Infectious Disease & Microbiome Program, Broad Institute, 415 Main Street, Cambridge, MA, 02142, USA.
Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
BMC Microbiol. 2021 Feb 18;21(1):53. doi: 10.1186/s12866-021-02106-4.
Urinary tract infections (UTIs) affect 15 million women each year in the United States, with > 20% experiencing frequent recurrent UTIs. A recent placebo-controlled clinical trial found a 39% reduction in UTI symptoms among recurrent UTI sufferers who consumed a daily cranberry beverage for 24 weeks. Using metagenomic sequencing of stool from a subset of these trial participants, we assessed the impact of cranberry consumption on the gut microbiota, a reservoir for UTI-causing pathogens such as Escherichia coli, which causes > 80% of UTIs.
The overall taxonomic composition, community diversity, carriage of functional pathways and gene families, and relative abundances of the vast majority of observed bacterial taxa, including E. coli, were not changed significantly by cranberry consumption. However, one unnamed Flavonifractor species (OTU41), which represented ≤1% of the overall metagenome, was significantly less abundant in cranberry consumers compared to placebo at trial completion. Given Flavonifractor's association with negative human health effects, we sought to determine OTU41 characteristic genes that may explain its differential abundance and/or relationship to key host functions. Using comparative genomic and metagenomic techniques, we identified genes in OTU41 related to transport and metabolism of various compounds, including tryptophan and cobalamin, which have been shown to play roles in host-microbe interactions.
While our results indicated that cranberry juice consumption had little impact on global measures of the microbiome, we found one unnamed Flavonifractor species differed significantly between study arms. This suggests further studies are needed to assess the role of cranberry consumption and Flavonifractor in health and wellbeing in the context of recurrent UTI.
Clinical trial registration number: ClinicalTrials.gov NCT01776021 .
在美国,每年有 1500 万女性受到尿路感染(UTI)的影响,其中>20%的人患有频繁复发性 UTI。最近一项安慰剂对照临床试验发现,在 24 周内每天饮用蔓越莓饮料的复发性 UTI 患者中,UTI 症状减少了 39%。使用这些试验参与者的粪便进行宏基因组测序,我们评估了蔓越莓消费对肠道微生物群的影响,肠道微生物群是引起尿路感染的病原体(如引起超过 80%的尿路感染的大肠杆菌)的储存库。
蔓越莓消费并未显著改变总体分类组成、群落多样性、功能途径和基因家族的携带情况,以及绝大多数观察到的细菌分类群的相对丰度,包括大肠杆菌。然而,在试验结束时,一种未命名的 Flavonifractor 物种(OTU41),占总体宏基因组的比例≤1%,在蔓越莓消费者中明显比安慰剂组少。鉴于 Flavonifractor 与人类健康的负面影响有关,我们试图确定 OTU41 的特征基因,这些基因可能解释其丰度的差异及其与关键宿主功能的关系。使用比较基因组学和宏基因组学技术,我们在 OTU41 中鉴定了与各种化合物(包括色氨酸和钴胺素)的转运和代谢相关的基因,这些化合物已被证明在宿主-微生物相互作用中发挥作用。
虽然我们的结果表明蔓越莓汁消费对微生物组的全局测量影响不大,但我们发现研究组之间的一种未命名的 Flavonifractor 物种存在显著差异。这表明需要进一步研究来评估蔓越莓消费和 Flavonifractor 在复发性 UTI 背景下对健康和幸福感的作用。
临床试验注册号:ClinicalTrials.gov NCT01776021。