Gut microbiota dysbiosis, circulating microbial genetic traces, and their role in gestational diabetes

Table 1 Summary of key human studies investigating gut microbiota dysbiosis and circulating microbial DNA in relation to gestational diabetes mellitus[4,55-66]

No.	Citation	Year	Country	Design	Gut microbiota assessed	Circulating cfDNA assessed	Sequencing Methodology	Contamination controls	Antibiotics reported/controlled	Longitudinal	Key findings	Limitations
1	Gomez-Arango et al[55]	2016	Australia	Cross-sectional; overweight/obese pregnant women; n = 70	Yes (fecal 16S)	No	16S rRNA (Illumina)	Not reported	Not reported	No	Collinsella associated with insulin; gut taxa correlate with metabolic hormones	Small sample, overweight/obese cohort, no cfDNA data
2	Crusell et al[4]	2018	Denmark	Case-control and longitudinal postpartum; GDM n = 50, controls n = 157	Yes (fecal 16S + metagenomics)	No	16S rRNA/shotgun (variable)	Not clearly stated	Not reported	Yes (postpartum)	GDM associated with altered fecal microbiota (Collinsella, Rothia, Desulfovibrio)	Heterogeneous methods, observational
3	Ferrocino et al[56]	2018	Italy	Prospective observational; GDM n = 41, controls	Yes (fecal 16S)	No	16S rRNA	Not reported	Not reported	Yes (pregnancy)	Microbiota changes during pregnancy in GDM; links to diet and metabolic markers	Small sample, observational
4	Pinto et al[57]	2023	United Kingdom/Israel (multi-centre)	Prospective cohort; early sampling before GDM diagnosis; sizeable cohort (development and validation)	Yes (multi-omics fecal)	No	16S/shotgun metagenomics, metabolomics	Reported (standard pipelines)	Partially reported	Yes (samples months before diagnosis)	Microbiota-induced inflammation precedes GDM; decreased fecal SCFAs in those who developed GDM	Requires mechanistic validation
5	Hu et al[58]	2021	China	Prospective cohort; early pregnancy sampling; moderate N	Yes	No	16S rRNA	Not reported	Not reported	Yes	Early pregnancy gut microbiota associated with later GDM risk	Needs replication in other populations
6	Witt et al[59]	2020	United States	Case-control; chorioamnionitis cases vs controls; small N	No	Yes (mcfDNA sequencing in maternal plasma)	Shotgun cfDNA sequencing (NGS)	Described (negative controls)	Not central to study	No	mcfDNA detected in maternal and cord plasma in chorioamnionitis; higher levels vs controls	Not GDM-focused; small sample
7	Tang et al[60]	2024	China/International	Longitudinal cfDNA study; GDM n = 299, controls n = 299	Partially (integrative analyses)	Yes (deep cfDNA sequencing)	High-depth cfDNA sequencing (Illumina)	Reported (bioinformatic filters)	Not fully reported	Yes	cfDNA fragment features associated with GDM across pregnancy; potential predictive signals	Needs external replication; novel methods
8	Wang et al[61]	2023	China	Large cohort (n > 5000), cfDNA sequencing data for GDM prediction	No	Yes (cfDNA features)	NIPT-style cfDNA sequencing	Not fully described in abstract	Not reported	No (screening dataset)	Machine learning on cfDNA can screen/predict GDM	Early; requires independent validation and contamination-aware analysis
9	Su et al[62]	2021	China	Case-control; GDM vs controls; small N	Yes (fecal 16S)	No	16S rRNA	Not reported	Not reported	No	Distinct gut microbiota signatures in GDM	Cross-sectional; small sample
10	Liu et al[63]	2019	China	Case-control/prospective; moderate N	Yes (fecal metagenomics)	No	Shotgun metagenomics	Not reported	Not reported	Some follow-up	Fecal microbiota linked to plasma lipidome and GDM risk	Causality not established
11	Zheng et al[64]	2020	China	Prospective; first half of pregnancy; sample size moderate	Yes (16S)	No	16S rRNA	Not reported	Not reported	Yes	Reduced dynamics of gut microbiota during early pregnancy associated with GDM	Population-specific; replication needed
12	Ma et al[65]	2020	China	Cross-sectional; first trimester	Yes	No	16S rRNA	Not reported	Not reported	No	Altered early pregnancy microbiota in GDM patients	Small; cross-sectional
13	Ponzo et al[66]	2019	Italy	Associated with Ferrocino dataset; maternal and offspring microbiome studies	Yes	No	16S rRNA	Not reported	Not reported	Yes (infant follow-up)	Offspring microbiota influenced by maternal GDM	Cohort-specific

The table includes study characteristics, methodologies, and major findings. cfDNA: Circulating free DNA; GDM: Gestational diabetes mellitus; mcfDNA: Microbial cell-free DNA; NGS: Next-generation sequencing; NIPT: Non-invasive prenatal testing; SCFA: Short-chain fatty acid.