Sialic acid-based probiotic intervention in lactating mothers improves the neonatal gut microbiota and immune responses by regulating sialylated milk oligosaccharide synthesis via the gut-breast axis.

Human milk oligosaccharides (HMOs) are vital milk carbohydrates that help promote the microbiota-dependent growth and immunity of infants. Sialic acid (SA) is a crucial component of sialylated milk oligosaccharides (S-MOs); however, the effects of SA supplementation in lactating mothers on S-MO biosynthesis and their breastfed infants are unknown. Probiotic intervention during pregnancy or lactation demonstrates promise for modulating the milk glycobiome. Here, we evaluated whether SA and a probiotic (Pro) mixture could increase S-MO synthesis in lactating mothers and promote the microbiota development of their breastfed neonates. The results showed that SA+Pro intervention modulated the gut microbiota and 6'-SL contents in milk of maternal rats more than the SA intervention, which promoted Lactobacillus reuteri colonization in neonates and immune development. Deficient 6'-SL in the maternal rat milk of St6gal1 knockouts (St6gal1-/-) disturbed intestinal microbial structures in their offspring, thereby impeding immune tolerance development. SA+Pro intervention in lactating St6gal1± rats compromised the allergic responses of neonates by promoting 6'-SL synthesis and the neonatal gut microbiota. Our findings from human mammary epithelial cells (MCF-10A) indicated that the GPR41-PI3K-Akt-PPAR pathway helped regulate 6'-SL synthesis in mammary glands after SA+Pro intervention through the gut - breast axis. We further validated our findings using a human-cohort study, confirming that providing SA+Pro to lactating Chinese mothers increased S-MO contents in their breast milk and promoted gut Bifidobacterium spp. and Lactobacillus spp. colonization in infants, which may help enhance immune responses. Collectively, our findings may help alter the routine supplementation practices of lactating mothers to modulate milk HMOs and promote the development of early-life gut microbiota and immunity.

Application of propofol-remifentanil intravenous general anesthesia combined with regional block in pediatric ophthalmic surgery.

OBJECTIVE: The aim of this study is to observe the anesthetic effect and safety of intravenous anesthesia without muscle relaxant with propofol-remifentanil combined with regional block under laryngeal mask airway in pediatric ophthalmologic surgery. METHODS: A total of 90 undergoing ophthalmic surgery were anesthetized with general anesthesia using the laryngeal mask airway without muscle relaxant. They were randomly divided into two groups: 45 children who received propofol-remifentanil intravenous anesthesia combined with regional block (LG group), and 45 children who received total intravenous anesthesia (G group). The peri-operative circulatory indicators, awakening time after general anesthesia, postoperative analgesic effect and the incidence of anesthesia-related adverse events were respectively compared between the two groups. RESULTS: All the children successfully underwent the surgical procedure. The awakening time after general anesthesia and removal time of laryngeal mask were significantly shorter in the LG group than in the G group (P < 0.05). There was no statistically significant difference in the heart rates in the perioperative period between the two groups (P > 0.05). There was no statistically significant difference in the incidence of intraoperative physical response, respiratory depression, postoperative nausea and vomiting (PONV) and emergence agitation (EA) between the two groups (P > 0.05). The pain score at the postoperative hour 2 was lower in the LG group than in the G group (P < 0.05). CONCLUSION: Propofol-remifentanil intravenous anesthesia combined with long-acting local anesthetic regional block anesthesia, combined with laryngeal mask ventilation technology without muscle relaxants, can be safely used in pediatric eye surgery to achieve rapid and smooth recovery from general anesthesia and better postoperative analgesia. This anesthesia scheme can improve the comfort and safety of children in perioperative period, and has a certain clinical popularization value.

Effects of light qualities on growth and physiological-biochemical traits of Scutellaria baicalensis.

