Type 1 diabetes in pregnancy is associated with distinct changes in the composition and function of the gut microbiome.

BACKGROUND: The gut microbiome changes in response to a range of environmental conditions, life events and disease states. Pregnancy is a natural life event that involves major physiological adaptation yet studies of the microbiome in pregnancy are limited and their findings inconsistent. Pregnancy with type 1 diabetes (T1D) is associated with increased maternal and fetal risks but the gut microbiome in this context has not been characterized. By whole metagenome sequencing (WMS), we defined the taxonomic composition and function of the gut bacterial microbiome across 70 pregnancies, 36 in women with T1D. RESULTS: Women with and without T1D exhibited compositional and functional changes in the gut microbiome across pregnancy. Profiles in women with T1D were distinct, with an increase in bacteria that produce lipopolysaccharides and a decrease in those that produce short-chain fatty acids, especially in the third trimester. In addition, women with T1D had elevated concentrations of fecal calprotectin, a marker of intestinal inflammation, and serum intestinal fatty acid-binding protein (I-FABP), a marker of intestinal epithelial damage. CONCLUSIONS: Women with T1D exhibit a shift towards a more pro-inflammatory gut microbiome during pregnancy, associated with evidence of intestinal inflammation. These changes could contribute to the increased risk of pregnancy complications in women with T1D and are potentially modifiable by dietary means. Video abstract.

Asymptomatic bacteriuria and urinary tract infection in pregnant women with and without diabetes: Cohort study.

OBJECTIVE: To compare the prevalence of asymptomatic bacteriuria (ASB) and the incidence of urinary tract infection (UTI) in pregnant women with and without diabetes mellitus (DM) or gestational DM (GDM). STUDY DESIGN: We performed a cohort study in five hospitals and two midwifery clinics in the Netherlands. Pregnant women with and without DM or GDM were screened for the presence of ASB around 12 and 32 weeks' gestation. Characteristics of participants as well as outcome data were collected from questionnaires and medical records. ASB was defined as the growth of at least 10e5 cfu/ml isolated from the urine of a woman without UTI complaints. UTI was considered to be present when a treating physician had diagnosed UTI and prescribed antibiotics. RESULTS: We studied 202 women with and 272 women without DM or GDM. Of all women 31.7% with and 94.9% without DM or GDM provided a week 12 sample. The prevalence of ASB was comparable in women with and without DM or GDM (12 weeks' n = 322; 4.7% and 2.3%; relative risk (RR) 2.02; 95% confidence interval (CI) 0.52-7.84; 32 weeks' n = 422; 3.2% and 3.0%; RR 1.06; 95% CI 0.36-3.09), as was the incidence of UTI (16.8% and 12.9%; RR 1.31; 95% CI 0.85-2.02). Neither ASB nor UTI were associated with preterm birth or babies being small for gestational age. CONCLUSION: In pregnant women with and women without DM or GDM, the overall prevalence of ASB was low. Neither ASB nor UTI did differ significantly between the groups. Our data discourage a routine ASB screen and treat policy in pregnant women with DM or GDM.

Cervicovaginal bacteria and fungi in pregnant diabetic and non-diabetic women: a multicenter observational cohort study.

OBJECTIVE: We evaluated the prevalence of cervicovaginal Bacteria, group B Streptococcus (GBS), Gardnerella vaginalis (GV), Candida spp., Chlamydia trachomatis (CT), Mycoplasma hominis (MH) and Ureaplasma urealyticum (UU) in pregnant women with and without diabetes mellitus (DM). PATIENTS AND METHODS: Cervicovaginal swabs were gathered from 473 pregnant patients divided into 127 diabetic and 346 non-diabetic. The results were correlated to gestational age, parity and glycemic control. RESULTS: A higher prevalence of MH/UU (p=0.012) was found in the diabetic patients. After the 28th week of pregnancy, the prevalence for all investigated microorganisms appeared similar except for MH/UU (p=0.014). In multigravida, there were statistical differences between two groups in testing for Bacteria (p=0.015) and for MH/UU (p=0.037). The diabetic condition correlated to the state of multigravida in cases positive for Candida spp. (p=0.049) and in those testing positive for at least one microorganism (p=0.043). Pregnant with a blood glucose > 92 have twice the risk of being positive to a single microbiological test than those with better glycemic control. CONCLUSIONS: The higher prevalence of MH/UU after the 28th weeks can be explained with the physiologically reduced insulin tolerance characteristic of this gestational period. Among the diabetic testing positive to Candida spp. the statistically significant association was observed only in multigravida condition. These data suggest that diabetic multigravida women are at increased risk for Candida spp. infection in relation to the improper glycemic control.

