As the prevalence of allergy and autoimmune disease in industrialized societies continues to rise, improving our understanding of the mechanistic roles behind microbiota-immune homeostasis has become critical for informing therapeutic interventions in cases of dysbiosis. Of particular importance, are alterations to intestinal microbiota occurring within the critical neonatal window, during which the immune system is highly vulnerable to environmental exposures. This review will highlight recent literature concerning mechanisms of early-life microbiota-immune homeostasis as well as discuss the potential for therapeutics in restoring dysbiosis in early life.

Early-life microbiota-immune homeostasis

Objective Gestational diabetes mellitus (GDM) is a condition of glucose intolerance, which may be accompanied with inflammation. The levels of hematological parameters during pregnancy can reflect inflammatory conditions in pregnant women. This study aims to describe the dynamic change of blood cell parameters from the first trimester (6–12 weeks of gestation) to the second trimester (24–28 weeks of gestation) and to investigate the associations of these biomarkers with the risk of GDM. Methods This study was a prospective double-center study conducted in Beijing, China (clinical trial number: NCT03246295). Hematological parameters were tested four times during the follow-up. Logistic regression analysis and Receiver Operating Characteristic (ROC) curve analysis were used to explore the association and predictive ability of hematological parameters for GDM. Results There were 258 of 1027 pregnant women in our study developed GDM. Among the 1027 pregnant women, white blood cells (WBC) gradually increased, and red blood cells (RBC), hemoglobin (HGB), and platelet (PLT) tended to decrease from the first trimester to second trimester. After adjusting for confounding factors, higher levels of RBC, HGB, and PLT in both early and middle pregnancy were positively associated with GDM risk, whereas the level of WBC was associated with GDM risk only in early pregnancy. WBC, RBC, HGB, and PLT in early and middle pregnancy were all correlated with fasting insulin (FINS) in early pregnancy. Conclusion Higher levels of hematological parameters in early and middle pregnancy were associated with glucose metabolism in early pregnancy and the subsequent risk of GDM.

The Association of Hematological Parameters in Early and Middle Pregnancy with the Risk of Gestational Diabetes Mellitus

The aim of the study was to investigate the association between maternal dietary iron intake during pregnancy and the gut microbiota characteristics of both the mother and neonate in a well-characterized cohort. A total of 95 mother-neonate dyads were included in our study, with basic information collected through questionnaires. A semi-quantitative Food Frequency Questionnaire (FFQ) was used to assess maternal dietary intake during pregnancy, and maternal dietary iron intake was categorized into &amp;amp;lt;20 mg/d and ≥20 mg/d groups. Fecal samples were collected from the mother in the third trimester and the neonate, allowing for assessment of the community profile and diversity of gut microbiota via 16S rRNA amplicon sequencing. Then, a comparison between different maternal dietary iron intake groups was conducted, adjusting for delivery mode (VD, vaginal delivery; CS, cesarean section) and other potential confounding factors. No significant differences in community profile and diversity were observed for the maternal gut microbiota in different dietary iron intake groups. In neonate fecal samples, the Shannon (P = 0.044) and Simpson (P = 0.010) diversity indices of the gut microbiota were higher in the maternal dietary iron intake ≥20 mg/d group, while Simpson diversity presented the same tendency in vaginal delivery (P = 0.041) after stratification. The relative abundance of the core genus Bifidobacterium showed a significant difference between groups (4.69 [1.19–12.77] vs. 13.98 [3.44–27.28]; P = 0.044). The abundance of Lactobacillus was different in the ≥20 mg/d group under both delivery modes (VD: beta = 2.9, w = 4.13; CS: beta = 2.77, w = 3.8). Our findings suggest that adequate dietary iron intake during pregnancy may promote beneficial bacterial colonization and increase the biodiversity of the neonate gut microbiota. 