Canopy spectral composition significantly affects growth and functional traits of understory plants. In this study, we explored the optimal light condition suitable for enhancing Scutellaria baicalensis's yield and quality, aiming to provide scientific reference for the exploitation and utilization of medicinal plant resources in the understory of forests. We measured the responses of growth, morphology, biomass allocation, physiological traits, and secon-dary metabolites of S. baicalensis to different light qualities. S. baicalensis was cultured under five LED-light treatments including full spectrum light (control), ultraviolet-A (UV-A) radiation, blue, green, and red light. Results showed that UV-A significantly reduced plant height, base diameter, leaf thickness, leaf area ratio, and biomass of each organ. Red light significantly reduced base diameter, biomass, effective quantum yield of photosystem Ⅱ (ФPSⅡ), and total flavonoid concentration. Under blue light, root length and total biomass of S. baicalensis significantly increased by 48.0% and 10.8%, respectively, while leaf number and chlorophyll content significantly decreased by 20.0% and 31.6%, respectively. The other physiological and biochemical traits were consistent with their responses in control. Our results suggested that blue light promoted photosynthesis, biomass accumulation, and secondary metabolite synthesis of S. baicalensis, while red light and UV-A radiation negatively affected physiological and biochemical metabolic processes. Therefore, the ratio of blue light could be appropriately increased to improve the yield and quality of S. baicalensis.

Atropisomeric Carboxylic Acids Synthesis via Nickel-Catalyzed Enantioconvergent Carboxylation of Aza-Biaryl Triflates with CO2.

Upgrading CO2 to value-added chiral molecules via catalytic asymmetric C-C bond formation is a highly important yet challenging task. Although great progress on the formation of centrally chiral carboxylic acids has been achieved, catalytic construction of axially chiral carboxylic acids with CO2 has never been reported to date. Herein, we report the first catalytic asymmetric synthesis of axially chiral carboxylic acids with CO2, which is enabled by nickel-catalyzed dynamic kinetic asymmetric reductive carboxylation of racemic aza-biaryl triflates. A variety of important axially chiral carboxylic acids, which are valuable but difficult to obtain via catalysis, are generated in an enantioconvergent version. This new methodology features good functional group tolerance, easy to scale-up, facile transformation and avoids cumbersome steps, handling organometallic reagents and using stoichiometric chiral materials. Mechanistic investigations indicate a dynamic kinetic asymmetric transformation process induced by chiral nickel catalysis.

[Comparison of Two Methods With a Left-Sided Double-Lumen Tube for Endobronchial Intubation].

Objective To compare the success rates of two methods for endobronchial intubation:the left-sided double-lumen tube(DLT) rotated 90° counter-clockwise with the patient head at the mid positon and the tube rotated 180° counter-clockwise with the patient head turned to the right. Methods Six hundred and forty-eight patients were enrolled in this study,who were to undergo elective thoracic surgery by left-sided DLT intubation in the Peking Union Medical College Hospital from December 2021 to June 2022.They were randomized into a 90° group and a 180° group,with 324 patients in each group.In the 90° group,with the patient head kept at the mid position,the left-sided DLT was advanced until the bronchial cuff passed the vocal cords and then rotated 90° counter-clockwise.In the 180°group,with the left mandible angle of each patient in the straight line with the sternum,the tube was advanced until the bronchial cuff passed the vocal cords and then rotated 180° counter-clockwise.The intubation success rate and the intubation-related complications such as carina mucosal injuries were compared between the two groups. Results The 648 patients included 336 males and 312 females,with the age ranging from 39.0 to 75.0 years old and the average age of(54.6±9.0) years old.The success rate of first intubation was 80.3% in the 90° group and 75.0% in the 180° group,which showed no significant difference(P=0.109).The success rate of second intubation was higher in the 180° group than in the 90° group(P<0.001).The rate of carina mucosal injuries was 23.8% in the 90° group and 25.6% in the 180° group,which showed no significant difference(P=0.585). Conclusions Compared with the conventional method(90°),the intubation of the left-sided DLT rotated 180° counter-clockwise with the patient head turned to the right cannot improve the success rate of the first intubation.However,it could improve the success rate of reintubation as a remedy.

Specific patterns and potential risk factors to predict 3-year risk of death among non-cancer patients with advanced chronic kidney disease by machine learning.

Chronic kidney disease (CKD) is a major public health concern. But there are limited machine learning studies on non-cancer patients with advanced CKD, and the results of machine learning studies on cancer patients with CKD may not apply directly on non-cancer patients. We aimed to conduct a comprehensive investigation of risk factors for a 3-year risk of death among non-cancer advanced CKD patients with an estimated glomerular filtration rate < 60.0 mL/min/1.73m2 by several machine learning algorithms. In this retrospective cohort study, we collected data from in-hospital and emergency care patients from 2 hospitals in Taiwan from 2009 to 2019, including their international classification of disease at admission and laboratory data from the hospital's electronic medical records (EMRs). Several machine learning algorithms were used to analyze the potential impact and degree of influence of each factor on mortality and survival. Data from 2 hospitals in northern Taiwan were collected with 6565 enrolled patients. After data cleaning, 26 risk factors and approximately 3887 advanced CKD patients from Shuang Ho Hospital were used as the training set. The validation set contained 2299 patients from Taipei Medical University Hospital. Predictive variables, such as albumin, PT-INR, and age, were the top 3 significant risk factors with paramount influence on mortality prediction. In the receiver operating characteristic curve, the random forest had the highest values for accuracy above 0.80. MLP, and Adaboost had better performance on sensitivity and F1-score compared to other methods. Additionally, SVM with linear kernel function had the highest specificity of 0.9983, while its sensitivity and F1-score were poor. Logistic regression had the best performance, with an area under the curve of 0.8527. Evaluating Taiwanese advanced CKD patients' EMRs could provide physicians with a good approximation of the patients' 3-year risk of death by machine learning algorithms.

