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Bacteria, as the major component of the human microbiome, have been shown to play important physiological roles in human health and disease development. However, a growing body of research suggests that fungi, which make up less than 1% of the human microbiome, also have a significant impact on human health, particularly in early life. Fungal colonization is strongly associated with the onset of future childhood diseases such as infectious diseases, allergic diseases, and intestinal diseases. Factors influencing early life, such as mode of birth and use of antibiotics, may be involved in the development of related diseases by affecting fungal colonization, but more research is needed to summarize this. This article reviews the characteristics of the fungal composition in the first 1 000 days of life, the related factors influencing the colonization of the early life fungal community, and the association between fungal dysbiosis and childhood diseases, providing a reference for the prevention and control of related childhood diseases.

Maintaining immune homeostasis is crucial for neonatal health following birth, as neonates encounter the colonization of gut flora and a plethora of external antigens. Myeloid-derived suppressor cells (MDSCs), a group of innate immune cells of myeloid origin with immunosuppressive functions, are known for their significant role in promoting tumor progression. Recent studies, however, have highlighted the critical immunoprotective functions of neonatal MDSCs. Unlike tumor-associated MDSCs, neonatal MDSCs exhibit strong antibacterial activity and play a vital role in preventing inflammatory responses in newborns. This review provides a comprehensive overview of the etiology, characteristics, immunomodulatory functions, and regulatory mechanisms of neonatal MDSCs, emphasizing their role in neonatal inflammatory diseases. This insight aims to provide new strategies for the immunotherapy of neonatal inflammatory diseases.

Early life is a critical window period that determines the growth and development of children, but this delicate and complex period is highly susceptible to the disturbance of various exogenous chemicals, which in consequence may lead to short-term or long-term adverse health effects in human beings. The massive use of antibiotics has contributed to widespread exposure in early life, along with the potentially adverse effects on child health, and has caused great concern in public health. This review summarized recent epidemiological studies on the population with early-life antibiotic exposure and associated health outcomes such as growth and development, allergies, and psycho-behavioral problems in children, as well as potential biological mechanisms underlying these associations. Current findings suggested that antibiotic exposure early in life, including pregnancy and infancy, is strongly associated with childhood allergic diseases (e.g., atopic dermatitis and asthma), growth and development (e.g., obesity and birth length), and childhood psycho-behavioral problems (e.g., autism and anxiety). It also suggested that antibiotic exposure may affect individual health through gut microbiota, thyroid function, inflammation factors, mitochondrial function, and epigenetic mechanisms. In the future, more large prospective birth cohorts should be established to determine the levels of internal exposure to different types of antibiotics at multiple time points in early life and to explore their associations with child health outcomes, as well as to further validate relevant mechanisms, aiming to provide high-quality scientific evidence for research on child health associated with environmental exposure in early life.

Cadmium exposure during pregnancy is a non-negligible public health problem which may increase the risk of shortened telomere length in newborns and cardiovascular metabolic health damage in children, and has attracted attention from many researchers in recent years. This article reviewed recent studies both domestically and internationally on the associations among cadmium exposure during pregnancy, shortened telomere length in newborns, and cardiovascular metabolic abnormalities in children, and briefly outlined possible mechanisms of shortened telomere length in newborns by cadmium exposure during pregnancy. Current research results showed that cadmium exposure during pregnancy is related to shortened telomere length in newborns and cardiovascular metabolic abnormalities in children, and shortened telomere length in newborns is also related to cardiovascular metabolic abnormalities in children. It suggested that telomere length in newborns may be a biomarker reflecting cardiovascular metabolic abnormalities in children caused by cadmium exposure during pregnancy. In addition, the current potential mechanisms of cadmium exposure during pregnancy accelerating neonatal telomere length shortening include inflammatory reaction, mitochondrial dysfunction, antioxidant consumption/antioxidant enzyme inactivation, and DNA methylation, and these biological mechanisms are associated with cardiovascular metabolic abnormalities through certain factors, such as obesity, elevated blood pressure, impaired fasting blood glucose, and dyslipidemia in children, suggesting that cardiovascular metabolic abnormalities in children may be programmed in early life, but there are still few relevant studies. In the future, research should be conducted on the association among cadmium exposure during pregnancy, telomere length, and offspring cardiovascular metabolism, as well as possible mediating efficacy and related biological mechanisms of telomere length, aiming to provide early-life biological information for the prevention of cardiovascular and metabolic diseases.

