Interactions between host and gut microbiota in gestational diabetes mellitus and their impacts on offspring.

Gestational diabetes mellitus (GDM) is characterized by insulin resistance and low-grade inflammation, and most studies have demonstrated gut dysbiosis in GDM pregnancies. Overall, they were manifested as a reduction in microbiome diversity and richness, depleted short chain fatty acid (SCFA)-producing genera and a dominant of Gram-negative pathogens releasing lipopolysaccharide (LPS). The SCFAs functioned as energy substance or signaling molecules to interact with host locally and beyond the gut. LPS contributed to pathophysiology of diseases through activating Toll-like receptor 4 (TLR4) and involved in inflammatory responses. The gut microbiome dysbiosis was not only closely related with GDM, it was also vital to fetal health through vertical transmission. In this review, we summarized gut microbiota signature in GDM pregnancies of each trimester, and presented a brief introduction of microbiome derived SCFAs. We then discussed mechanisms of microbiome-host interactions in the physiopathology of GDM and associated metabolic disorders. Finally, we compared offspring microbiota composition from GDM with that from normal pregnancies, and described the possible mechanism.

Imbalance of gut microbiota in gestational diabetes.

AIM: To investigate the differences in gut microbiota composition among nonpregnant women of reproductive age, healthy pregnant women, and gestational diabetes (GD) patients. METHODS: A total of 45 outpatients were enrolled and divided into three groups: nonpregnant women of reproductive age (control group, n = 23), healthy pregnant women (normal group, n = 10), and GD patients (GD group, n = 12). Faecal samples were collected and sequenced using 16S rRNA gene sequencing to analyse the microbial composition. RESULTS: (1) Pregnant patients exhibited an increase in the abundance of Streptococcus (Pnormal = 0.01286, PGD = 0.002965) and Blautia (Pnormal = 0.0003924, PGD = 0.000246) but a decrease in the abundance of Roseburia (Pnormal = 0.0361, PGD = 0.007075), Phascolarctobacterium (Pnormal = 0.0003906, PGD = 0.02499) and Lachnoclostridium (Pnormal = 0.0003906, PGD = 0.03866). (2) Compared with healthy pregnant women, GD patients had an excessive increase in Streptococcus abundance and decrease in Roseburia abundance. The increase in Blautia abundance and the decrease in Phascolarctobacterium and Lachnoclostridium abundance in GD patients were less than those in healthy pregnant women. (3) The abundance of Faecalibacterium prausnitzii decreased significantly in GD patients (PGD = 0.02985) but not in healthy pregnant patients (Pnormal = 0.1643). CONCLUSIONS: Abnormal increases and decreases in the abundances of gut microbiota components, especially Faecalibacterium prausnitzii, were observed in GD patients. TRIAL REGISTRATION: The cross-sectional research was conducted in accordance with the Declaration of Helsinki, and approved by Sir Run Run Shaw Hospital Clinical Trials and Biomedical Ethics Committee. The study has been registered in the Chinese Clinical Trial Registry (ChiCTR1900026164, 24/09/2019, http://www.chictr.org.cn/showproj.aspx?proj=43,455 ).

Gestational diabetes-related gut microbiome dysbiosis is not influenced by different Asian ethnicities and dietary interventions: a pilot study.