Cu-Catalyzed Asymmetric Dicarboxylation of 1,3-Dienes with CO2.

Dicarboxylic acids and derivatives are important building blocks in organic synthesis, biochemistry, and the polymer industry. Although catalytic dicarboxylation with CO2 represents a straightforward and sustainable route to dicarboxylic acids, it is still highly challenging and limited to generation of achiral or racemic dicarboxylic acids. To date, catalytic asymmetric dicarboxylation with CO2 to give chiral dicarboxylic acids has not been reported. Herein, we report the first asymmetric dicarboxylation of 1,3-dienes with CO2 via Cu catalysis. This strategy provides an efficient and environmentally benign route to chiral dicarboxylic acids with high regio-, chemo-, and enantioselectivities. The copper self-relay catalysis, that is, Cu-catalyzed boracarboxylation of 1,3-dienes to give carboxylated allyl boronic ester intermediates and subsequent carboxylation of C-B bonds to give dicarboxylates, is key to the success of this dicarboxylation. Moreover, this protocol exhibits broad substrate scope, good functional group tolerance, easy product derivatizations, and facile synthesis of chiral liquid crystalline polyester and drug-like scaffolds.

Out-of-set association analysis of lung cancer drugs and symptoms based on clinical case data mining.

BACKGROUND: There are 1.8 million lung cancer deaths worldwide, accounting for 18% of global cancer deaths, including 710,000 in China, accounting for 23.8% of all cancer deaths in China. OBJECTIVE: To explore the out-of-set association rules of lung cancer symptoms and drugs through text mining of traditional Chinese medicine (TCM) treatment of lung cancer, and form medical case analysis to analyze the experience of TCM syndrome differentiation in its treatment. METHODS: The medical records of all patients diagnosed with lung cancer in Nanjing Chest Hospital from January to December 2018 were collected, and the out-of-set association analysis was performed using the MedCase v5.2 TCM clinical scientific research auxiliary platform based on the frequent pattern growth enhanced association analysis algorithm. RESULTS: In terms of TCM treatment of lung cancer, the clinical symptoms with high correlation included cough, expectoration, chest distress, and white phlegm; and the drugs with high correlation included Pinellia ternata, licorice root, white Atractylodes rhizome, and Radix Ophiopogonis; with the prescriptions based on Erchen and Maimendong decoctions. CONCLUSION: This analytical study of the medical cases of TCM treatment for lung cancer was performed using data mining techniques, and the out-of-set association rules between clinical symptoms and drugs were analyzed, including the understanding of lung cancer in TCM. Moreover, the essence of experience in drug use was gathered, providing significant scientific guidance for the clinical treatment of lung cancer.

Endocrine and metabolic comorbidities in primary cicatricial alopecia: A nationwide population-based study.

