OBJECTIVES: The risk factors and role of mother‒child gut microbiota in pediatric inflammatory bowel disease (PIBD) remain unclear. We aimed to explore the clinical risk factors associated with PIBD, analyze the characteristics of gut microbiota of children and their mothers, and examine the correlation of the microbial composition in mother‒child pairs. METHODS: We conducted a case-control study including children with PIBD and their mothers as the case group, as well as healthy children and their mothers as the control group. Questionnaires were used to collect information such as family illness history and maternal and early-life events. Fecal samples were collected from the children and mothers for microbiota 16S ribosomal RNA (rRNA) sequencing to analyze the composition and its potential association with PIBD. RESULTS: A total of 54 pairs of cases and 122 pairs of controls were recruited. A family history of autoimmune disease and antibiotic use during pregnancy were associated with an increased risk of PIBD, and a higher education level of the father was associated with a decreased risk of PIBD. Children with PIBD and mothers exhibited different gut microbiota compared to healthy children and mothers. Similarities were observed in the gut microbiota of mothers and children in the same groups. Some bacterial biomarkers of mothers discovered in this study had the power to predict PIBD in their offspring. CONCLUSIONS PIBD is influenced by maternal risk factors and has unique gut microbiota characteristics. The mother‒child gut microbiota is closely related, suggesting the transmission and influence of the gut microbiota between mothers and children. This study highlights the potential pathogenesis of PIBD and provides a basis for developing targeted interventions.
Humans ; Gastrointestinal Microbiome ; Female ; Risk Factors ; Case-Control Studies ; Male ; Child ; Inflammatory Bowel Diseases/etiology* ; Adult ; RNA, Ribosomal, 16S/genetics* ; Feces/microbiology* ; Mothers ; Pregnancy ; Child, Preschool

Objective:To investigate the effects of maternal antibiotics during the pre-natal period on the develop-ment of microglia and anxiety-like behaviors in offspring.Methods:Female SD rats were randomly divided into a maternal control group(CON-M)and a maternal antibiotic group(ABX-M),with 5 rats in each group.The antibiotic group received oral administration of compound antibiotics for 7 days before conception,and the control group received oral administration of the same dose of 0.9％saline during the same period.Subsequently,the two groups of female rats completed the pregnancy and delivery process at the same time,and their male offspring were retained and marked as the offspring control group(CON-O)and the offspring antibiotic group(ABX-O),respectively.The anxiety-like behaviors of offspring rats at 4 weeks and 8 weeks of age were evaluated by open field test and elevated plus maze test,respectively.The number and morphology of microglia in the hippocampus(HIP),cingulate gyrus(CG)and basolater-al nucleus of amygdale(BLA)of the brain of each group of offspring rats were detected by laser confocal microscopy im-aging.Results:The body weight and number of offspring were reduced in the ABX-M group.The 4-week-old ABX-O group showed an increase in anxiety-like behaviors,accompanied by an increase in the number and immature phenotype of microglia in the hippocampus,cingulate gyrus,and amygdala.Compared with the 8-week-old CON-O group,the 8-week-old ABX-O group showed obvious anxiety-like behaviors,and the number and immature phenotype of microglia in the hippocampus,cingulate gyrus,and amygdala of the brain continued to increase.Conclusion:Maternal antibiotic exposure during the pre-pregnancy period significantly affects the number and maturation of microglia in offspring,lead-ing to anxiety-like behaviors,and its effects can persist into adulthood.