Characterization of the vaginal fungal flora in pregnant diabetic women by 18S rRNA sequencing.

Pregnancy and diabetes are regarded as individual risk factors for vaginal candidiasis. The high prevalence of vaginal candidiasis in pregnant diabetic women can be explained by disruption of the balance of the vaginal normal flora. However, little is known about the overall structure and composition of the vaginal fungal flora in pregnant diabetic women. In the present study, the diversity and richness of the vaginal fungal flora in healthy non-pregnant women (group HN), healthy pregnant women (group HP), women with gestational diabetes mellitus (group GDM), and pregnant women with diabetes mellitus type I (group T1DM) were investigated using an 18S rRNA gene clone library method. Our data demonstrated that the composition of the vaginal fungal flora in the four groups could be divided into two phyla (Ascomycetes, 20/26, and Basidiomycetes, 6/26). The most predominant vaginal fungal species belonged to the Candida and Saccharomyces genera, uncultured fungi, and a large number of low-abundance taxa that were unrecorded or underrepresented in previous studies using cultivation-dependent methods. Variation in operational taxonomic units (OTUs) between the study cohorts was generally high in the clone libraries, as 9, 13, 17, and 20 phylotypes were identified in groups HN, HP, GDM, and T1DM, respectively. The Shannon indices of groups GDM and T1DM (with poorer glycemic control) were significantly higher compared to groups HN and HP (p < 0.05). The data presented here revealed an increased diversity and varied composition of the vaginal fungal flora in pregnant diabetic women and demonstrated that poor glycemic control might be associated with disturbances in the vaginal fungal flora.

[Occurrence of fungal infections in pregnant women and non-pregnant women with diabetes and without diabetes]. / Czestosc wystepowania zarazen grzybami u kobiet ciezarnych i nieciezarnych z cukrzyca i bez cukrzycy.

UNLABELLED: Diabetes and pregnancy are thought to be independent factors increasing the risk of fungal infections. OBJECTIVES: The aim of the study was to evaluate the occurrence of fungal infection of the vagina, rectum and oral cavity in pregnant and non-pregnant women with and without diabetes. MATERIAL AND METHODS: 627 women were included in the study, among them healthy non-pregnant women (HN), healthy pregnant women (HP), pregnant women with diabetes (PD) and non-pregnant women with diabetes (ND). In total, 1881 samples obtained from the vagina, rectum and oral cavity were tested. For species identification API 20 C i API C AUX tests were used. RESULTS: Fungi in at least one locus were detected in 62.4% of all women, among them in 69.8% of HN, 58.5% of HP, 62.5% of PD and 62.7% of ND. Strains were isolated from vaginal samples of HP (16%) less often than in HN (27%) (95% CI 0.29-0.85; OR = 0.5); in ND (31%) and PD (25%) there were no differences in the occurrence of fungi in the vagina (95% CI 0.37-1.38; OR = 0.71). Similar rates of prevalence of fungi in rectum were found in HN (30%) and HP (23%) (95% CI 0.43-1.16; OR = 0.7) as well as in ND (27%) and PD (24%) (95% CI 0.41-1.64; OR = 0.82). Strains have been isolated from oral cavity of 57% of HN and 54% of HP (95% CI 0.58-1.42; OR = 0.9) as well as from 55% ND and 59% of PD (95% CI 0.65-2.21; OR = 1.2). CONCLUSIONS: Lower prevalence of fungi in the vagina of HP, in comparison to HN, suggests a protective effect of pregnancy on the risk of vaginal mycosis. Pregnancy and diabetes independently have no influence on the prevalence of fungi in oral cavity and rectum.

Activity of hydrolytic enzymes in fungi isolated from diabetic pregnant women: is there any relationship between fungal alkaline and acid phosphatase activity and glycemic control?

Ability to respond to environmental changes and secretion of hydrolases are considered to be important for Candida virulence. In this study we determined and compared the activities of 19 different hydrolases of the fungal strains isolated from diabetic and non-diabetic pregnant women. We also looked for the presence of a relationship between hydrolase activities and glycemic control, and, furthermore, evaluated the influence of gestational age on the activity of hydrolases. Mycological examinations were performed for 119 diabetic pregnant women: 47 with diabetes mellitus type I (DM), 72 with gestational diabetes (GDM), and for 132 healthy women (CON). Samples were collected from the vagina, rectum and oral cavity and cultured on Sabouraud media. The fungal hydrolase activities were evaluated using the API ZYM test (bioMerieux). For the 19 different fungal hydrolases tested, 13 activities were present in the isolated fungal strains. The activity of alkaline phosphatase (ALP) in vaginal strains (p=0.028) and acid phosphatase (ACP) in strains from the vagina (p=0.006) and rectum (p=0.049) was significantly lower in DM than in GDM and CON women. In conclusion, we describe for the first time that fungi isolated from pregnant diabetic women have lower activity of both phosphatases compared to fungi isolated from healthy women. Furthermore, similar differences of mean ALP and ACP activities were observed in the course of pregnancy in strains from the vagina and rectum of DM and CON women. However, strains from DM had lower activity at each stage of pregnancy. The highest activity of ALP and ACP was detected at the beginning, then declined, and had the lowest values between the 24(th) and 33(rd) week of gestation. After that period the activity of both phosphatases increased.

