High Fructose Intake During Pregnancy in Rats Influences the Maternal Microbiome and Gut Development in the Offspring

Abstract

Studies in pregnant women indicate the maternal microbiome changes during pregnancy so as to benefit the mother and fetus. In contrast, disruption of the maternal microbiota around birth can compromise normal bacterial colonisation of the infant’s gastrointestinal tract. This may then inhibit development of the gut so as to increase susceptibility to inflammation and reduce barrier function. The impact of modulating fructose intake on the maternal microbiome through pregnancy is unknown, therefore we examined the effect of fructose supplementation on the maternal microbiome together with the immediate and next generation effects in the offspring. Wistar rat dams were divided into control and fructose fed groups that received 10% fructose in their drinking water from 8 weeks of age and throughout pregnancy (10–13 weeks). Maternal fecal and blood samples were collected pre-mating (9 weeks) and during early (gestational day 4–7) and late pregnancy (gestational day 19–21). We show supplementation of the maternal diet with fructose appears to significantly modulate the maternal microbiome, with a significant reduction in Lactobacillus and Bacteroides. In offspring maintained on this diet up to pregnancy and term there was a reduction in gene expression of markers of gut barrier function that could adversely affect its function. An exacerbated insulin response to pregnancy, reduced birth weight, but increased fat mass was also observed in these offspring. In conclusion dietary supplementation with fructose modulates the maternal microbiome in ways that could adversely affect fetal growth and later gut development.

Fructose-Induced Intestinal Microbiota Shift Following Two Types of Short-Term High-Fructose Dietary Phases

“…The microbiota changes we observed at the phylum level are consistent with these data and also in agreement with our own previous findings that a high-fructose diet caused a reduced Bacteroidetes abundance and a slightly enhanced Firmicutes abundance [ 6 ]. Furthermore, our data are in accordance with a study by Astbury et al [ 46 ], who found a higher Firmicutes and a lower Bacteroides abundance after a high-fructose diet during pregnancy in rats. However, it should be noted that all these studies analyzed the effects of fructose either added to the solid diet or as an additive in drinking water, but not as fructose from whole fruits.…”

“…These results are consistent with findings from our own group demonstrating that Parabacteroides abundance was reduced after a high-fructose diet [ 6 ]. Our observations align with a previous report in which Parabacteroides species were exclusively observed in rats fed a control diet and not in a fructose-rich diet [ 46 ]. Recently, the gut commensal Parabacteroides distasonis was shown to alleviate obesity [ 74 ] further strengthening the assumption that a high-fructose diet hampers health promoting microbiota and might thus promote metabolic diseases.…”

The Impact of Maternal Pre-Pregnancy Body Weight and Gestational Diabetes on Markers of Folate Metabolism in the Placenta

“…It is possible that other adaptations to a high pre-pregnancy BMI, such as hormonal changes in pregnancy and endocrine modifications, could contribute [ 6 ]. It is possible that adaptations within the maternal microbiome could impact on maternal folate status [ 32 ], as has been shown in the rat during late gestation when manipulating macronutrient intake [ 33 ]. Interestingly, obesity with GD resulted in raised placental MTHFR gene expression that could ultimately inhibit intracellular homocysteine release by promoting 5-MTHF synthesis [ 34 , 35 , 36 ].…”

Organismal Fructose Metabolism in Health and Non-Alcoholic Fatty Liver Disease

“…One emerging development in the field of fructose metabolism is the role of the gut microbiota. Recent breakthroughs in meta-genome sequencing and metabolomics technologies have identified the link between differential gut microbiota subpopulations and their metabolic products in the context of NAFLD [ 28 , 64 , 65 , 66 ]. Because the small intestinal fructose absorption is limited [ 38 ], high-dose fructose readily reaches the large intestine and induces bacterial fermentation [ 67 , 68 , 69 , 70 ].…”

“…For example, the fecal sequencing of rats on high-fructose diets displayed a marked increase in Bacteroidetes:Firmicutes ratios [ 70 ]. On the other hand, a similar study with pregnant rats suggested decreased Bacteroidetes levels [ 65 ]. In humans, an overrepresentation of several species of Firmicutes was found in a study involving obese individuals [ 69 ].…”