Gut microbiome dysbiosis contributes to the pathophysiology of both gestational diabetes mellitus (GDM) and its associated adverse outcomes in the woman and offspring. Even though GDM prevalence, complications, and outcomes vary among different ethnic groups, limited information is available about the influence of ethnicity on gut microbiome dysbiosis in pregnancies complicated by GDM. This pilot prospective cohort study examined the impact of ethnicity on gut dysbiosis in GDM among three Asian ethnic groups (Chinese, Malay, Indian) living in Singapore, and investigated the potential modulatory roles of diet and lifestyle modifications on gut microbiome post-GDM diagnosis. Women with GDM (n = 53) and without GDM (n = 16) were recruited. Fecal samples were collected at 24-28- and 36-40-weeks' gestation and analyzed by targeted 16S rRNA gene-based amplicon sequencing. Permutational multivariate analysis of variance (PERMANOVA) analysis was performed to evaluate differences between groups. Differentially abundant taxa were identified by DeSeq2 based analysis. Functional prediction was performed using the phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt2). Among women with GDM, gut microbiome from different ethnicities harbored common microbial features. However, among those without GDM, there was contrasting microbiome composition between ethnic groups. Microbial members such as Collinsella, Blautia, Ruminococcus, Ruminococcus gnavus, Ruminococcus torques, and Eubacterium hallii groups were differentially enriched (p < 0.05) in women with GDM compared to those without. Among women with GDM, no differences in alpha- and beta- diversity were observed when comparing 24-28 weeks' samples with 36-40 weeks' samples, a period covering intense dietary and lifestyle modification, suggesting an inability to modulate gut microbiota through classic GDM management. Women with GDM have a distinct gut microbiome profile which harbours common features across different Asian ethnic groups, consistent with the notion that specific microbes are involved in the pathogenesis of insulin resistance, pro-inflammatory conditions, and other metabolic dysregulation known to be present in GDM.

Spatiotemporal patterns of the pregnancy microbiome and links to reproductive disorders.

The microbiome of females undergoes extensive remodeling during pregnancy, which is likely to have an impact on the health of both mothers and offspring. Nevertheless, large-scale integrated investigations characterizing microbiome dynamics across key body habitats are lacking. Here, we performed an extensive meta-analysis that compiles and analyzes microbiome profiles from  >10,000 samples across the gut, vagina, and oral cavity of pregnant women from diverse geographical regions. We have unveiled unexpected variations in the taxonomic, functional, and ecological characteristics of microbial communities throughout the course of pregnancy. The gut microbiota showed distinct trajectories between Western and non-Western populations. The vagina microbiota exhibited fluctuating transitions at the genus level across gestation, while the oral microbiota remained relatively stable. We also identified distinctive microbial signatures associated with prevalent pregnancy-related disorders, including opposite variations in the oral and gut microbiota of patients with gestational diabetes and disrupted microbial networks in preterm birth. This study establishes a comprehensive atlas of the pregnancy microbiome by integrating multidimensional datasets and offers foundational insights into the intricate interplay between microbes and host factors that underlie reproductive health.

Composition of the intestinal microbiota and its variations between the second and third trimesters in women with gestational diabetes mellitus and without gestational diabetes mellitus.

Objective: This study was designed to explore the composition of the intestinal microbiota and its longitudinal variation between the second trimester (T2) and the third trimester (T3) in women with gestational diabetes mellitus (GDM) and pregnant women with normal glucose tolerance. Methods: This observational study was conducted at Peking Union Medical College Hospital (PUMCH). Women with GDM and pregnant women with normal glucose tolerance were enrolled in the study, and fecal samples were collected during T2 (weeks 24~28) and T3 (weeks 34~38). Fecal samples were analyzed from 49 women with GDM and 42 pregnant women with normal glucose tolerance. The 16S rRNA gene amplicon libraries were sequenced to analyze the microbiota and QIIME2 was used to analyze microbiome bioinformatics. Results: The four dominant phyla that Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria which accomplish about 99% of the total relative abundance did not significantly change between the T2 and T3 in the GDM and healthy groups. At the genus level, the relative abundance of Scardovia (0 vs. 0.25%, P = 0.041) and Propionibacterium (0 vs. 0.29%, P = 0.041) increased significantly in the control group, but not in the GDM group. At the phylum level, the relative abundance of Firmicutes and Actinobacteria was significantly different between women with GDM and pregnant women with normal glucose tolerance in both T2 and T3. In T2 and T3, the relative abundances of unidentified_Lachnospiraceae, Blautia, and Parabacteroides were significantly higher in the GDM group than in the control group (P<0.05). The relative abundance of Bifidobacterium in the GDM group was lower than in the control group in both T2 and T3. Conclusions: The intestinal microbiota composition was stable from T2 to T3 in the GDM and control groups; however, the intestinal microbiota composition was different between the two groups.

Association of Gestational Diabetes With the Dynamic Changes of Gut Microbiota in Offspring From 1 to 6 Months of Age.

