Objective Reducing FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) can be clinically beneficial in IBS but the mechanism is incompletely understood. We aimed to detect microbial signatures that might predict response to the low FODMAP diet and assess whether microbiota compositional and functional shifts could provide insights into its mode of action. Design We used metagenomics to determine high-resolution taxonomic and functional profiles of the stool microbiota from IBS cases and household controls (n=56 pairs) on their usual diet. Clinical response and microbiota changes were studied in 41 pairs after 4 weeks on a low FODMAP diet. Results Unsupervised analysis of baseline IBS cases pre-diet identified two distinct microbiota profiles, which we refer to as IBSP (pathogenic-like) and IBSH (health-like) subtypes. IBSP microbiomes were enriched in Firmicutes and genes for amino acid and carbohydrate metabolism, but depleted in Bacteroidetes species. IBSH microbiomes were similar to controls. On the low FODMAP diet, IBSH and control microbiota were unaffected, but the IBSP signature shifted towards a health-associated microbiome with an increase in Bacteroidetes (p=0.009), a decrease in Firmicutes species (p=0.004) and normalisation of primary metabolic genes. The clinical response to the low FODMAP diet was greater in IBSP subjects compared with IBSH (p=0.02). Conclusion 50% of IBS cases manifested a ‘pathogenic’ gut microbial signature. This shifted towards the healthy profile on the low FODMAP diet; and IBSP cases showed an enhanced clinical responsiveness to the dietary therapy. The effectiveness of FODMAP reduction in IBSP may result from the alterations in gut microbiota and metabolites produced. Microbiota signatures could be useful as biomarkers to guide IBS treatment; and investigating IBSP species and metabolic pathways might yield insights regarding IBS pathogenic mechanisms. Data are available in a public, open access repository. Raw sequencing data are accessible under ENA Study Accession Number: ERP021923Processed data are submitted as supplementary materials.Source code and scripts necessary to replicate the analysis are submitted at .

中文翻译：

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肠易激综合征中发现的两种微生物亚型对低 FODMAP 饮食有不同的反应

目的 减少 FODMAP（可发酵寡糖、二糖、单糖和多元醇）对 IBS 具有临床益处，但其机制尚不完全清楚。我们的目的是检测可能预测对低 FODMAP 饮食反应的微生物特征，并评估微生物群组成和功能的变化是否可以深入了解其作用模式。设计我们使用宏基因组学来确定 IBS 病例和家庭对照（n=56 对）日常饮食中粪便微生物群的高分辨率分类和功能特征。研究人员对 41 对低 FODMAP 饮食 4 周后的临床反应和微生物群变化进行了研究。结果 对饮食前基线 IBS 病例的无监督分析确定了两种不同的微生物群特征，我们将其称为 IBSP（致病样）和 IBSH（健康样）亚型。IBSP 微生物群在厚壁菌门以及氨基酸和碳水化合物代谢基因中富集，但在拟杆菌属中却有所减少。IBSH 微生物组与对照组相似。在低 FODMAP 饮食中，IBSH 和对照微生物群未受影响，但 IBSP 特征转向与健康相关的微生物组，拟杆菌门增加 (p=0.009)，厚壁菌门物种减少 (p=0.004)，初级代谢正常化基因。与 IBSH 相比，IBSP 受试者对低 FODMAP 饮食的临床反应更大 (p=0.02)。结论 50% 的 IBS 病例表现出“致病性”肠道微生物特征。这转向了低 FODMAP 饮食的健康状况；IBSP 病例显示出对饮食疗法的临床反应增强。FODMAP 减少 IBSP 的有效性可能是由于肠道微生物群和产生的代谢物的改变所致。微生物群特征可作为指导 IBS 治疗的生物标志物；研究 IBSP 种类和代谢途径可能会产生有关 IBS 致病机制的见解。数据可在公共、开放访问存储库中获取。原始测序数据可通过 ENA 研究登录号获取：ERP021923处理后的数据作为补充材料提交。复制分析所需的源代码和脚本提交于。