Primary cicatricial alopecia (PCA) is a rare, scarring, hair loss disorder. Due to its low incidence, little is known about endocrine and metabolic comorbidities in patients with PCA. Thus, we aimed to investigate the association between PCA and endocrine and metabolic disorders. This nationwide, population-based, cross-sectional study included patients diagnosed with PCA or non-cicatricial alopecia (NCA) and normal individuals without history of alopecia registered in the Korean National Health Insurance Service database between January 1, 2011, and December 31, 2020. We calculated the odds ratios of endocrine and metabolic comorbidities of patients with PCA compared to all patients or age- and sex-matched patients with NCA or normal individuals using multivariable logistic regression models. A total of 3 021 483 individuals (mean age [SD], 38.7 [15.0] years, 1 607 380 [53.2%] men), including 11 956 patients with PCA, 601 852 patients with NCA, and 2 407 675 normal participants, were identified. Patients with PCA had an increased risk for dyslipidemia (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 1.06-1.24), diabetes (aOR 1.38, 95% CI 1.24-1.53), and hypertension (aOR 1.10, 95% CI 1.02-1.19) compared to matched patients with NCA. Regarding PCA subtypes, lichen planopilaris/frontal fibrosing alopecia was positively associated with hypothyroidism (aOR 2.03, 95% CI 1.44-2.86) compared to NCA. Folliculitis decalvans and dissecting cellulitis were positively associated with dyslipidemia (aOR 1.16, 95% CI 1.05-1.28 and aOR 1.16, 95% CI 1.04-1.29, respectively), diabetes (aOR 1.38, 95% CI 1.20-1.58 and aOR 1.52, 95% CI 1.32-1.74, respectively), and hypertension (aOR 1.10, 95% CI 1.00-1.20 and aOR 1.14, 95% CI 1.02-1.27, respectively). Similar trends were observed when each PCA subgroup was compared with the normal control group. This study demonstrates that patients with PCA are more likely to have endocrine and metabolic comorbidities than patients without PCA. Further research on these comorbidities may improve the understanding of PCA.

Progress and challenges of plant-derived nucleic acids as therapeutics in macrophage-mediated RNA therapy.

Plant-derived nucleic acids, especially small RNAs have been proved by increasing evidence in the pharmacological activities and disease treatment values in macrophage meditated anti-tumor performance, immune regulating functions and antiviral activities. But the uptake, application and delivery strategies of RNAs as biodrugs are different from the small molecules and recombinant protein drugs. This article summarizes the reported evidence for cross-kingdom regulation by plant derived functional mRNAs and miRNAs. Based on that, their involvement and potentials in macrophage-mediated anti-tumor/inflammatory therapies are mainly discussed, as well as the load prospect of plant RNAs in viruses and natural exosome vehicles, and their delivery to mammalian cells through macrophage were also summarized. This review is to provide evidence and views for the plant derived RNAs as next generation of drugs with application potential in nucleic acid-based bio-therapy.

An Information Fusion System-Driven Deep Neural Networks With Application to Cancer Mortality Risk Estimate.

Next-generation sequencing (NGS) genomic data offer valuable high-throughput genomic information for computational applications in medicine. Using genomic data to identify disease-associated genes to estimate cancer mortality risk remains challenging regarding to computational efficiency and risk integration. For determining mortality-related genes, we propose an information fusion system based on a fuzzy system to fuse the numerous deep-learning-based risk scores, consider the significance of features related to time-varying effects and risk stratifications, and interpret the directional relationship and interaction between outcome and predictors. Fuzzy rules were implemented to integrate the considerations mentioned above by merging all the risk score models to achieve advanced risk estimation. The genomic data of head and neck squamous cell carcinoma (HNSCC) were used to evaluate the performance of the proposed computational approach. The results indicated that the proposed computational approach exhibited optimal ability to identify mortality risk-related genes in HNSCC patients. The results also suggest that HNSCC mortality is associated with cancer inflammatory response, the interleukin-17A signaling pathway, stellate cell activation, and the extracellular-regulated protein kinase five signaling pathway, which might offer new therapeutic targets HNSCC through immunologic or antiangiogenic mechanisms. The proposed information fusion system can promote the determination of high-risk genes related to cancer mortality. This study contributes a valid cancer mortality risk estimate that can identify mortality-related genes.

In vitro protective effect of recombinant prominin-1 combined with microRNA-29b on N-methyl-D-aspartate-induced excitotoxicity in retinal ganglion cells.