Species distribution and influence of glycemic control on fungal infections in pregnant women with diabetes.

OBJECTIVES: (1) To find the distribution of species among fungal strains isolated from pregnant women with diabetes mellitus (DM), gestational diabetes (GDM) and healthy controls (CON); (2) to analyse the influence of glycemia on the prevalence of fungi in different body sites. METHODS: Mycological examinations were performed in 251 pregnant women: 119 diabetic (47 DM, and 72 GDM) and 132 controls. Samples were collected from vagina, rectum and oral cavity of all women and cultured on Sabouraud media. RESULTS: A total of 212 fungal strains were isolated, 12 fungal species were identified: 89.6% of the strains belonged to Candida gender, 10.4% to Saccharomyces, Geotrichum, Rhodotorula and Trichosporon genera. The prevalence of fungi, respectively, in vagina and rectum, was significantly higher in diabetics with poor glycemic control when stratified (<100 mg/dl, 100-120 mg/dl and >120 mg/dl) both the mean week glucose levels (MWGL) levels (p = 0.03, p = 0.03) and glycemia 90 min after breakfast (p = 0.04, 0.03). No difference was found in the prevalence of fungi and glycolised hemoglobin (HbA1). CONCLUSIONS: MWGL showed an association between glycemia and prevalence of fungi. However, no relation was found between HbA1 and fungal infections in well controlled diabetic pregnancies.

[Urinary tract infections in diabetic pregnancy]. / Zakazenia dróg moczowych w ciazy powiklanej cukrzyca.

The analysis of urine culture was performed twice in 120 pregnant women with diabetes mellitus: on their first visit and during the 3rd trimester of pregnancy. During the first evaluation 10% of patients had germ-free culture, 46.7% non-significant bacteriuria and 43.3% significant ones. The percentage of results in the studied group indicating significant bacteriuria decreased as far as to 35.8%, but germ-free culture were still 10% during the second analyses, in 3rd trimester. The incorrect urine culture decreasing count during pregnancy stood in relation with better diabetes control based on 24-hours glucose profile. Staphylococcus and Escherichia coli culture occurred more frequently. The control group comprised of 60 pregnant women without diabetes mellitus-significant bacteriuria occurred in 15% and germ-free culture were observed in 43.4% of patients.

Influence of diabetes on group B Streptococcus colonization in the pregnant patient.

To compare the incidence of group B Streptococcus colonization in diabetic (n = 98) and nondiabetic (n = 10) patients, 199 pregnant women were cultured at the vaginal introitus using a standardised technique. Eight diabetic patients had positive findings for group B Streptococcus cultures, and three nondiabetic patients had positive cultures. No significant difference (P = .109) was found in the group B Streptococcus colonization rates between these two groups of patients. In addition, no significant difference was found in the group B Streptococcal colonization rates between gestational and pregestational diabetics (P = .498). A within-group comparison of diabetic patients revealed that ethnicity (Hispanics versus nonhispanics) did generate a significant difference in the rate of colonization (P = .033). The results of the present study suggest that there is no substantial evidence to consider diabetes mellitus as a higher risk criterion for group B Streptococcus screening. However, population differences and ethnicity should be noted as important contributing factors when considering the implementation of group B Streptococcus screening protocols for pregnant women.

Group B streptococcus colonization in pregnant diabetic women.

