Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
Microbiol Spectr. 2023 Jun 15;11(3):e0527322. doi: 10.1128/spectrum.05273-22. Epub 2023 May 18.
The World Health Organization recommends untargeted iron supplementation for women of reproductive age (WRA) in countries where anemia prevalence is greater than 40%, such as Cambodia. Iron supplements, however, often have poor bioavailability, so the majority remains unabsorbed in the colon. The gut houses many iron-dependent bacterial enteropathogens; thus, providing iron to individuals may be more harmful than helpful. We examined the effects of two oral iron supplements with differing bioavailability on the gut microbiomes in Cambodian WRA. This study is a secondary analysis of a double-blind, randomized controlled trial of oral iron supplementation in Cambodian WRA. For 12 weeks, participants received ferrous sulfate, ferrous bisglycinate, or placebo. Participants provided stool samples at baseline and 12 weeks. A subset of stool samples (= 172), representing the three groups, were randomly selected for gut microbial analysis by 16S rRNA gene sequencing and targeted real-time PCR (qPCR). At baseline, 1% of women had iron-deficiency anemia. The most abundant gut phyla were Bacteroidota (45.7%) and Firmicutes (42.1%). Iron supplementation did not alter gut microbial diversity. Ferrous bisglycinate increased the relative abundance of and there was a trend towards an increase in the relative abundance of Escherichia qPCR detected an increase in the enteropathogenic Escherichia coli (EPEC) virulence gene, , in the group that received ferrous sulfate. Thus, iron supplementation did not affect overall gut bacterial diversity in predominantly iron-replete Cambodian WRA, however, evidence does suggest an increase in relative abundance within the broad family associated with ferrous bisglycinate use. To the best of our knowledge, this is the first published study to characterize the effects of oral iron supplementation on the gut microbiomes of Cambodian WRA. Our study found that iron supplementation with ferrous bisglycinate increases the relative abundance of , which is a family of bacteria that includes many Gram-negative enteric pathogens like Salmonella, , and Escherichia coli. Using qPCR for additional analysis, we were able to detect genes associated with enteropathogenic E. coli, a type of diarrheagenic E. coli known to be present around the world, including water systems in Cambodia. The current WHO guidelines recommend blanket (untargeted) iron supplementation for Cambodian WRA despite a lack of studies in this population examining iron's effect on the gut microbiome. This study can facilitate future research that may inform evidence-based global practice and policy.
世界卫生组织建议在贫血患病率大于 40%的生殖年龄妇女（WRA）所在国家进行非靶向铁补充，例如柬埔寨。然而，铁补充剂通常生物利用度较差，因此大部分仍未被结肠吸收。肠道中有许多依赖铁的肠道病原体；因此，给个体提供铁可能弊大于利。我们研究了两种具有不同生物利用度的口服铁补充剂对柬埔寨 WRA 肠道微生物组的影响。本研究是对柬埔寨 WRA 口服铁补充剂双盲、随机对照试验的二次分析。在 12 周的时间里，参与者接受硫酸亚铁、甘氨酸亚铁或安慰剂。参与者在基线和 12 周时提供粪便样本。从三组中随机选择一小部分粪便样本（=172），通过 16S rRNA 基因测序和靶向实时 PCR（qPCR）进行肠道微生物分析。在基线时，1%的女性患有缺铁性贫血。最丰富的肠道菌门是拟杆菌门（45.7%）和厚壁菌门（42.1%）。铁补充剂没有改变肠道微生物多样性。甘氨酸亚铁增加了 和 的相对丰度，并且在接受硫酸亚铁的组中，大肠杆菌（Escherichia coli）的相对丰度呈增加趋势。因此，铁补充剂并未影响主要铁充足的柬埔寨 WRA 的总体肠道细菌多样性，但是，有证据表明，在广泛的家族中，与甘氨酸亚铁的使用相关的相对丰度增加。据我们所知，这是第一项描述口服铁补充剂对柬埔寨 WRA 肠道微生物组影响的已发表研究。我们的研究发现，甘氨酸亚铁的铁补充剂增加了 的相对丰度，这是一个包括许多革兰氏阴性肠道病原体的细菌家族，如沙门氏菌、志贺氏菌和大肠杆菌。通过 qPCR 进行额外分析，我们能够检测到与肠致病性大肠杆菌相关的基因，肠致病性大肠杆菌是一种已知在世界各地存在的腹泻性大肠杆菌，包括柬埔寨的水系统。目前的世界卫生组织指南建议对柬埔寨 WRA 进行全面（非靶向）铁补充，尽管在该人群中缺乏研究来检查铁对肠道微生物组的影响。这项研究可以为未来的研究提供便利，这些研究可能为循证全球实践和政策提供信息。
