University of Liverpool Institute of Systems, Molecular and Integrative Biology, Liverpool, UK; Liverpool University Hospitals NHS Foundation Trust, Department of Gastroenterology, Liverpool, UK.
University of Liverpool Institute of Systems, Molecular and Integrative Biology, Liverpool, UK.
EBioMedicine. 2024 Sep;107:105282. doi: 10.1016/j.ebiom.2024.105282. Epub 2024 Aug 22.
Irritable bowel syndrome (IBS) is a common and debilitating disorder manifesting with abdominal pain and bowel dysfunction. A mainstay of treatment is dietary modification, including restriction of FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols). A greater response to a low FODMAP diet has been reported in those with a distinct IBS microbiome termed IBS-P. We investigated whether this is linked to specific changes in the metabolome in IBS-P.
Solid phase microextraction gas chromatography-mass spectrometry was used to examine the faecal headspace of 56 IBS cases (each paired with a non-IBS household control) at baseline, and after four-weeks of a low FODMAP diet (39 pairs). 50% cases had the IBS-P microbial subtype, while the others had a microbiome that more resembled healthy controls (termed IBS-H). Clinical response to restriction of FODMAPs was measured with the IBS-symptom severity scale, from which a pain sub score was calculated.
Two distinct metabotypes were identified and mapped onto the microbial subtypes. IBS-P was characterised by a fermentative metabolic profile rich in short chain fatty acids (SCFAs). After FODMAP restriction significant reductions in SCFAs were observed in IBS-P. SCFA levels did not change significantly in the IBS-H group. The magnitude of pain and overall symptom improvement were significantly greater in IBS-P compared to IBS-H (p = 0.016 and p = 0.026, respectively). Using just five metabolites, a biomarker model could predict microbial subtype with accuracy (AUROC 0.797, sensitivity 78.6% (95% CI: 0.78-0.94), specificity 71.4% (95% CI: 0.55-0.88).
A metabotype high in SCFAs can be manipulated by restricting fermentable carbohydrate, and is associated with an enhanced clinical response to this dietary restriction. This implies that SCFAs harbour pro-nociceptive potential when produced in a specific IBS niche. By ascertaining metabotype, microbial subtype can be predicted with accuracy. This could allow targeted FODMAP restriction in those seemingly primed to respond best.
This research was co-funded by Addenbrooke's Charitable Trust, Cambridge University Hospitals and the Wellcome Sanger Institute, and supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014).
肠易激综合征（IBS）是一种常见且使人虚弱的疾病，其特征为腹痛和肠道功能紊乱。治疗的主要方法是饮食调整，包括限制可发酵寡糖、二糖、单糖和多元醇（FODMAPs）。在具有特定 IBS 微生物组的患者中，低 FODMAP 饮食的反应更大，该微生物组被称为 IBS-P。我们研究了这是否与 IBS-P 中的代谢组特定变化有关。
采用固相微萃取气相色谱-质谱法检测 56 例 IBS 患者（每例均与非 IBS 家庭对照配对）的粪便顶空，基线时和低 FODMAP 饮食四周后（39 对）进行检测。50%的患者具有 IBS-P 微生物亚型，而其他患者的微生物组更类似于健康对照（称为 IBS-H）。使用 IBS 症状严重程度量表测量对 FODMAP 限制的临床反应，由此计算疼痛子评分。
确定了两种不同的代谢类型，并将其映射到微生物亚型上。IBS-P 的特点是富含短链脂肪酸（SCFAs）的发酵代谢特征。在限制 FODMAP 后，IBS-P 中 SCFAs 显著减少。IBS-H 组的 SCFA 水平没有显著变化。与 IBS-H 相比，IBS-P 的疼痛和整体症状改善幅度明显更大（p=0.016 和 p=0.026）。仅使用五种代谢物，生物标志物模型即可准确预测微生物亚型（AUROC 0.797，敏感性 78.6%（95%CI：0.78-0.94），特异性 71.4%（95%CI：0.55-0.88）。
富含 SCFAs 的代谢类型可以通过限制可发酵碳水化合物来调节，并且与对这种饮食限制的增强临床反应有关。这意味着当在特定的 IBS 生态位中产生时，SCFAs 具有潜在的致痛作用。通过确定代谢类型，可以准确预测微生物亚型。这可以使那些似乎最有可能做出最佳反应的人有针对性地限制 FODMAP。
这项研究由 Addenbrooke's Charitable Trust、剑桥大学医院和 Wellcome Sanger 研究所共同资助，并得到了 NIHR 剑桥生物医学研究中心（BRC-1215-20014）的支持。
