Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Am J Clin Nutr. 2021 Mar 11;113(3):602-611. doi: 10.1093/ajcn/nqaa361.
A processed diet, high in fat and low in fiber, is associated with differences in the gut microbiota and adverse health outcomes in humans; however, little is known about the diet-microbiota relation and its impact on pregnancy. Spontaneous preterm birth (SPTB), a pregnancy outcome with serious short- and long-term consequences, occurs more frequently in black and in obese women in the United States.
In a prospective, case-control sample matched for race and obesity (cases = 16, controls = 32), we compared the fecal gut microbiota, fecal and plasma metabolites, and diet in the late second trimester. We hypothesized that a Western diet would be associated with reduced microbiota richness and a metabolic signature predicting incidence of SPTB.
The fecal microbiota was characterized by 16S-tagged sequencing and untargeted metabolomics was used to analyze both plasma and fecal metabolites. Wilcoxon's rank-sum test was used for the comparison of microbiota genera, α-diversity, fecal and plasma metabolites, and dietary variables between term and SPTB. β-Diversity was analyzed using permutational multivariate ANOVA, and metabolite associations were assessed by module analysis.
A decrease in α-diversity was strongly associated with the development of SPTB, especially in the taxonomic class of Betaproteobacteria. Of 824 fecal metabolites, 22 metabolites (mostly lipids) differed between cases and controls (P < 0.01), with greater DHA (22:6n-3) and EPA (20:5n-3) in cases [false discovery rate (FDR) < 0.2]. The most significant fecal metabolite module (FDR-adjusted P = 0.008) was dominated by DHA and EPA. Dietary saturated fat (primarily palmitate) intake was greater in cases (31.38 ± 7.37 compared with 26.08 ± 8.62 g, P = 0.045) and was positively correlated with fecal DHA and EPA (P < 0.05).
Reduced α-diversity of the gut microbiota and higher excretion of omega-3 (n-3) fatty acids in stool may provide a novel biomarker signature predicting SPTB in women with a low-fiber, high-fat diet. Further investigation of these markers in a larger sample is needed for validation.
富含脂肪和低纤维的加工食品与人类肠道微生物群的差异和不良健康结果有关；然而，人们对饮食-微生物群的关系及其对怀孕的影响知之甚少。自发性早产（SPTB）是一种妊娠结局，对母婴都有严重的短期和长期后果，在美国，黑人女性和肥胖女性的 SPTB 发生率更高。
在一项针对种族和肥胖匹配的前瞻性病例对照样本（病例=16，对照=32）中，我们比较了妊娠晚期的粪便肠道微生物群、粪便和血浆代谢物以及饮食。我们假设西方饮食与微生物丰富度降低以及预测 SPTB 发生的代谢特征有关。
通过 16S 标记测序对粪便微生物群进行特征描述，并使用非靶向代谢组学分析粪便和血浆代谢物。采用 Wilcoxon 秩和检验比较 term 和 SPTB 之间的微生物属、α多样性、粪便和血浆代谢物以及饮食变量。采用置换多元方差分析（PERMANOVA）分析 β 多样性，通过模块分析评估代谢物相关性。
α多样性的降低与 SPTB 的发生密切相关，尤其是在 Betaproteobacteria 分类群中。在 824 种粪便代谢物中，有 22 种代谢物（主要是脂质）在病例和对照组之间存在差异（P<0.01），病例组 DHA（22:6n-3）和 EPA（20:5n-3）更高[假发现率（FDR）<0.2]。最显著的粪便代谢物模块（FDR 调整的 P=0.008）主要由 DHA 和 EPA 组成。病例组的膳食饱和脂肪（主要是棕榈酸）摄入量更高（31.38±7.37 比 26.08±8.62 g，P=0.045），并且与粪便 DHA 和 EPA 呈正相关（P<0.05）。
肠道微生物群 α 多样性降低和粪便中 ω-3（n-3）脂肪酸排泄增加可能为低纤维、高脂肪饮食的女性预测 SPTB 提供新的生物标志物特征。需要在更大的样本中进一步研究这些标志物以进行验证。