AIMS: The present study aimed to prospectively evaluate the influence of gestational diabetes mellitus (GDM) on the gut microbiota in 1- and 6-month-old offspring, as well as the dynamic changes from 1 to 6 months of age. METHODS: Seventy-three mother-infant dyads (34 GDM vs 39 non-GDM) were included in this longitudinal study. Two fecal samples were collected for each included infant at home by the parents at 1 month of age ("M1 phase") and again at 6 months of age ("M6 phase"). Gut microbiota were profiled by 16S rRNA gene sequencing. RESULTS: Although no significant differences were observed in diversity and composition between GDM and non-GDM groups in the M1 phase, we observed differential structures and composition in the M6 phase between the 2 groups (P < .05), with lower levels of diversity, 6 depleted and 10 enriched gut microbes among infants born to GDM mothers. The dynamic changes in alpha diversity from the M1 to M6 phase were also significantly different according to GDM status (P < .05). Moreover, we found that the altered gut bacteria in the GDM group were correlated with infants' growth. CONCLUSION: Maternal GDM was associated not only with the community structure and composition in the gut microbiota of offspring at a specific time point, but also with the differential changes from birth to infancy. Altered colonization of the GDM infants' gut microbiota might affect their growth. Our findings underscore the critical impact of GDM on the formation of early-life gut microbiota and on the growth and development of infants.

Integrative metagenomic and metabolomic analyses reveal gut microbiota-derived multiple hits connected to development of gestational diabetes mellitus in humans.

Gestational diabetes mellitus (GDM) is characterized by the development of hyperglycemia and insulin resistance during the second or third trimester of pregnancy, associated with considerable risks to both the mother and developing fetus. Although emerging evidence suggests an association between the altered gut microbiota and GDM, remarkably little is known about the microbial and metabolic mechanisms that link the dysbiosis of the gut microbiota to the development of GDM. In this study, a metagenome-wide association study and serum metabolomics profiling were performed in a cohort of pregnant women with GDM and pregnant women with normal glucose tolerance (NGT). We identified gut microbial alterations associated with GDM and linked to the changes in circulating metabolites. Blood metabolite profiles revealed that GDM patients exhibited a marked increase in 2-hydroxybutyric acid and L-alpha-aminobutyric acid, but a decrease in methionine sulfoxide, allantoin, and dopamine and dopaminergic synapse, when compared with those in NGT controls. Short-chain fatty acid-producing genera, including Faecalibacterium, Prevotella, and Streptococcus, and species Bacteroides coprophilus, Eubacterium siraeum, Faecalibacterium prausnitzii, Prevotella copri, and Prevotella stercorea, were significantly reduced in GDM patients relative to those in NGT controls. Bacterial co-occurrence network analysis revealed that pro-inflammatory bacteria were over-represented as the core species in GDM patients. These microbial and metabolic signatures are closely associated with clinical parameters of glucose metabolism in GDM patients and NGT controls. In conclusion, we identified circulating dopamine insufficiency, imbalanced production of SCFAs, and excessive metabolic inflammation as gut microbiota-driven multiple parallel hits linked to GDM development. This work might explain in part the mechanistic link between altered gut microbiota and GDM pathogenesis, and suggest that gut microbiota may serve as a promising target to intervene in GDM.

Mycobiota composition and changes across pregnancy in patients with gestational diabetes mellitus (GDM).

The gut mycobiota has never been studied either during pregnancy or in patients with gestational diabetes (GDM). This study aimed to analyze the fecal mycobiota of GDM patients during the second (T2) and third (T3) trimester of pregnancy and to compare it with the mycobiota of pregnant normoglycemic women (controls). Forty-one GDM patients and 121 normoglycemic women were studied. GDM mycobiota was composed almost exclusively by the Ascomycota phylum; Basidiomicota accounted for 43% of the relative frequency of the controls. Kluyveromyces (p < 0.001), Metschnikowia (p < 0.001), and Pichia (p < 0.001) showed a significantly higher frequency in GDM patients, while Saccharomyces (p = 0.019), were more prevalent in controls. From T2 to T3, a reduction in fungal alpha diversity was found in GDM patients, with an increase of the relative frequency of Candida, and the reduction of some pro-inflammatory taxa. Many associations between fungi and foods and nutrients were detected. Finally, several fungi and bacteria showed competition or co-occurrence. Patients with GDM showed a predominance of fungal taxa with potential inflammatory effects when compared to normoglycemic pregnant women, with a marked shift in their mycobiota during pregnancy, and complex bacteria-fungi interactions.