AIM: To determine the in vitro protective effect of recombinant prominin-1 (Prominin-1)+microRNA-29b (P1M29) on N-methyl-D-aspartate (NMDA)-induced excitotoxicity in retinal ganglion cells (RGCs). METHODS: RGC-5 cells were cultured, and NMDA-induced excitotoxicity at the range of 100-800 µmol/L was assessed using the MTT assay. NMDA (800 µmol/L) was selected as the appropriate concentration for preparing the cell model. To evaluate the protective effect of P1M29 on the cell model, Prominin-1 was added at the concentration of 1-6 ng/mL for 48h, and the cell survival was investigated with/without microRNA-29b. After obtaining the appropriate concentration and time of P1M29 at 48h, real-time polymerase chain reaction (PCR) was utilized to detect the relative mRNA expression of vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-ß2. Western blot detection was applied to measure the phosphorylation levels of protein kinase B (AKT) and extracellular regulated protein kinases (ERK) in RGC-5 cells after treatment with Prominin-1. Apoptosis study of the cell model was conducted by flow cytometry for estimating the anti-apoptotic effect of P1M29. Immunofluorescence analysis was used to analyze the expression levels of VEGF and TGF-ß2. RESULTS: MTT cytotoxicity assays demonstrated that P1M29 group had significantly higher cell survival rate than Prominin-1 group (P<0.05). Real-time PCR data indicated that the expression levels of VEGF were significantly increased in both Prominin-1 and P1M29 groups compared NMDA and microRNA-29b group (P<0.05), while TGF-ß2 were significantly decreased in both microRNA-29b and P1M29 groups compared NMDA and Prominin-1 group (P<0.05). Western blot results showed that both Prominin-1 and P1M29 groups significantly increased the phosphorylation levels of AKT and ERK compared to NMDA and microRNA-29b groups (P<0.05). Flow cytometry analysis revealed that P1M29 could prevent RGC-5 cell apoptosis in the early stage of apoptosis, while immunofluorescence results showed that P1M29 group had higher expression of VEGF and lower expression of TGF-ß2 with a stronger green fluorescence than NMDA group. CONCLUSION: Prominin-1 combined with microRNA-29b can provide a suitable therapeutic option for ameliorating NMDA-induced excitotoxicity in RGC-5 cells.

m6A modification associated with YTHDF1 is involved in Japanese encephalitis virus infection.

N6-methyladenosine (m6A), the most common modification in mammalian mRNA and viral RNA, regulates mRNA structure, stability, translation, and nuclear export. The Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus causing severe neurologic disease in humans. To date, the role of m6A modification in JEV infection remains unclear. Herein, we aimed to determine the impact of m6A methylation modification on JEV replication in vitro and in vivo. Our results demonstrated that the overexpression of the m6A reader protein YTHDF1 in vitro significantly inhibits JEV proliferation. Additionally, YTHDF1 negatively regulates JEV proliferation in YTHDF1 knockdown cells and YTHDF1 knockout mice. MeRIP-seq analysis indicated that YTHDF1 interacts with several interferon-stimulated genes (ISGs), especially in IFIT3. Overall, our data showed that YTHDF1 played a vital role in inhibiting JEV replication. These findings bring novel insights into the specific mechanisms involved in the innate immune response to infection with JEV. They can be used in the development of novel therapeutics for controlling JEV infection.

The promoting effects of Grin2d expression in tumorigenesis and the aggressiveness of esophageal cancer.

Grin2d is an ionotropic NMDA receptor, a subunit of glutamate-dependent, and a facilitator of cellular calcium influx in neuronal tissue. In this study, we found that Grin2d expression was higher in esophageal cancer than in normal mucosa at both the mRNA and protein level using RT-PCR, bioinformatics analysis, and western blotting (p<0.05). Grin2d mRNA expression was positively correlated with old age, white race, heavy weight, distal location, adenocarcinoma, cancer with Barrett's lesion, or high-grade columnar dysplasia (p<0.05). The differential genes associated with Grin2d mRNA were involved in fat digestion and absorption, cholesterol metabolism, lipid transfer, lipoproteins, synaptic membranes, and ABC transporters (p<0.05). The Grin2d-related genes were classified into the following categories: metabolism of glycerolipids, galactose, and O-glycan, cell adhesion binding, actin binding, cadherin binding, the Hippo signaling pathway, cell-cell junctions, desmosomes, DNA-transcription activator binding, and skin development and differentiation (p<0.05). Grin2d immunoreactivity was positively correlated with distal metastasis and unfavorable overall survival in esophageal cancer (p<0.05). Grin2d overexpression promoted proliferation, migration, and invasion in esophageal cancer cells but blocked apoptosis (p<0.05) and increased the expression of PI3K, Akt and p-mTOR. Grin2d knockout caused the opposite effects. These findings indicated that upregulated Grin2d expression played an important role in esophageal carcinogenesis via the PI3K/Akt/mTOR pathway and might be a biological marker for aggressive tumor behavior and poor prognosis. Its silencing might represent a targeted therapy approach against esophageal cancer.

Assessment of Effects of Low-Level Light Therapy on Scalp Condition and Hair Growth.

