Hematology & Medical Oncology.
Clinical Pharmacology.
Blood Cell Ther. 2024 Aug 30;7(4):101-105. doi: 10.31547/bct-2024-007. eCollection 2024 Nov 25.
The gut microbiome has an established role in allogeneic hematopoietic cell transplantation (allo-HCT), but not in an auto-HCT setting. We have hypothesized that fecal short-chain fatty acids (SCFA) and urinary 3-indoxyl sulfate (3-IS), which are metabolites derived from the action of the gut microbiome on dietary fiber, play a role in auto-HCT outcomes.
This was a single-center prospective study involving auto-HCT recipients. Baseline patient and disease details, diet diaries, and antibiotic exposure were recorded in consenting patients. Serial (pre-HCT, week two, and week four post-HCT) SCFA and urine 3-IS levels were measured using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). HCT outcomes were correlated with these metabolites.
Thirty patients (myeloma, n=13; lymphoma, n=17) were analyzed. The levels of urinary 3-IS, fecal acetate, propionate, and butyrate were found to be decreased at week two and were recovered by week four post-HCT. Those with low median nadir fecal butyrate levels at week two also had significantly lower pre-HCT and week four butyrate levels. Recipients with low butyrate levels had more grade ≥2 mucositis (80% vs. 33%, =0.01) and low fiber intake (10.4 g vs. 13.6 g, =0.04). They also had more carbapenem exposure (93% vs. 47%, =0.005) and prolonged antibiotics (11 days vs. 8 days, =0.008). There were no differences in the time to neutrophil or platelet engraftment, mortality, or disease response.
Low pre-HCT fecal butyrate levels tend to persist post-HCT and they are associated with mucositis, dietary fiber intake, and antibiotic exposure. The gut microbiome and its modulation may play a role in auto-HCT settings.
肠道微生物群在异基因造血细胞移植（allo-HCT）中已被证实发挥作用，但在自体造血细胞移植（auto-HCT）环境中并非如此。我们推测，粪便短链脂肪酸（SCFA）和尿中3-吲哚硫酸盐（3-IS），这些是肠道微生物群对膳食纤维作用产生的代谢产物，在自体造血细胞移植结果中发挥作用。
这是一项涉及自体造血细胞移植受者的单中心前瞻性研究。在同意参与的患者中记录基线患者和疾病详情、饮食日记以及抗生素暴露情况。使用液相色谱-质谱/质谱（LC-MS/MS）测量系列（移植前、移植后第2周和第4周）SCFA和尿中3-IS水平。造血细胞移植结果与这些代谢产物相关。
分析了30例患者（骨髓瘤，n = 13；淋巴瘤，n = 17）。发现尿中3-IS、粪便乙酸盐、丙酸盐和丁酸盐水平在第2周时降低，并在移植后第4周恢复。第2周粪便丁酸盐最低中位数水平较低的患者，其移植前和第4周的丁酸盐水平也显著较低。丁酸盐水平低的受者有更多≥2级黏膜炎（80%对33%，P = 0.01）且膳食纤维摄入量低（10.4克对13.6克，P = 0.04）。他们也有更多碳青霉烯类药物暴露（93%对47%，P = 0.005）和抗生素使用时间延长（11天对8天，P = 0.008）。中性粒细胞或血小板植入时间、死亡率或疾病反应方面无差异。
移植前粪便丁酸盐水平低在移植后往往持续存在，且与黏膜炎、膳食纤维摄入量和抗生素暴露有关。肠道微生物群及其调节可能在自体造血细胞移植环境中发挥作用。
