scholarly journals First trimester gut microbiome induces Inflammation-dependent gestational diabetes phenotype in mice

Author(s):  
Yishay Pinto ◽  
Sigal Frishman ◽  
Sondra Turjeman ◽  
Adi Eshel ◽  
Meital Nuriel-Ohayon ◽  
...  

AbstractGestational diabetes mellitus (GDM) is a condition in which non-diabetic women are diagnosed with glucose intolerance during pregnancy, typically in the second trimester. GDM can lead to a wide range of obstetrical and metabolic complications for both mother and neonate1. Early identification of GDM risk, along with a better understanding of its pathophysiology during the first trimester of pregnancy, may be effective in reducing GDM incidence, as well as its associated short and long term morbidities2. Here, we comprehensively profiled the gut microbiome, metabolome, inflammatory cytokines, nutrition and clinical records of 394 women during the first trimester of pregnancy. We found elevated levels of proinflammatory serum cytokines in those who later developed GDM. The women’s stool samples were also characterized by decreased levels of several fecal short-chain fatty acids and altered microbiome. We next tested the hypothesis that differences in GDM-associated microbial composition during the first trimester drove inflammation and insulin-resistance. Stool samples collected early in pregnancy from women from three populations who did and did not later develop GDM were transplanted to germ-free mice and confirmed that both inflammation and insulin-resistance are induced by the microbiome of pregnant women more than 10 weeks prior to GDM diagnosis. Following these observations, we used a machine-learning approach to predict GDM based on first trimester clinical, microbial and inflammatory markers. Our model showed high predictive accuracy. Overall, our results suggest that the gut microbiome of women in the first trimester plays a remarkable role in inflammation-induced GDM pathogenesis and point to dozens of GDM markers during the first trimester of pregnancy, some of which may be targets for therapeutic intervention.

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Chuyao Jin ◽  
Lizi Lin ◽  
Na Han ◽  
Zhiling Zhao ◽  
Zheng Liu ◽  
...  

Abstract Background To assess the association between plasma retinol-binding protein 4 (RBP4) levels both in the first trimester and second trimester and risk of gestational diabetes mellitus (GDM). Methods Plasma RBP4 levels and insulin were measured among 135 GDM cases and 135 controls nested within the Peking University Birth Cohort in Tongzhou. Multivariable linear regression analysis was conducted to assess the influence of RBP4 levels on insulin resistance. Conditional logistic regression models were used to compute the odds ratio (OR) and 95% confidence interval (CI) between RBP4 levels and risk of GDM. Results The GDM cases had significantly higher levels of RBP4 in the first trimester than controls (medians: 18.0 μg/L vs 14.4 μg/L; P < 0.05). Plasma RBP4 concentrations in the first and second trimester were associated with fasting insulin, homeostasis model assessment for insulin resistance (HOMA-IR), and the quantitative insulin sensitivity check index (QUICKI) in the second trimester (all P < 0.001). With adjustment for diet, physical activity, and other risk factors for GDM, the risk of GDM increased with every 1-log μg/L increment of RBP4 levels, and the OR (95% CI) was 3.12 (1.08–9.04) for RBP4 in the first trimester and 3.38 (1.03–11.08) for RBP4 in the second trimester. Conclusions Plasma RBP4 levels both in the first trimester and second trimester were dose-dependently associated with increased risk of GDM.


Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 246
Author(s):  
Felix C.F. Schmitt ◽  
Martin Schneider ◽  
William Mathejczyk ◽  
Markus A. Weigand ◽  
Jane C. Figueiredo ◽  
...  

Changes in the gut microbiome have already been associated with postoperative complications in major abdominal surgery. However, it is still unclear whether these changes are transient or a long-lasting effect. Therefore, the aim of this prospective clinical pilot study was to examine long-term changes in the gut microbiota and to correlate these changes with the clinical course of the patient. Methods: In total, stool samples of 62 newly diagnosed colorectal cancer patients undergoing primary tumor resection were analyzed by 16S-rDNA next-generation sequencing. Stool samples were collected preoperatively in order to determine the gut microbiome at baseline as well as at 6, 12, and 24 months thereafter to observe longitudinal changes. Postoperatively, the study patients were separated into two groups—patients who suffered from postoperative complications (n = 30) and those without complication (n = 32). Patients with postoperative complications showed a significantly stronger reduction in the alpha diversity starting 6 months after operation, which does not resolve, even after 24 months. The structure of the microbiome was also significantly altered from baseline at six-month follow-up in patients with complications (p = 0.006). This was associated with a long-lasting decrease of a large number of species in the gut microbiota indicating an impact in the commensal microbiota and a long-lasting increase of Fusobacterium ulcerans. The microbial composition of the gut microbiome shows significant changes in patients with postoperative complications up to 24 months after surgery.


Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1568 ◽  
Author(s):  
David Simmons ◽  
Roland Devlieger ◽  
Andre van Assche ◽  
Sander Galjaard ◽  
Rosa Corcoy ◽  
...  

Excess gestational weight gain (GWG) is associated with the development of gestational diabetes mellitus (GDM). Lifestyle trials have not achieved much GWG limitation, and have largely failed to prevent GDM. We compared the effect of substantial GWG limitation on maternal GDM risk. Pregnant women with a body mass index (BMI) ≥29 kg/m2 <20 weeks gestation without GDM (n = 436) were randomized, in a multicenter trial, to usual care (UC), healthy eating (HE), physical activity (PA), or HE and PA lifestyle interventions. GWG over the median was associated with higher homeostasis model assessment insulin resistance (HOMA-IR) and insulin secretion (Stumvoll phases 1 and 2), a higher fasting plasma glucose (FPG) at 24–28 weeks (4.66 ± 0.43 vs. 4.61 ± 0.40 mmol/L, p < 0.01), and a higher rate of caesarean section (38% vs. 27% p < 0.05). The GWG over the median at 35–37 weeks was associated with a higher rate of macrosomia (25% vs. 16%, p < 0.05). A post hoc comparison among women from the five sites with a GWG difference >3 kg showed no significance difference in glycaemia or insulin resistance between HE and PA, and UC. We conclude that preventing even substantial increases in GWG after the first trimester has little effect on maternal glycaemia. We recommend randomized controlled trials of effective lifestyle interventions, starting in or before the first trimester.


Author(s):  
Zehra Vural Yılmaz ◽  
Elif Yılmaz ◽  
Bilal İçer ◽  
Tuncay Küçüközkan

<p><strong>Objective:</strong> The aim of this study is to evaluate the relationship between hematological changes in early pregnancy using complete blood count parameters and gestational diabetes mellitus.<br /><strong>Study Design:</strong> One hundred pregnant with gestational diabetes mellitus and one hundred healthy pregnant were included in the study. Blood samples for routine complete blood count parameters in first trimester of pregnancy were analyzed. <br /><strong>Results:</strong> In the gestational diabetes mellitus group white blood cell, platelet count, neutrophil and lymphocyte count, mean platelet volume, red cell distribution width were significantly higher than control group. However, there was no significant difference between groups with regard to neutrophil to lymphocyte ratio and platelet to lymphocyte ratio levels. In binary logistic regression analysis; first trimester mean platelet volume and red cell distribution width values were found to be independently associated with diagnosis of gestational diabetes mellitus. <br /><strong>Conclusion:</strong> This study demonstrates that hematological parameters in first trimester of pregnancy are closely associated with gestational diabetes mellitus. The parameters that are routinely and automatically calculated in complete blood count; may be used to predict gestational diabetes mellitus.</p>


2019 ◽  
Vol 13 (11) ◽  
pp. 1439-1449 ◽  
Author(s):  
Marjolein A Y Klaassen ◽  
Floris Imhann ◽  
Valerie Collij ◽  
Jingyuan Fu ◽  
Cisca Wijmenga ◽  
...  

Abstract Background and Aims Crohn’s disease [CD] is a chronic inflammatory disorder of the gastrointestinal tract characterised by alternating periods of exacerbation and remission. We hypothesised that changes in the gut microbiome are associated with CD exacerbations, and therefore aimed to correlate multiple gut microbiome features to CD disease activity. Methods Faecal microbiome data generated using whole-genome metagenomic shotgun sequencing of 196 CD patients were of obtained from the 1000IBD cohort [one sample per patient]. Patient disease activity status at time of sampling was determined by re-assessing clinical records 3 years after faecal sample production. Faecal samples were designated as taken ‘in an exacerbation’ or ‘in remission’. Samples taken ‘in remission’ were further categorised as ‘before the next exacerbation’ or ‘after the last exacerbation’, based on the exacerbation closest in time to the faecal production date. CD activity was correlated with gut microbial composition and predicted functional pathways via logistic regressions using MaAsLin software. Results In total, 105 bacterial pathways were decreased during CD exacerbation (false-discovery rate [FDR] &lt;0.1) in comparison with the gut microbiome of patients both before and after an exacerbation. Most of these decreased pathways exert anti-inflammatory properties facilitating the biosynthesis and fermentation of various amino acids [tryptophan, methionine, and arginine], vitamins [riboflavin and thiamine], and short-chain fatty acids [SCFAs]. Conclusions CD exacerbations are associated with a decrease in microbial genes involved in the biosynthesis of the anti-inflammatory mediators riboflavin, thiamine, and folate, and SCFAs, suggesting that increasing the intestinal abundances of these mediators might provide new treatment opportunities. These results were generated using bioinformatic analyses of cross-sectional data and need to be replicated using time-series and wet lab experiments.


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