Background: The appearance of the scalp and hair is very important aesthetically regardless of age or sex. Although there are many drugs and treatment methods for scalp problems and hair loss, the treatment response is still insufficient. Aims and Objectives: To evaluate the efficacy of low-level light therapy in a helmet-like device. Materials and Methods: This study was designed as a 24-week trial with 50 participants. All participants used a helmet-shaped device emitting 630-690, 820-880, and 910-970 nm light wavelengths, for 20 minutes, daily for 24 weeks. A phototrichogram for hair density and thickness, Global Aesthetic Improvement Scale score, erythema index, and sebum secretions of the scalp were evaluated at baseline and at 12 and 24 weeks. Results: After 24 weeks of treatment, hair density and hair thickness were found to have significantly increased (P <.01 and P =0.013, respectively) and sebum secretion of vertex area had decreased significantly (P <.01). Of 49 participants, 73.47% of the participants showed improvement in the overall appearance of the scalp (n = 36). Conclusion: A helmet-like low-level light therapy device can improve the appearance of the hair, with thickening and increase in the density of the hair, and can improve scalp condition by decreasing sebum secretion.

Robotic thyroidectomy using gas-insufflation one-step single-port transaxillary (GOSTA) approach.

BACKGROUND: We conducted this study to report our novel robotic thyroidectomy using gas-insufflation one-step single-port transaxillary (GOSTA) approach and compare it with a conventional transaxillary (CTA) approach using a retraction method for intraoperative and postoperative outcomes. METHODS: We retrospectively analyzed 354 patients who underwent robotic thyroidectomy between January 2019 and April 2023. Of these patients, 143 underwent the procedure through the GOSTA approach, which involves a small incision of 3 cm along the axillary folds with both arms down and a gas-insufflation, from skin flap creation to the completion of thyroidectomy as a one-step single-port procedure without the need for a retractor. The remaining 211 patients underwent the CTA approach. We analyzed the GOSTA approach and compared the surgical outcomes of the GOSTA (n = 100) and CTA (n = 167) approaches in patients with differentiated thyroid cancer who underwent thyroid lobectomy. RESULTS: Out of the 143 patients who underwent the GOSTA approach, 12 underwent total thyroidectomy and 9 underwent lateral neck lymph node dissection with total thyroidectomy. GOSTA-thyroid lobectomy was performed on 122 patients; of these, 100 were diagnosed with differentiated thyroid carcinoma. A comparative study with the CTA approach was only conducted in patients who underwent thyroid lobectomy. No significant differences were found in operative time, hospital stay, or complications between the two groups. CONCLUSIONS: Despite proceeding in one-step with a single smaller incision, from skin flap creation to the completion of thyroidectomy, the GOSTA approach is as feasible and safe as the CTA approach. Additionally, the GOSTA approach allows for thyroidectomy without using a retractor and reduces the workload for the surgeon and assistants.

Alterations of milk oligosaccharides in mothers with gestational diabetes mellitus impede colonization of beneficial bacteria and development of RORγt+ Treg cell-mediated immune tolerance in neonates.

Gestational diabetes mellitus (GDM) is an increasing public health concern that significantly increases the risk of early childhood allergic diseases. Altered maternal milk glycobiome may strongly affect gut microbiota and enteric-specific Treg cell-mediated development of immune tolerance in GDM infants. In this study, we found that, compared with healthy Chinese mothers, mothers with GDM had significantly lower levels of total and specific human milk oligosaccharides (HMOs) in their colostrum that subsequently increased with extension of lactation. This alteration in HMO profiles significantly delayed colonization of Lactobacillus and Bifidobacterium spp. in their breast-fed infants, resulting in a distinct gut microbial structure and metabolome. Further experiments in GDM mouse models indicated that decreased contents of milk oligosaccharides, mainly 3'-sialyllactose (3'-SL), in GDM maternal mice reduced colonization of bacteria, such as L. reuteri and L. johnsonii, in the neonatal gut, which impeded development of RORγt+ regulatory T (Treg) cell-mediated immune tolerance. Treatment of GDM neonates with 3'-SL, Lactobacillus reuteri (L. reuteri) and L. johnsonii promoted the proliferation of enteric Treg cells and expression of transcription factor RORγt, which may have contributed to compromising ovalbumin (OVA)-induced allergic responses. In vitro experiments showed that 3'-SL, metabolites of L. johnsonii, and lysates of L. reuteri stimulated differentiation of mouse RORγt+ Treg cells through multiple regulatory effects on Toll-like receptor, MAPK, p53, and NOD-like receptor signaling pathways. This study provides new ideas for the development of gut microbiota and immune tolerance in GDM newborns.