Gut microbiota in pregnant Malaysian women: a comparison between trimesters, body mass index and gestational diabetes status.

BACKGROUND: The primary purpose of the study is to determine the variation of gut microbiota composition between first (T1) and third trimester (T3); gestational diabetes mellitus (GDM) and non-gestational diabetes mellitus (NGDM); and also within a different category of Body Mass Index (BMI) of selected pregnant Malaysian women. METHODS: A prospective observational study on selected 38 pregnant Malaysian women attending a tertiary medical centre was carried out. Those with preexisting diabetes, metabolic syndrome or any other endocrine disorders were excluded. GDM was determined using oral glucose tolerance test (OGTT) while BMI was stratified as underweight, normal, pre-obese and obese. Fecal samples were then collected during the first trimester (T1) and the third trimester (T3). The V3-V4 region of 16S rRNA gene amplicon libraries were sequenced and analyzed using QIIME (version 1.9.1) and METAGENassist. RESULTS: Twelve women (31.6%) were diagnosed as GDM. A trend of lower α-diversity indices in GDM, pre-obese and obese pregnant women were observed. Partial Least Squares Discriminant Analysis (PLS-DA) shows a clustering of gut microbiota according to GDM status and BMI, but not by trimester. Genera Acidaminococcus, Clostridium, Megasphaera and Allisonella were higher, and Barnesiella and Blautia were lower in GDM group (P < 0.005). Obese patients had gut microbiota that was enriched with bacteria of Negativicutes and Proteobacteria class such as Megamonas, Succinatimonas and Dialister (P < 0.005). The normal and mild underweight profiles on the other hand had a higher bacteria from the class of Clostridia (Papillibacter, Oscillibacter, Oscillospira, Blautia, Dorea) and Bacteroidia (Alistipes, Prevotella, Paraprevotella) (P < 0.005). CONCLUSION: The prevalence and variation of several key bacteria from classes of Negativicutes, Clostridia and Proteobacteria has potential metabolic links with GDM and body weight during pregnancy which require further functional validation.

Epigenetic Links between Microbiota and Gestational Diabetes.

Gestational diabetes mellitus (GDM) is considered a significant and increasing worldwide problem. The growing body of evidence on this topic has allowed us to point out that a hostile intrauterine environment in mothers with GDM via epigenetic mechanisms induces "diabetogenic" and "obesogenic" changes in an offspring's DNA. This sets a vicious intergenerational cycle of metabolic diseases in motion, gradually deteriorating the health of the human population. One of the most important participants of this process seems to be altered microbiota. There is a chance that the identification of specific epigenetic marks may provide a key for future diagnostic, prognostic and therapeutic solutions in the field of personalised medicine. Given the reversibility of most epigenetic changes, there is an opportunity to improve the long-term health of the human population. In this manuscript, we aim to summarise available data on epigenetic changes among women suffering from GDM and their progeny, in association with alterations in the microbiome.

Characteristics of the gut microbiome in women with gestational diabetes mellitus: A systematic review.

BACKGROUND: The incidence of women developing gestational diabetes mellitus (GDM) is increasing, which is associated with an increased risk of type 2 diabetes mellitus (T2DM) for both mother and child. Gut microbiota dysbiosis may contribute to the pathogenesis of both GDM and the accompanying risk of T2DM. Thus, a better understanding of the microbial communities associated with GDM could offer a potential target for intervention and treatment in the future. Therefore, we performed a systematic review to investigate if the GDM women have a distinct gut microbiota composition compared to non-GDM women. METHODS: We identified 21 studies in a systematic literature search of Embase and PubMed up to February 24, 2021. Data on demographics, methodology and identified microbial metrics were extracted. The quality of each study was assessed according to the Newcastle-Ottawa Scale. RESULTS: Sixteen of the studies did find a GDM-associated gut microbiota, although no consistency could be seen. Only Collinsella and Blautia showed a tendency to be increased in GDM women, whereas the remaining genera were significantly different in opposing directions. CONCLUSION: Although most of the studies found an association between GDM and gut microbiota dysbiosis, no overall GDM-specific gut microbiota could be identified. All studies in the second trimester found a difference between GDM and non-GDM women, indicating that dysbiosis is present at the time of diagnosis. Nevertheless, it is still unclear when the dysbiosis develops, as no consensus could be seen between the studies investigating the gut microbiota in the first trimester of pregnancy. However, studies varied widely concerning methodology and study design, which might explain the highly heterogeneous gut microbiota compositions between studies. Therefore, future studies need to include multiple time points and consider possible confounding factors such as ethnicity, pre-pregnancy body mass index, and GDM treatment.