Maternal Dietary Iron Intake during Pregnancy Has a Potential Effect on the Neonate Gut Microbiota Profile

We aimed to examine the effects of antibiotic and probiotic usage on the gut microbiota structure and the presence of antibiotic-resistance genes (ARGs) in infants during the first six months of life. Questionnaires and fecal samples were collected within three days of birth, two months, and six months to assess antibiotic and probiotic exposure. Gut microbiotas were sequenced via 16S rRNA, and ARGs were conducted by qPCR, including beta-lactam (mecA, blaTEM), tetracycline (tetM), fluoroquinolone (qnrS), aminoglycoside (aac(6′)-Ib), and macrolide (ermB). Infants were categorized by antibiotic and probiotic usage and stratified by delivery mode, microbial composition, and ARG abundances were compared, and potential correlations were explored. A total of 189 fecal samples were analyzed in this study. The gut microbiota diversity (Chao1 index) was significantly lower in the “only probiotics” (PRO) group compared to the “neither antibiotics nor probiotics” (CON) group at six months for the CS stratification (p = 0.029). Compositionally, the abundance of core genus Bifidobacterium_pseudocatenulatum was less abundant for the antibiotic during delivery (IAP) group than that in the CON group within the first three days (p = 0.009), while core genus Enterococcus_faecium was more abundant in the PRO than that in the CON group (p = 0.021) at two months. ARGs were highly detected, with Enterococcus hosting tetM and Escherichia associated with blaTEM within three days of birth, though no correlation was found between Bifidobacterium and ARGs. These findings emphasized the critical importance of carefully managing antibiotic and probiotic exposures in early life, with implications for promoting lifelong health through preserving a healthy infant gut ecosystem. 

Unraveling the Microbial Symphony: Impact of Antibiotics and Probiotics on Infant Gut Ecology and Antibiotic Resistance in the First Six Months of Life

Objective: Gestational diabetes mellitus (GDM) is a condition in which glucose intolerance is first recognized during pregnancy. It affects a substantial percentage of pregnancies globally, with a significant prevalence in India. Iron supplementation is often recommended to prevent anemia, but caution is advised in GDM due to the potential inflammatory effects. Elevated hemoglobin (Hb) levels, associated with excess iron, may increase the risk of GDM. This study aims to investigate the differences in Hb and various other blood parameters between controlled and uncontrolled GDM mothers attending antenatal OPD for a regular check-up.
Methods: This cross-sectional study was conducted among 100 women diagnosed with GDM at a tertiary care hospital in Western Tamil Nadu after obtaining ethical clearance and informed consent from the participants. Routine blood investigations, like a complete hemogram, HbA1C, renal and liver function tests, and lipid profiles, were recorded. Participants were categorized based on HbA1C values (<6.5 as normal, >6.5 as abnormal). Differences in blood parameters between the two groups were statistically analyzed.
Results: The study found no significant differences in age, weight, height, or BMI between the controlled and uncontrolled GDM groups. Mean HbA1c levels were 5.58±0.41 and 6.98±1.23 in controlled and uncontrolled GDM groups, respectively. Comparing hematological parameters, the controlled GDM group exhibited higher mean red blood cell (RBC) levels (4.6±0.69 vs. 4.12±0.92) but lower Hb levels (12.25±2.26 vs. 11.01±3.59) than the uncontrolled GDM group. There were no significant differences in platelet, lymphocyte, and MCH levels. Urea, triglycerides, and globulin levels were higher in the uncontrolled GDM group, but all values remained within normal limits.
Conclusion: Elevated Hb levels were associated with uncontrolled GDM, indicating a potential risk factor. The study underscores the importance of monitoring iron levels in GDM patients. In addition, heightened white blood cell counts and altered hematological parameters suggest an inflammatory component in uncontrolled GDM. Further research is warranted to explore these associations and their clinical implications for managing GDM effectively.

Impact of gestational diabetes mellitus on hematological parameters, liver function, renal function, and lipid profile in antenatal women at a tertiary care hospital

What is already known about this topic? Hematological parameters may indicate the presence of chronic low-grade inflammation and increasing viscosity, which are involved in the pathological processes of gestational diabetes mellitus (GDM). However, the association between several hematological parameters in early pregnancy and GDM has yet to be elucidated. What is added by this report? Hematological parameters in the first trimester, particularly red blood cell (RBC) count and systematic immune index, have a significant impact on GDM incidence. The neutrophils (NEU) count in the first trimester was particularly pronounced for GDM. The upward trend of RBC, white blood cell (WBC), and NEU counts was consistent across all GDM subtypes. What are the implications for public health practice? Early pregnancy hematological parameters are associated with the risk of GDM.