Objective: To compare the differences in gut microbiome composition between children with good neurodevelopment and those with delayed neurodevelopment, and to analyze the relationship between gut microbiome and the neurodevelopment status of infants in early life., Methods: The mothers were included at the Second West China Hospital from November 2020 to April 2021. Their infant stools were collected on day 0 and day 90 after birth, and the follow-up questionnaires at the corresponding time points were completed. Additionally, the Ages and Stages Questionnaires-Third Edition(ASQ-3) were completed by mothers at 12 months of age. The structure and diversity of gut microbiota were examined by 16S rRNA sequencing, and the relationship between gut microbiome and ASQ-3 questionnaire scores in early life was analyzed., Results: According to the ASQ-3 scores, mothers and infants into neurodevelopment good group(G group, n=18) and neurodevelopmental delay group(D group, n=10). Compared with the D group, the relative abundance of the Firmicutes was significantly higher in the G group at day 0(P<0.05), while the level of the Proteobacteria was lower(P<0.05). At day 90 after birth, the relative abundance of the Actinobacteria, Bifidobacteriaceae and Enterococcaceae was significantly higher in the G group(P<0.05). In addition, alpha diversity was not statistically different between the two groups. Spearman's correlation analysis showed that Clostridiaceae of the postnatal day 0 infants was positively correlated with the communication domain score, but negatively associated with gross motor domain score in children at 12 months of age, whereas the relative abundance of Proteobacteria and Enterobacteriaceae of children at postnatal day 90 was negatively associated with communication development, while the relative abundance of Erysipelatoclostridiaceae showed a negative correlation with gross motor domain scores., Conclusion: The structure of the gut microbiome in early life between neurodevelopment good and delayed infants, and were associated with the development of communication and gross motor domain in infants at 12 months of age, suggesting that gut microbiome in early life may be related to the level of neurodevelopment in infants.

Early life nutrition plays an important role in determining the pregnancy outcomes and oflFspring lifeloi hcaldt Carotenoids deficiency is associated with adverse pregnancy outcomes such as preedampsia premature delivery and intrauterine growth restriction. Carotenoids possess antioxidant, inflammation modulating and immime-enhancmg properties and promote visual, cognitive and respiratory health in offsprings. Among carotenoids, a-carotene, P-carotene and P-cryptoxanthin can be transformed into vitamin A in vivo, and their conversion rates are affected by the nutritional status of vitamin A. Lutein and zeaxanthin are highly enriched in tike brain and Tctina of infents and young children, which arc closely related to the development of visual acuity and cognitive function. Breast milk contains an adequate level of lutein and its absorption rate is significantly higher than that of infant formulas. Consequently lutein supplementation is necessary for artificially fed infants, especially premature infants. In this paper, the functional research progresses of carotenoids related to adverse pregnancy outcomes and offspring development, as well as the present situation of carotenoids supplementation in formula were reviewed. [ABSTRACT FROM AUTHOR]

