[Relationship between gut microbiome and neurodevelopment in early life].

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.

[Influence of different fecal microbiota transplantation cycles on the recovery of intestinal microbiota in the antibiotic cocktail-pretreated mice].

OBJECTIVE: To explore the effects of different transplantation frequencies and time of fecal microbiota transplantation on mice. METHODS: Twenty-four C57BL/6J mice were randomly divided into control group, fecal microbiota transplantation group 1(FMT1), fecal microbiota transplantation group 2(FMT2), and fecal microbiota transplantation group 3(FMT3). The control group was used as the donor of fecal microbiota transplantation, and the FMT1, FMT2, and FMT3 groups were intervened with mixed antibiotics(200 µL/d) for 2 weeks, and received fecal bacterial suspension(200 µL/d). The transplantation time of the FMT1 group frequency was 1 time/d for 1 weeks, the FMT2 group was 1 time/d for 2 weeks, and the FMT3 group was 3 times/week for 2 weeks. At the end of the experiment, the feces of the mice were collected to analyze the gut microbiota. RESULTS: Compared with the control group, there were more independent Amplicon Sequence Variants in the intestinal microbiota of mice in FMT1 group, FMT2 group and FMT3 group, and the ACE index and Chao1 index were significantly reduced(P<0.05). Beta diversity showed differences between fecal microbiota transplantation and control groups, with FMT2 and control groups being the closest. At the phylum level, there were two species in FMT1 group and one species in FMT3 group showed statistically significant differences compared with control group(P<0.05). However, there was no significant difference between the FMT2 group and the control group. At the genus level, there were 6 species in the FMT1 with statistically significant differences from the control group(P<0.05), and 2 species in the FMT2, 5 species in the FMT3 respectively. Among which FMT2 group has the least number of species that differed from the control group, suggesting that the compitsition of its intestinal microbiota is closet to that of the control group. CONCLUSION: Fecal bacteria transplantation helps to restore the intestinal microbiota structure of mice cleaned by antibiotics, and different transplantation frequencies and transplantation times have different recovery effects on the intestinal microbiota of mice pretreated with antibiotics, and the fecal bacteria transplantation effect is better with 1 time/d lasting 2 weeks.

Live and Heat-Inactivated Streptococcus thermophilus MN-ZLW-002 Mediate the Gut-Brain Axis, Alleviating Cognitive Dysfunction in APP/PS1 Mice.

Research on regulating brain functions with probiotics and postbiotics through the gut-brain axis is attracting attention, offering the possibility of adjuvant therapy for Alzheimer's disease (AD). Three-month-old male APP/PS1 mice were gavaged with live and heat-inactivated S. thermophilus MN-002 for three months. This study demonstrated that live and heat-inactivated S. thermophilus MN-002 improved cognitive dysfunctions in APP/PS1 mice, especially in spatial memory. However, the main effects of live S. thermophilus MN-002 directly altered the intestinal microbiota composition and increased serum IL-1ß and IL-6. Heat-inactivated S. thermophilus MN-002 increased colonic propionic acid levels and enhanced the hippocampus's antioxidant capacity. Furthermore, the changes were more obvious in the high-dose group, such as astrogliosis in the hippocampus. These results indicate that different forms and doses of the same strain, S. thermophilus MN-002, can partly improve cognitive functions in AD model mice via the gut-brain axis.

Gut Microbiota Perturbation in Early Life Could Influence Pediatric Blood Pressure Regulation in a Sex-Dependent Manner in Juvenile Rats.

The present study aimed to investigate whether gut dysbiosis induced by ceftriaxone in early life could influence pediatric blood pressure regulation in childhood with or without exposure to a high-fat diet (HFD). Sixty-three newborn pups of Sprague-Dawley rats were administered ceftriaxone sodium or saline solution until weaning at 3 weeks, and the rats were fed a HFD or regular diet from 3 to 6 weeks. Tail-cuff blood pressure, the expression levels of genes of the renin-angiotensin system (RAS), the concentrations of IL-1ß, IL-6, and TNF-α in the colon and prefrontal cortex, and the composition of fecal microbiota were analyzed. Ceftriaxone treatment significantly increased the diastolic blood pressure of male rats at 3 weeks. At 6 weeks, systolic blood pressure (SBP) was significantly increased only in ceftriaxone treated male rats fed with HFD. The RAS showed increased activation in the kidney, heart, hypothalamus, and thoracic and abdominal aorta of male rats, but only in the kidney, heart, and hypothalamus of female rats. HFD-fed female rats showed a decreased level of IL-6 in the colon. α diversity of gut microbiota decreased and the Firmicutes to Bacteroidetes ratio increased in both male and female rats at 3 weeks; however, these parameters recovered to various degrees in female rats at 6 weeks. These results revealed that early-life gut dysbiosis induced by antibiotics combined with a HFD in childhood could be involved in pediatric blood pressure regulation and an increase in SBP in juvenile rats, and these effects occurred in a sex-dependent manner.