OBJECTIVE: To evaluate the influence of maternal diabetes on the risk of group B streptococcus colonization during pregnancy. METHODS: We prospectively analyzed data on 105 pregnant women with diabetes mellitus, both pregestational and gestational, and a control group of 300 pregnant women without carbohydrate intolerance. All had singleton gestations, negative tests for human immunodeficiency virus, and intact membranes at enrollment. Culture specimens for group B streptococcus were obtained from the lower vaginal walls and rectum. Two-tailed unpaired Student t test, Mann-Whitney U test, and chi 2 test were used as appropriate. Multiple logistic regression analyses were performed to evaluate the independent influence of maternal diabetes on the rate of group B streptococcus colonization. RESULTS: Compared to controls, diabetic women had a higher colonization rate (43.8 versus 22.7%, odds ratio [OR] 2.56, 95% confidence interval [CI] 1.6, 4.1). The prevalence of group B streptococcus colonization in pregestational diabetic women was 54.1% and in women with gestational diabetes it was 35.1% (P = .05). Among women with pregestational diabetes, the prevalence of group B streptococcus colonization was 59.1% in class B and 50.0% in class C to R (P = not significant). After we adjusted for maternal age, race, and obesity, diabetic women continued to be at increased risk of group B streptococcus colonization (OR 3.1, 95% CI 1.8, 5.2). CONCLUSION: Carbohydrate intolerance appears to be an independent risk factor for group B streptococcus colonization during pregnancy.

Group B streptococcal colonization in the diabetic gravida patient.

Previous reports have suggested that pregnant diabetic patients have higher carriage rates of group B Streptococcus (GBS) than nondiabetic gravidas. In order to evaluate this in our population, we cultured the posterior pharynx, endocervix, vagina, and rectum of 101 diabetic pregnant women and 100 nondiabetic gravida patients. The colonization rate of GBS was higher in the diabetic population, 31.7%, than in the nondiabetic group 19.0%, (p < 0.039). The vagina was the site most often positive in both diabetic and nondiabetic populations (23.8% and 17.0%, respectively, p = NS). The second site to culture positive overall and the only individual site that was positive significantly more often in diabetics was the rectum (16.9% versus 7.0%, p < 0.05). Differences in colonization rates were not evident when insulin requirement and diabetic classes were considered.

Needle and catheter colonization in pregnant diabetic patients using the continuous subcutaneous insulin infusion pump.

The incidence of bacterial colonization and risk of infection associated with the use of continuous insulin infusion pump (CIIP) was examined in 11 pregnant diabetic patients. All patients received instruction on specific aspects of CIIP and needle insertion technique according to the protocol used in our institution. A total of 220 cultures was performed on the subcutaneous needle and connective tubing. There was no clinical evidence of infection. In conclusion, the risk of infectious cutaneous complications in the pregnant diabetic patient using CIIP is not increased over the nonpregnant diabetic population.

Correlative relationship between adherence of Candida albicans to human vaginal epithelial cells in vitro and candidal vaginitis.

This study investigated whether a correlation exists between predisposition to candidal vaginitis and adherence of Candida albicans to vaginal epithelial cells in vitro. Vaginal epithelial cells from 120 fecund women who were pregnant and/or diabetic had a greater propensity to bind C. albicans than did 71 oral contraceptive users and 75 non-pregnant, non-diabetic controls. The highest level of adherence occurred in pregnant diabetic women. Among 48 non-diabetic postmenopausal females, C. albicans adherence was lower than for fecund controls, but it was higher for cells from 33 postmenopausal diabetic women. The hormonal status of the fecund and postmenopausal women was assayed cytologically by the Karyopyknotic and Maturation Indices, which determine the ratios of superficial, intermediate and parabasal vaginal epithelial cells. Our findings point to increased C. albicans adherence in situations where there is an increase in the number of intermediate epithelial cells: pregnancy, the first or fourth weeks of the menstrual cycle, or diabetes. The adherence of 41 C. albicans isolates from patients with vaginitis was significantly higher than that of 36 isolates from asymptomatic carriers.

PIP: An attempt to determine whether a correlation exists between predisposition to candidal vaginitis and adherence of Candida albicans to vaginal epithelial cells in vitro is reported. Vaginal epithelial cells from 120 fecund women who were pregnant and/or diabetic had a greater propensity to bind C. albicans than did 71 oral contraceptive users and 75 nonpregnant, nondiabetic controls. The highest level of adherence occurred in pregnant diabetic women. Among 48 nondiabetic postmenopausal females, C. albicans adherence was lower than for fecund controls, but it was higher for cells from 33 postmenopausal diabetic women. The hormonal status of the fecund and postmenopausal women was assayed cytologically by the Karyopyknotic and Maturation Indices, which determine the ratios of superficial, intermediate, and parabasal vaginal epithelial cells. Findings point to increased C. albicans adherence in situations where there is and increase in the number of intermediate epithelial cells: pregnancy, the 1st or 4th weeks of the menstrual cycle, or diabetes. The adherence of 41 C. albicans isolates from patients with vaginitis was significantly higher than that of 36 isolates from asymptomatic carriers.