16S rRNA gene amplicon sequencing of gut microbiota in gestational diabetes mellitus and their correlation with disease risk factors.

PURPOSE: Although the gut microbiota (GM) are associated with various diseases, their role in gestational diabetes mellitus (GDM) remains uncharacterized. Further study is urgently needed to expose the real relationship between GM and GDM. METHODS: We performed a prospective study in 33 pregnant Chinese individuals [15, GDM; 18, normal glucose tolerance (NGT)] to observe the fecal microbiota by 16S rRNA gene amplicon sequencing at 24-28 weeks of gestational age after a standard 75 g oral glucose tolerance test. Linear regression analysis was employed to assess the relationships between the GM and GDM clinical parameters. RESULTS: Sequencing showed no difference in the microbiota alpha diversity but a significant difference in the beta diversity between the GDM and NGT groups, with the relative abundances of Ruminococcus bromii, Clostridium colinum, and Streptococcus infantis being higher in the GDM group (P < 0.05). The quantitative PCR results validated the putative bacterial markers of R. bromii and S. infantis. Moreover, a strong positive correlation was found between S. infantis and blood glucose levels after adjusting for body mass index (P < 0.05). CONCLUSION: Three abnormally expressed intestinal bacteria (R. bromii, C. colinum, and S. infantis) were identified in GDM patients. S. infantis may confer an increased risk of GDM. Hence, the GM may serve as a potential therapeutic target for GDM.

Differential analysis of the bacterial community in colostrum samples from women with gestational diabetes mellitus and obesity.

Gestational Diabetes Mellitus (GDM) and obesity affect the functioning of multiple maternal systems and influence colonization of the newborn gastrointestinal through the breastmilk microbiota (BMM). It is currently unclear how GDM and obesity affect the human BMM composition. Here, we applied 16S-rRNA high-throughput sequencing to human colostrum milk to characterize BMM taxonomic changes in a cohort of 43 individuals classified in six subgroups according to mothers patho-physiological conditions (healthy control (n = 18), GDM (n = 13), or obesity (n = 12)) and newborn gender. Using various diversity indicators, including Shannon/Faith phylogenetic index and UniFrac/robust Aitchison distances, we evidenced that BMM composition was influenced by the infant gender in the obesity subgroup. In addition, the GDM group presented higher microbial diversity compared to the control group. Staphylococcus, Corynebacterium 1, Anaerococcus and Prevotella were overrepresented in colostrum from women with either obesity or GDM, compared to control samples. Finally, Rhodobacteraceae was distinct for GDM and 5 families (Bdellovibrionaceae, Halomonadaceae, Shewanellaceae, Saccharimonadales and Vibrionaceae) were distinct for obesity subgroups with an absolute effect size greater than 1 and a q-value ≤ 0.05. This study represents the first effort to describe the impact of maternal GDM and obesity on BMM.

Periodontitis and Gestational Diabetes Mellitus: A Potential Inflammatory Vicious Cycle.

