Lu Gaochen, Zhang Sheng, Wang Rui, Wu Xia, Chen Yaoyao, Wen Quan, Cui Bota, Zhang Faming, Li Pan
Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, Jiangsu, China.
Key Lab of Holistic Integrative Enterology, Jiangsu Engineering Research Center for Advanced Microbiota Medicine, Nanjing Medical University, Nanjing, 210011, Jiangsu, China.
BMC Med. 2025 Sep 1;23(1):511. doi: 10.1186/s12916-025-04353-y.
Bile acid malabsorption (BAM) or bile acid diarrhea (BAD) complicates more than 30% of Crohn's disease (CD), yet no non-invasive biomarker reliably identifies patients who will benefit from fecal microbiota transplantation (FMT). We investigated whether serum 7α-hydroxy-4-cholesten-3-one (C4), a hepatic bile-acid synthesis precursor, can predict BAM and FMT response in inflammatory bowel disease (IBD).
We included 106 pairs of IBD patients treated with FMT from two longitudinal cohorts of prospective trials and 24 matched healthy individuals to identify a multi-omics analysis of microbiota-metabolism and evaluate real-world effectiveness of FMT. Fecal and serum samples before and after FMT along with medical information were collected and detected through 16S rRNA amplicon sequencing and untargeted liquid chromatography mass spectrometry. Mice models were used to preliminarily verify the exacerbation of colitis through administration of primary BAs and treated by FMT.
Patients in BAM group tended to achieve sustained higher and stable clinical response (66.67% vs. 49.41%) and remission (52.38% vs. 40.00%) than non-BAM group at 3 months after FMT, along with a significantly decrease of C4 (P < 0.001), improvement of obvious abdominal pain and diarrhea, which was especially obvious in CD patients with ileal resection and ileal /ileocolonic type. Random forest classifiers predicted BAM in IBD patients with 18 or top 4 differential OTUs, showing an area under the curve of 0.92 and 0.83, respectively. Furthermore, results from primary bile acid-induced colitis mice models reinforced these findings.
Serum C4 and a minimal gut microbiota may identify IBD patients with BAM who are most likely to achieve durable remission after FMT. These translatable biomarkers can guide precision use of microbiota-directed therapy.
ClinicalTrials.gov: NCT01790061 and NCT01793831.
胆汁酸吸收不良（BAM）或胆汁酸腹泻（BAD）使超过30%的克罗恩病（CD）病情复杂化，但尚无可靠的非侵入性生物标志物能识别出可从粪便微生物群移植（FMT）中获益的患者。我们研究了血清7α-羟基-4-胆甾烯-3-酮（C4）这一肝脏胆汁酸合成前体，是否能预测炎症性肠病（IBD）中的BAM及FMT反应。
我们纳入了来自两项前瞻性试验纵向队列的106对接受FMT治疗的IBD患者以及24名匹配的健康个体，以开展微生物群-代谢的多组学分析，并评估FMT在现实世界中的有效性。收集FMT前后的粪便和血清样本以及医疗信息，通过16S rRNA扩增子测序和非靶向液相色谱质谱法进行检测。使用小鼠模型通过给予初级胆汁酸来初步验证结肠炎的恶化情况，并采用FMT进行治疗。
在FMT后3个月时，BAM组患者相较于非BAM组，更倾向于实现持续更高且稳定的临床反应（66.67%对49.41%）和缓解（52.38%对40.00%），同时C4显著降低（P < 0.001），腹痛和腹泻明显改善，这在回肠切除及回肠/回结肠型的CD患者中尤为明显。随机森林分类器利用18个或前4个差异操作分类单元（OTU）预测IBD患者中的BAM，曲线下面积分别为0.92和0.83。此外，初级胆汁酸诱导的结肠炎小鼠模型的结果强化了这些发现。
血清C4和最少的肠道微生物群可能识别出在FMT后最有可能实现持久缓解的患有BAM的IBD患者。这些可转化的生物标志物可指导微生物群导向疗法的精准应用。
ClinicalTrials.gov：NCT0179 .0061和NCT01793831。