Objective:To investigate the effects of maternal antibiotics during the pre-natal period on the develop-ment of microglia and anxiety-like behaviors in offspring.Methods:Female SD rats were randomly divided into a maternal control group(CON-M)and a maternal antibiotic group(ABX-M),with 5 rats in each group.The antibiotic group received oral administration of compound antibiotics for 7 days before conception,and the control group received oral administration of the same dose of 0.9％saline during the same period.Subsequently,the two groups of female rats completed the pregnancy and delivery process at the same time,and their male offspring were retained and marked as the offspring control group(CON-O)and the offspring antibiotic group(ABX-O),respectively.The anxiety-like behaviors of offspring rats at 4 weeks and 8 weeks of age were evaluated by open field test and elevated plus maze test,respectively.The number and morphology of microglia in the hippocampus(HIP),cingulate gyrus(CG)and basolater-al nucleus of amygdale(BLA)of the brain of each group of offspring rats were detected by laser confocal microscopy im-aging.Results:The body weight and number of offspring were reduced in the ABX-M group.The 4-week-old ABX-O group showed an increase in anxiety-like behaviors,accompanied by an increase in the number and immature phenotype of microglia in the hippocampus,cingulate gyrus,and amygdala.Compared with the 8-week-old CON-O group,the 8-week-old ABX-O group showed obvious anxiety-like behaviors,and the number and immature phenotype of microglia in the hippocampus,cingulate gyrus,and amygdala of the brain continued to increase.Conclusion:Maternal antibiotic exposure during the pre-pregnancy period significantly affects the number and maturation of microglia in offspring,lead-ing to anxiety-like behaviors,and its effects can persist into adulthood.

Abnormal brain-gut interaction is considered the core pathological mechanism behind the disorders of gut-brain interaction (DGBI), in which the intestinal microbiota plays an important role. Microglia are the "sentinels" of the central nervous system (CNS), which participate in tissue damage caused by traumatic brain injury, resist central infection and participate in neurogenesis, and are involved in the occurrence of various neurological diseases. With in-depth research on DGBI, we could find an interaction between the intestinal microbiota and microglia and that they are jointly involved in the occurrence of DGBI, especially in individuals with comorbidities of mental disorders, such as irritable bowel syndrome (IBS). This bidirectional regulation of microbiota and microglia provides a new direction for the treatment of DGBI. In this review, we focus on the role and underlying mechanism of the interaction between gut microbiota and microglia in DGBI, especially IBS, and the corresponding clinical application prospects and highlight its potential to treat DGBI in individuals with psychiatric comorbidities.
Humans ; Gastrointestinal Microbiome ; Irritable Bowel Syndrome/therapy* ; Microglia ; Brain Diseases ; Brain

Background/Aims: Irritable bowel syndrome (IBS) is accepted as a disorder of gut-brain interactions. Berberine and rifaximin are non-absorbed antibiotics and have been confirmed effective for IBS treatment, but there is still lack of direct comparison of their effects. This study aims to compare the effect of the 2 drugs on the alteration of gut-brain axis caused by gut microbiota from IBS patients. Methods: Germ-free rats received fecal microbiota transplantation from screened IBS patients and healthy controls. After 14 days’ colonization, rats were administrated orally with berberine, rifaximin or vehicle respectively for the next 14 days. The visceral sensitivity was evaluated, fecal microbiota profiled and microbial short chain fatty acids were determined. Immunofluorescence staining and morphological analysis were performed to evaluate microglial activation. Results: Visceral hypersensitivity induced by IBS–fecal microbiota transplantation was relieved by berberine and rifaximin, and berberine increased sucrose preference rate. Microbial α-diversity were reduced by both drugs. Compared with rifaximin, berberine significantly changed microbial structure and enriched Lachnoclostridium. Furthermore, berberine but not rifaximin significantly increased fecal concentrations of acetate and propionate acids. Berberine restored the morphological alterations of microglia induced by dysbiosis, which may be associated with its effect on the expression of microbial gene pathways involved in peptidoglycan biosynthesis.Rifaximin affected neither the numbers of activated microglial cells nor the microglial morphological alterations. Conclusions Berberine enriched Lachnoclostridium, reduced the expression of peptidoglycan biosynthesis genes and increased acetate and propionate. The absence of these actions of rifaximin may explain the different effects of the drugs on microbiota-gut-brain axis.