Peripheral Blood Microbiome Analysis via Noninvasive Prenatal Testing Reveals the Complexity of Circulating Microbial Cell-Free DNA

Abstract

While circulating cell-free DNA (cfDNA) has been becoming a powerful marker for noninvasive identification of infectious pathogens in liquid biopsy specimens, a baseline for microbial cfDNA in healthy individuals is urgently needed for the proper interpretation of microbial cfDNA sequencing results in clinical metagenomics. Standard low-pass whole-genome-sequencing-based NIPT shares many similarities with the sequencing protocol for metagenomics and could provide a microbial cfDNA baseline in healthy people; thus, a reference cfDNA data set of the human microbiome was established with sequencing data from a total of 107,763 peripheral blood samples of healthy pregnant women undergoing NIPT screening.

The Blood Microbiome and Health: Current Evidence, Controversies, and Challenges

“…Leveraging the concept of the multibiome, which delineates the interaction between different microbial entities (i.e., bacteria, fungi and viruses) as a community, a recent study revealed fascinating links between signatures of the blood microbiome and pathogens known to inflict pregnancy-related complications, namely Toxoplasma gondii , Hepatitis B virus, Human Papillomavirus (HPV), Rubella virus, Cytomegalovirus and Herpes simplex virus (HSV) [ 67 ]. For example, HPV positive blood samples were linked to elevated Weissella paramesenteroides and Propionibacterium acne, while blood samples positive for HSV had higher abundance of Bifidobacterium bifidum and Propionibacterium acne [ 67 ]. Toxoplasma gondii also has a high tendency to co-occur with Pectobacterium carotovorum and Chthoniobacter flavus in blood [ 67 ].…”

“…For example, HPV positive blood samples were linked to elevated Weissella paramesenteroides and Propionibacterium acne, while blood samples positive for HSV had higher abundance of Bifidobacterium bifidum and Propionibacterium acne [ 67 ]. Toxoplasma gondii also has a high tendency to co-occur with Pectobacterium carotovorum and Chthoniobacter flavus in blood [ 67 ]. Essentially, the variations in the blood microbiome and co-occurrence of harmful pathogens with other microbes could be invaluable for the development of newer stratification strategy to identify mothers with a high risk for pregnancy-related complications via non-invasive maternal blood analysis.…”

Bioresource collection of blood components from pregnant women to identify fetal genetic features, as well as to search for genetic markers of gestational complications

“…Однако эти данные зачастую противоречивы, их недостаточно для использования в клинической практике, поэтому необходимы дальнейшие исследования. Следует отметить, что вкДНК также содержит митохондриальную ДНК (вкмтДНК), фрагменты геномов вирусов и бактерий [9][10][11]. Повышение уровня митохондриальной ДНК (мтДНК) в крови обнаружено у женщин c преэклампсией [12][13][14][15][16][17], гестационным сахарным диабетом [18], задержкой развития плода [19].…”

“…Это позволяет рассматривать вкмтДНК в качестве потенциального биомаркера осложнений беременности. В свою очередь вирусные и бактериальные инфекции также могут вызвать осложнения беременности, а их своевременное выявление и лечение позволяет избежать тяжелых последствий [9,11,20].…”

“…Кардиоваскулярная терапия и профилактика. 2023;22 (11):3742. doi:10.15829/1728-8800-2023-3742. EDN GJDCNT *Автор, ответственный за переписку (Corresponding author): e-mail: vi_lena@list.ru [Вашукова Е.…”