/pdf/hematological-parameters-in-the-first-trimester-and-the-risk-4qahzk7n.pdf

Hematological Parameters in the First Trimester and the Risk of Gestational Diabetes Mellitus — Beijing, China, 2017–2020

Unreasonable use of antibiotics and probiotics can alter the gut ecology, leading to antibiotic resistance and suboptimal health outcomes during early life. Our study aims are to clarify the association among antibiotic and probiotic exposure in early life, the microecology of the gut microbiota, and the development of antibiotic resistance; to investigate the long-term impact of antibiotics and probiotics on the health outcomes of infants and young children; and to provide a theoretical basis for the rational use of antibiotics and probiotics from a life course perspective.The study is a prospective, longitudinal birth cohort study conducted in Shaanxi Province, China from 2018 to 2024. A total of 3,000 eligible mother-child pairs will be enrolled from rural, suburban, and urban areas. The recruitment of the participants begins at pregnancy, and the newborns will be followed up for 2 years at successive timepoints: within 3 days after birth, 42 days after birth, and at 3, 6, 12, 18, and 24 months of age. Sociodemographic data, environmental exposures, dietary patterns, psychological conditions, and medical and drug histories are collected. Cognitive and behavioural development among infants and young children and questionnaires on antibiotic knowledge and behaviour among caregivers will be collected at 12 and 24 months of age. The faecal samples are collected and analysed by 16S rRNA high-throughput sequencing and quantitative PCR (qPCR) for antibiotic resistance genes.The findings will inform antibiotic and probiotic use for pregnant women and infants and contribute to establishing rational use strategies of antibiotics and probiotics for paediatricians, health practitioners, and drug administration policy-makers.The study was registered on the Chinese Clinical Trial Registry (ChiCTR) platform, http://www.chictr.org.cn (Record ID: ChiCTR2100047531, June 20, 2021). 

/pdf/the-impact-of-early-life-antibiotics-and-probiotics-on-gut-2ifkonmn.pdf

The impact of early-life antibiotics and probiotics on gut microbial ecology and infant health outcomes: a Pregnancy and Birth Cohort in Northwest China (PBCC) study protocol

Association of Optimal Gestational Weight Gain with Pregnancy Outcomes in Twin Pregnancies in China：A Multicenter Retrospective Study

<h2>Abstract</h2><h3>Objective</h3> To examine the association of serum connecting peptide (C-peptide) concentrations with gestational diabetes mellitus (GDM) risk among Chinese women. <h3>Methods</h3> A nested case-control study was conducted on 436 reproductive-aged women, involving 218 GDM cases and 218 controls matched at 1:1 by maternal age, in Beijing, China between January 2016 and December 2017. Fasting serum C-peptide were successively determined at 10–14 and 15–20 weeks of gestation. Restricted cubic spline and logistic regression analyses were utilized, and receiver operating characteristic (ROC) curves were generated to evaluate the predictive capacity of C-peptide for GDM. <h3>Results</h3> Fasting serum C-peptide concentrations exhibited a significant decrease from the initial to the subsequent trimester in females with normal glucose tolerance (NGT). For each 1 log ng/mL increase of fasting serum C-peptide during the first and second trimesters, GDM risk increased by 2.38-fold [odds ratio (OR): 2.38, 95% confidence intervals (95%CI): 1.33–4.40] and 3.07-fold (OR: 3.07, 95%CI: 1.49–6.62), respectively. The areas under the ROC curves for the first- and second-trimester C-peptide were 80.4% and 82.4%. <h3>Conclusion</h3> Our findings revealed a positive correlation between fasting serum C-peptide during the first and second trimesters and the risk of GDM or its subtypes, underscoring the potential of C-peptide as a predictor for GDM development. 

Maternal fasting serum C-peptide concentrations in the first and second trimesters and subsequent risk of gestational diabetes mellitus: A nested case-control study among Chinese women.

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Hematological Parameters in the First Trimester and the Risk of Gestational Diabetes Mellitus — Beijing, China, 2017–2020

The impact of early-life antibiotics and probiotics on gut microbial ecology and infant health outcomes: a Pregnancy and Birth Cohort in Northwest China (PBCC) study protocol

Association of Optimal Gestational Weight Gain with Pregnancy Outcomes in Twin Pregnancies in China：A Multicenter Retrospective Study

Maternal fasting serum C-peptide concentrations in the first and second trimesters and subsequent risk of gestational diabetes mellitus: A nested case-control study among Chinese women.