Periodontitis is a chronic inflammatory immune disease associated with a dysbiotic state, influenced by keystone bacterial species responsible for disrupting the periodontal tissue homeostasis. Furthermore, the severity of periodontitis is determined by the interaction between the immune cell response in front of periodontitis-associated species, which leads to the destruction of supporting periodontal tissues and tooth loss in a susceptible host. The persistent bacterial challenge induces modifications in the permeability and ulceration of the sulcular epithelium, which facilitates the systemic translocation of periodontitis-associated bacteria into distant tissues and organs. This stimulates the secretion of pro-inflammatory molecules and a chronic activation of immune cells, contributing to a systemic pro-inflammatory status that has been linked with a higher risk of several systemic diseases, such as type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM). Although periodontitis and GDM share the common feature of systemic inflammation, the molecular mechanistic link of this association has not been completely clarified. This review aims to examine the potential biological mechanisms involved in the association between periodontitis and GDM, highlighting the contribution of both diseases to systemic inflammation and the role of new molecular participants, such as extracellular vesicles and non-coding RNAs, which could act as novel molecular intercellular linkers between periodontal and placental tissues.

Early gut dysbiosis could be an indicator of unsuccessful diet control in gestational diabetes mellitus.

Highlights At the time of gestational diabetes mellitus (GDM) diagnosis, gut dysbiosis was severer in mothers who ended up with diet control failure than those who ended up with successful diet control. This finding was noticed even when the glycemic profile at the time of GDM diagnosis was similar between these two groups. Interestingly, gut dysbiosis in GDM mothers with diet control failure was shown associated with gut dysbiosis in their newborns.

Probiotic supplements alleviate gestational diabetes mellitus by restoring the diversity of gut microbiota: a study based on 16S rRNA sequencing.

Probiotics effectively prevent and improve metabolic diseases such as diabetes by regulating the intestinal microenvironment and gut microbiota. However, the effects of probiotics in gestational diabetes mellitus are not clear. Here, we showed that probiotic supplements significantly improved fasting blood glucose in a gestational diabetes mellitus rat model. To further understand the mechanisms of probiotics in gestational diabetes mellitus, the gut microbiota were analyzed via 16S rRNA sequencing. We found that compared with the normal pregnant group, the gestational diabetes mellitus rats had decreased diversity of gut microbiota. Moreover, probiotic supplementation restored the diversity of the gut microbiota in gestational diabetes mellitus rats, and the gut microbiota structure tended to be similar to that of normal pregnant rats. In particular, compared with gestational diabetes mellitus rats, the abundance of Firmicutes and Actinobacteria was higher after probiotic supplementation. Furthermore, activating carbohydrate metabolism and membrane transport pathways may be involved in the potential mechanisms by which probiotic supplements alleviate gestational diabetes mellitus. Overall, our results suggested that probiotic supplementation might be a novel approach to restore the gut microbiota of gestational diabetes mellitus rats and provided an experimental evidence for the use of probiotic supplements to treat gestational diabetes mellitus.

Maternal gut microbiota displays minor changes in overweight and obese women with GDM.

BACKGROUND AND AIMS: Previous literature have shown a diversity of findings regarding the relationship between the maternal gut microbiota and gestational diabetes mellitus (GDM). We investigated the gut microbiota of overweight and obese women with gestational diabetes mellitus (GDM) against matched euglycaemic women at 16 and 28-weeks' gestation. METHODS AND RESULTS: This study included women from the SPRING (Study of PRobiotics IN Gestational diabetes) cohort. Overweight and obese women with no impaired glucose tolerance or impaired fasted glucose were enrolled prior to gestational age <16 weeks. Participants with a diagnosis of GDM (n = 29) were matched with euglycaemic (n = 29) women for body mass index, probiotic or placebo intervention, maternal age, parity and ethnicity. Anthropometric, clinical and fecal microbiota (16S rRNA amplicon-based sequencing of V6-V8 region) data was assessed at 16 and 28-weeks' gestation. The relative abundances of key bacterial genera were not significantly altered between euglycaemic women and women with GDM. Occurrence of bacterial taxa was similar between groups at both timepoints. GDM was associated with decreased Shannon diversity (p = 0.02) without differentiated clustering measured by beta diversity at 28-weeks' gestation. CONCLUSIONS: Overweight and obese women with GDM demonstrate minor variation in the gut microbiota at 16 and 28-weeks' gestation compared with matched euglycaemic women. This study expands on previous literature concluding the microbiota does not likely have a disease-specific characterisation in GDM.

Application of methane and hydrogen-based breath test in the study of gestational diabetes mellitus and intestinal microbes.