Accumulating evidences suggest that gut microbiota is associated with the development of obesity. Early life is a critical period for gut microbial colonization and development. Maternal vaginal flora and breast milk microbiota are important microbial sources for infant gut microbiota. In early life, the factors that influence the colonization and composition of gut microbiota include intrauterine microbial exposure, mode of delivery, type of infant feeding, antibiotic use, infant behavior and habits, geographical environment, and child genetic factors, etc. These factors may influence the development of childhood obesity via changing the composition of intestinal microbiota. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of famine-experience during early life on osteoporosis in adulthood. Methods A total of 3951 subjects born between 1956 and 1965 and attended the health examination at health screening center in 2013 were recruited. People born from 1956 to 1958 and from 1963 to 1965 were combined as control group. The prevalence of osteoporosis among subjects born from 1959 to 1962 and the controls was compared respectively. The effect of famine in early life on osteoporosis in adulthood was examined using a cumulative logistic regression model. Results The prevalence of osteoporosis among subjects born from 1956 to 1965 was 2. 18%. Prevalence of osteoporosis among subjects born in 1959, 1960, 1961, 1962, and the non-exposed group was 0. 84%, 1. 75%,3. 53%, 1. 62%, and 2. 32%, respectively. The prevalence of osteoporosis increased with the age (Z = 19. 95,P < 0. 001) and was significantly higher in males than in females (Z = 13. 3119,P < 0. 001). Results from the cumulative logistic regression analysis showed that experience of famine during early life had impact on osteoporosis in adulthood after adjustment of the other variables. The odds ratio was 0. 712 (95% CI: 0. 520- 0. 975,P = 0. 034) in people born in 1960, comparing with the control group. After stratification by gender, odds ratio in males born in 1960 and 1961 was 0. 569 (95% CI: 0. 374-. 868,P = 0. 009) and 1. 339 (95% CI: 1. 000- 1. 792,P = 0. 050), respectively. The odds ratio in females born in 1960 was 1. 012 (95% CI: 0. 639- 1. 601,P = 0. 961) after adjustment of the other variables. Conclusion Experience of famine during early life has impact on osteoporosis in adulthood and the effect mainly exists in males. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of using Bifidobacterium bifidum TMC3115 in early life on intestinal microbiota and immune functions and the long-term impact on inflammatory bowel disease., Methods: Fourteen pregnant BALB/c mice were purchased and 84 newborn BALB/c mice were subsequently obtained. Then, the newborn mice were randomly assigned to a normal saline (NS) group and a TMC3115 group, given via oral gavage normal saline and TMC3115, respectively, at a daily volume of 0.2 mL for each mouse. About 42 mice were assigned to each group. The gavage was stopped after 3 weeks. At this point, half of the mice in each group were sacrificed, and then the remaining mice in each group were randomly divided into NS-water group, NS-DSS group, TMC3115-water group, and TMC3115-DSS group, with about 10 mice in each group. The mice were given regular feed until the end of week 6 when they were given 3% dextran sulphate sodium (DSS) ad libitum for 4 days to establish the enteritis model, while the non-modeling groups were given pure water ad libitum . The experiment ended after 6 weeks and 4 days. The weekly body mass changes of the mice were documented. The intestinal tissue at the end of the experiment and the fecal samples, spleen and serum of the mice at 3 weeks and at the end of the experiment were collected to determine the pathology scores of colonic inflammation, the composition of fecal gut microbiota, spleen organ index and the mass concentration of serum cytokines., Results: 1) At the end of the experiment, the inflammatory pathology score was significantly lower in the TMC3115-DSS group compared with that of the Saline-DSS group ( P <0.05), with less disruption of colonic crypt structures and other structures, less inflammatory infiltration, and more intact epithelial structures. 2) At 3 weeks, in comparison with those of the NS group, the relative abundance of Bifidobacterium was significantly higher in the feces of the TMC3115 ( P <0.05), the relative abundance of both Enterococcus and Staphylococcus was lower ( P <0.05), the splenic organ index was significantly higher ( P <0.05), and interleukin (IL)-10 was significantly decreased ( P <0.05), while there was no significant change in IL-6 or TNF-α ( P >0.05). At the end of the experiment, in comparison with those of the NS-DSS group that undergone DSS induction, the TMC3115-DSS group had reduced relative abundance of Staphylococcus , Staphylococcus tumefaciens and Escherichia / Shigella in the feces ( P <0.05), while the splenic organ index was significantly higher ( P <0.05), and there were no significant changes in IL-6 or TNF-α ( P >0.05)., Conclusion: The use of TMC3115 in early life promotes the construction of gut microbiota in neonatal mice, thereby producing a long-term effect that alleviates colitis in mice, but the mechanisms involved are still not fully understood., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Objective: To explore the protective effect and mechanism of Bifidobacterium bifidum TMC3115 of improving the gut microbiota disorder caused by antibiotic exposurein early life, and the possible protection of inflammatory bowel disease in adulthood in mice., Methods: 80 newborn mice were randomly divided into 3 groups, a blank control group(n=40), a ceftriaxone exposure group(n=20), a Bifidobacterium bifidum TMC3115 intervention group(n=20). After birth, they were respectively treated with saline, ceftriaxone(100 mg/kg), and ceftriaxone(100 mg/kg) + TMC3115(1×10~9CFU/d) for 3 weeks. After 3 weeks, half of each group was randomly sacrificed, and the rest were normally fed to 6 weeks. At 6 weeks, the blank control group was randomly divided into a negative control group(n=10) and a colitis model group(n=10). The negative control group drunk pure water freely, and the other three groups were added 3% DSS to the drinking water for 4 days to induce colitis. At 6 weeks and 4 days, the remaining mice were sacrificed. The weight change, spleen coefficient, gut microbiota analysis based on second-generation sequencing and serum tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-10(IL-10)levels of the mice at 3 weeks and after DSS intervention were recorded. In addition, the colon length and inflammation pathology score of the mice after DSS intervention were also measured., Results: At 3 weeks, compared with the control, antibiotic exposure in the early life inhibited the weight gain and reduced the diversity and uniformity of the gut microbiota of the mice(P&lt;0.05). The intervention of TMC3115 under antibiotic exposure during this period increased the relative abundance of Bifidobacterium in the intestines(P&lt;0.05), and the effect still existed after DSS stimulation in adulthood, laying the foundation for TMC3115 to exert long-term benefits. After DSS stimulation in adulthood, mice showed significant weight gain inhibition, colon length shorteningand inflammation pathology scoreincrease compared with the negative control(P&lt;0.05), showed the inflammatory bowel disease(IBD)model was successfully constructed. The relative abundance of beneficial bacteria such as Lactobacillus in the Bifidobacterium bifidum TMC3115 intervention group increased compared with the ceftriaxone exposure group(P&lt;0.05), while the relative abundance of harmful bacteria such as Staphylococcus, Clostridium, and Desulfovibrio decreased(P&lt;0.05). Furthermore, the mice exposed to antibiotic in early life produced a stronger immune response, but the mice which received TMC3115 intervention at the same time had a significant decrease in serum TNF-α and IL-6 levels and increase in IL-10 level compared with the mice which only interfered with antibiotics(P&lt;0.05)., Conclusion: Antibiotic exposure in early life is a negative factor for long-term inflammatory bowel disease, and TMC3115 has preventive significance for long-term inflammatory bowel disease under the background of antibiotic exposure. The mechanism of TMC3115 may be to adjust the gut microbiota and balance the immune system.

