Aim

The metabolic performance of the gut microbiota contributes to the onset of type 2 diabetes. However, targeted dietary interventions are limited by the highly variable inter-individual response. We hypothesized (1) that the composition of the complex gut microbiome and metabolome (MIME) differ across metabolic spectra (lean-obese-diabetes); (2) that specific MIME patterns could explain the differential responses to dietary inulin; and (3) that the response can be predicted based on baseline MIME signature and clinical characteristics.

Method

Forty-nine patients with newly diagnosed pre/diabetes (DM), 66 metabolically healthy overweight/obese (OB), and 32 healthy lean (LH) volunteers were compared in a cross-sectional case-control study integrating clinical variables, dietary intake, gut microbiome, and fecal/serum metabolomes (16 S rRNA sequencing, metabolomics profiling). Subsequently, 27 DM were recruited for a predictive study: 3 months of dietary inulin (10 g/day) intervention.

Results

MIME composition was different between groups. While the DM and LH groups represented opposite poles of the abundance spectrum, OB was closer to DM. Inulin supplementation was associated with an overall improvement in glycemic indices, though the response was very variable, with a shift in microbiome composition toward a more favorable profile and increased serum butyric and propionic acid concentrations. The improved glycemic outcomes of inulin treatment were dependent on better baseline glycemic status and variables related to the gut microbiota, including the abundance of certain bacterial taxa (i.e., Blautia, Eubacterium halii group, Lachnoclostridium, Ruminiclostridium, Dialister, or Phascolarctobacterium), serum concentrations of branched-chain amino acid derivatives and asparagine, and fecal concentrations of indole and several other volatile organic compounds.

Conclusion

We demonstrated that obesity is a stronger determinant of different MIME patterns than impaired glucose metabolism. The large inter-individual variability in the metabolic effects of dietary inulin was explained by differences in baseline glycemic status and MIME signatures. These could be further validated to personalize nutritional interventions in patients with newly diagnosed diabetes.

中文翻译：

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新发糖尿病的多组学特征预测饮食菊粉的代谢反应：一项观察性研究的结果，随后进行了一项干预性试验

目的

肠道微生物群的代谢表现有助于 2 型糖尿病的发生。然而，有针对性的饮食干预受到高度可变的个体间反应的限制。我们假设 (1) 复杂的肠道微生物组和代谢组 (MIME) 的组成因代谢谱（瘦型-肥胖-糖尿病）而异；(2) 特定的 MIME 模式可以解释对膳食菊粉的不同反应；(3) 可以根据基线 MIME 签名和临床特征预测响应。

方法

在横断面病例对照研究中比较了 49 名新诊断的前期/糖尿病 (DM) 患者、66 名代谢健康的超重/肥胖 (OB) 和 32 名健康瘦 (LH) 志愿者，该研究整合了临床变量、饮食摄入、肠道微生物组和粪便/血清代谢组（16 S rRNA 测序、代谢组学分析）。随后，招募了 27 名 DM 进行预测性研究：3 个月的饮食菊粉（10 克/天）干预。

结果

各组之间的 MIME 组成不同。虽然 DM 和 LH 组代表丰度谱的相反两极，但 OB 更接近 DM。补充菊粉与血糖指数的整体改善有关，尽管反应非常多变，微生物组组成向更有利的方向转变，血清丁酸和丙酸浓度增加。菊糖治疗改善的血糖结果取决于更好的基线血糖状态和与肠道微生物群相关的变量，包括某些细菌类群的丰度（即 Blautia、Eubacterium halii 组、Lachnoclostridium、Ruminiclostridium、Dialister 或考拉杆菌属）)、支链氨基酸衍生物和天冬酰胺的血清浓度，以及吲哚和其他几种挥发性有机化合物的粪便浓度。

结论

我们证明，与葡萄糖代谢受损相比，肥胖是不同 MIME 模式的更强决定因素。基线血糖状态和 MIME 特征的差异解释了膳食菊粉代谢影响的巨大个体间差异。这些可以进一步验证，以对新诊断的糖尿病患者进行个性化的营养干预。