OBJECTIVE: Gestational diabetes mellitus (GDM) is a common complication of pregnancy. The purpose of this study was to compare the incidence of small intestinal bacterial overgrowth (SIBO) in patients with GDM and the control group by methane and hydrogen lactulose breath test (LBT), and to explore its relationship with inflammation, vitamins, and the outcomes of maternal and child. METHODS: LBT was detected in 220 GDM patients, 160 pregnancy control patients and 160 pre-pregnancy control patients. The fasting blood glucose, white blood cells, vitamin A, D, E, neonatal weight, neonatal blood glucose and so on were compared and analyzed. RESULTS: There was no statistical significance in the general data of the three groups. The proportion of abdominal distension in the GDM group was higher than that in the other two groups (P < 0.001). The positive rates of SIBO + in GDM group, gestational control group and pre-pregnancy control group were 54.55%, 27.50% and 14.38%, respectively. The average abundance of hydrogen and methane in GDM group was significantly higher than that in control group at each time point. In the GDM group, SIBO + subjects had higher levels of fasting blood glucose, glycoglycated hemoglobin, C-reactive protein, neonatal weight, and lower levels of vitamin D and neonatal blood glucose (P < 0.001). CONCLUSION: Patients with GDM have a high incidence of SIBO, and SIBO may further increase their blood glucose by affecting inflammatory response and vitamin level, and even affect the outcome of mother and child.

Association of gestational diabetes mellitus with changes in gut microbiota composition at the species level.

BACKGROUND: Gestational diabetes mellitus (GDM), a common endocrine disorder with rising prevalence in pregnancy, has been reported to be associated with alteration of gut microbiota in recent years. However, the role of gut microbiome in GDM physiopathology remains unclear. This pilot study aims to characterize the alteration of gut microbiota in GDM on species-level resolution and evaluate the relationship with occurrence of GDM. METHODS: An analysis based on 16S rRNA microarray was performed on fecal samples obtained from 30 women with GDM and 28 healthy pregnant women. RESULTS: We found 54 and 141 differentially abundant taxa between GDM and control group at the genus and the species level respectively. Among GDM patients, Peptostreptococcus anaerobius was inversely correlated with fasting glucose while certain species (e.g., Aureimonas altamirensis, Kosakonia cowanii) were positively correlated with fasting glucose. CONCLUSIONS: This study suggests that there are large amounts of differentially abundant taxa between GDM and control group at the genus and the species level. Some of these taxa were correlated with blood glucose level and might be used as biomarkers for diagnoses and therapeutic targets for probiotics or synbiotics.

Association of Gut Microbiota during Early Pregnancy with Risk of Incident Gestational Diabetes Mellitus.

AIMS: We aimed to assess the association between gut bacterial biomarkers during early pregnancy and subsequent risk of gestational diabetes mellitus (GDM) in Chinese pregnant women. METHODS: Within the Tongji-Shuangliu Birth Cohort study, we conducted a nested case-control study among 201 incident GDM cases and 201 matched controls. Fecal samples were collected during early pregnancy (at 6-15 weeks), and GDM was diagnosed at 24 to 28 weeks of pregnancy. Community DNA isolated from fecal samples and V3-V4 region of 16S rRNA gene amplicon libraries were sequenced. RESULTS: In GDM cases versus controls, Rothia, Actinomyces, Bifidobacterium, Adlercreutzia, and Coriobacteriaceae and Lachnospiraceae spp. were significantly reduced, while Enterobacteriaceae, Ruminococcaceae spp., and Veillonellaceae were overrepresented. In addition, the abundance of Staphylococcus relative to Clostridium, Roseburia, and Coriobacteriaceae as reference microorganisms were positively correlated with fasting blood glucose, 1-hour and 2-hour postprandial glucose levels. Adding microbial taxa to the base GDM prediction model with conventional risk factors increased the C-statistic significantly (P < 0.001) from 0.69 to 0.75. CONCLUSIONS: Gut microbiota during early pregnancy was associated with subsequent risk of GDM. Several beneficial and commensal gut microorganisms showed inverse relations with incident GDM, while opportunistic pathogenic members were related to higher risk of incident GDM and positively correlated with glucose levels on OGTT.