Objective: This study aimed to explore whether exposure to ceftriaxone during early life could influences glucose and lipid metabolism of high fat diet-induced mice., Methods: Total 48 of female BALB/c aged 2 week old were randomly divided into control group(treated with saline), antibiotic group(treated with100 mg/kg ceftriaxone), high-fat diet group(treated with saline) and combined action group(treated with 100 mg/kg ceftriaxone)(n=12), respectively to stop gavage 2 weeks later. Then high-fat diet group and combined action group were fed with high-fat diet for 12 weeks. Fasting blood glucose(FBG) and oral glucose tolerance test were conducted in the last week. Serum total cholesterol(TC), triglyceride(TG), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), fasting insulin, leptin and TG, TC in liver were also measured. Furthermore, homeostasis model assessment of insulin resistance(HOMA-IR) was calculated from FBG and insulin., Results: Compared with normal chow diet, high-fat diet impaired oral glucose tolerance and increased the levels of abdominal adipose tissue, FBG, HOMA-IR, lips in serum and liver and leptin(P&lt;0. 05). The oral administration of ceftriaxone in early life impaired oral glucose tolerance and increased the levels of abdominal adipose tissue, FBG and TG in liver(P&lt;0. 05). In addition, early ceftriaxone intervention could enhance the impaired glucose tolerance, the increasing FBG, insulin resistance and liver lipids associated with high-fat diet(P&lt;0. 05)., Conclusion: Early ceftriaxone intervention not only significantly increases the level of abdominal adipose tissue, FBG, insulin resistance and liver lipids, but also enhances glycolipid metabolic disorders induced by high-fat diet. These result suggest that the exposure to antibiotics in the early life might increase the sensitivity of host animal to high fat diet induced abnormal glycolipid metabolism late.

Objective: To examine the associations between season of birth and factors as age at menarche, age at menopause and reproductive span. Methods: A total of 285 186 female from the China Kadoorie Biobank, with complete data on critical variables and had menarche at 9-18 years old, were included. A total of 132 373 female with natural menopause were included for the analysis on age at menopause and reproductive span. Multiple linear regression models were used to assess the associations of birth season and the age at menarche, menopause, and reproductive span. Subgroup analyses were performed on birth cohorts and urban/rural residence. Results: Compared with the Spring-born (March, April, and May), participants who were born in Summer (June, July, and August), Autumn (September, October, and November), and Winter (December, January, and February) appeared late on both age at menarche and menopause. Multivariable-adjusted coefficients (95 % CI ) appeared as 0.14 (95 % CI : 0.13-0.16), 0.26(95 % CI : 0.24-0.27), 0.10 (95 % CI : 0.08-0.12) for age at menarche respectively and 0.14 (95 %CI : 0.08-0.20), 0.18 (95 %CI : 0.12-0.24), 0.09 (95 %CI : 0.03-0.16) for age at menopause respectively. No statistically significant association was found between the season of birth and reproductive span. The association was consistent between urban and rural residents and across the birth cohorts. Conclusions: female born in spring showed both earlier age on both menarche and menopause, compared to the ones born in other seasons. Our findings suggested that exposures in early life with some degree of seasonal variation might influence the development of female reproductive system.