Gut microbiota in children hospitalized with severe acute malnutrition in Uganda. Gut microbiota in children hospitalized with oedematous and non-oedematous severe acute malnutrition in Uganda

Abstract Background Severe acute malnutrition (SAM) among children remains a major health problem in many developing countries. SAM manifests in both an oedematous and a non-oedematous form, with oedematous malnutrition in its most severe form also known as kwashiorkor. The pathogenesis of both types of malnutrition in children remains largely unknown, but gut microbiota (GM) dysbiosis has recently been linked to oedematous malnutrition. In the present study we aimed to assess whether GM composition differed between Ugandan children suffering from either oedematous or non-oedematous malnutrition. Methodology/Principal Findings As part of an observational study among children hospitalized with SAM aged 6-24 months in Uganda, fecal samples were collected at admission. Total genomic DNA was extracted from fecal samples and PCR amplification was performed followed by denaturing gradient gel electrophoresis and tag-encoded 16S rRNA gene-targeted high throughput amplicon sequencing. Alpha and beta diversity measures were determined along with ANOVA mean relative abundance and G-test of independence followed by comparisons between groups. Of the 87 SAM children included, 62% suffered from oedematous malnutrition, 38% non-oedematous malnutrition, 66% were boys and the mean age was 16,1 months. GM composition was found to differ between the two groups of children as determined by DGGE (p=0.0317) and by high-throughput sequencing with non-oedematous children having lower GM alpha diversity (p=0.036). However, beta diversity analysis did not reveal larger differences between the GM of children with oedematous and non-oedematous SAM (ANOSIM analysis, weighted uniFrac, R=-0.0085, p=0.584; unweighted uniFrac, R=0.0719, p=0.011). Conclusions/Significance Our results showed that non-oedematous SAM children have lower GM diversity compared to oedematous SAM children, however were not able to identify any clear compositional differences.

**摘要**
**背景** 儿童严重急性营养不良（Severe acute malnutrition, SAM）仍是诸多发展中国家面临的重大公共卫生挑战。严重急性营养不良分为水肿型与非水肿型两种表型，其中病情最严重的水肿型营养不良又称夸希奥科病（kwashiorkor）。目前儿童两类营养不良的发病机制仍未完全阐明，但近期研究发现肠道菌群（gut microbiota, GM）失调与水肿型营养不良存在关联。本研究旨在探讨乌干达水肿型与非水肿型严重急性营养不良儿童的肠道菌群组成是否存在差异。

**方法/主要结果** 本研究作为一项观察性研究的一部分，纳入乌干达6~24月龄因严重急性营养不良住院的儿童，于入院时采集粪便样本。从粪便样本中提取总基因组DNA，经PCR扩增后，依次采用变性梯度凝胶电泳（denaturing gradient gel electrophoresis）与标签编码16S rRNA基因靶向高通量扩增子测序进行检测。计算α多样性与β多样性指标，并结合方差分析（ANOVA）平均相对丰度、独立性G检验开展组间比较。
本研究共纳入87名严重急性营养不良儿童，其中62%为水肿型营养不良患儿，38%为非水肿型营养不良患儿；男性占比66%，平均年龄为16.1月龄。
变性梯度凝胶电泳检测结果显示，两组儿童的肠道菌群组成存在显著差异（p=0.0317）；高通量测序结果亦表明，非水肿型营养不良患儿的肠道菌群α多样性更低（p=0.036）。不过，β多样性分析未发现水肿型与非水肿型SAM患儿的肠道菌群存在显著组间差异（相似性分析ANOSIM：加权UniFrac，R=-0.0085，p=0.584；非加权UniFrac，R=0.0719，p=0.011）。

**结论与意义** 本研究结果显示，非水肿型严重急性营养不良患儿的肠道菌群多样性低于水肿型患儿，但未明确二者肠道菌群组成存在显著差异。