Effects of maternal obesity and direct exposure to high-fat diet on bowel functions in offsprings

BACKGROUND and AIM: The prevalence of overweight and obesity in children and among women in reproductive age has increased substantially representing a critical issue. Because maternal obesity is known to exert detrimental consequences on offspring, this study investigated the impact of maternal obesity and high-fat diet exposure on offspring gastrointestinal (GI) system.METHODS: C57BL/6J female mice were fed with standard (SD) or high-fat (HFD) diet for 8 weeks, mated with SD males and exposed to SD or HFD throughout pregnancy and lactation. At weaning, pups were randomly assigned to SD or HFD for 8 weeks. Body weight and food intake were monitored once a week. Blood glucose, triglycerides, cholesterol, insulin and leptin levels and faecal pellet expulsion frequency were evaluated the day before sacrifice. Interleukins levels were assayed by ELISA. GI transit was assessed after intragastric administration of non-absorbable fluorescein isothiocyanate labelled dextran (FITC-dextran 70 kDa). Intestinal permeability was determined by plasma level assessment of low molecular weight FITC-dextran and zonulin-1 by ELISA. Immunofluorescence staining for the neuronal (HuC/D), neuronal nitric oxide synthase (nNOS) and glial (S100β) markers was evaluated in longitudinal muscle myenteric plexus preparations of ileum. The microbiota composition of colonic faecal pellets was analysed by 16rRNA amplicon sequencing. RESULTS: HFD pups developed increased body weight and metabolic indexes, decreased food intake and changes in microbiota (increased abundance of Firmicutes and Proteobacteria and reduction of Bacteroidetes) irrespectively of the maternal diet. They also displayed an increment in serum IL-1β, IL-23, IL-6 and a decrease in IL- 10 levels, more pronounced in female and male pups born to obese dams and fed with SD. HFD female pups showed a delay in GI transit, more severe in those born to HFD mothers, confirmed by a reduction of stool expulsion frequency. Male pups born from SD dams and fed with HFD displayed both a delay in GI transit and a decrease in faecal pellet expulsion, more severe in those born from HFD dams and fed with SD. The increase in intestinal permeability, observed in HFD offspring, was further enhanced in pups born from obese mothers. Staining for HuC/D and nNOS was decreased in both sexes fed with HFD and among the offspring born from HFD mothers; these changes were more pronounced in SD pups. The immunoreactivity to S100β was increased in HFD pups but was reduced in pups born from obese dams. CONCLUSION: Body weight gain, alterations of metabolic parameters and changes in microbiota occur mainly in offspring with direct exposure to HFD. Maternal HFD consumption confers to the offspring a higher susceptibility to develop bowel dysfunctions and among the offspring from obese dams; the most detrimental impact was observed in pups fed with SD.