Related Experiment Video
Updated: Jun 21, 2025
Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants
Published on: March 6, 2018
Distinct gut flora profile induced by postnatal trans-fat diet in gestationally bisphenol A-exposed rats
Sarah Zulkifli1, Noor Shafina Mohd Nor1,2,3, Siti Hamimah Sheikh Abdul Kadir1,4
1Institute for Pathology, Laboratory and Forensic Medicine (I-PPerForM), Faculty of Medicine, Universiti Teknologi MARA (UiTM) Sungai Buloh Campus, Selangor, Malaysia.
Insights
Postnatal trans fat diet significantly alters offspring gut microbiome, overshadowing prenatal BPA exposure effects. This dietary shift may lead to future metabolic health issues.
Area of Science:
- Environmental Health
- Microbiology
- Toxicology
Background:
- Prenatal exposure to Bisphenol A (BPA) and postnatal high-fat diets (HFD) are linked to adverse offspring health outcomes.
- Limited data exists on the interactive effects of prenatal BPA and postnatal diets on the gut microbiome.
Purpose of the Study:
- To investigate the impact of a postnatal trans fat diet (TFD) on the gut microbiome of offspring prenatally exposed to BPA.
- To determine whether postnatal diet or prenatal BPA exposure is the primary driver of gut microbiome alterations.
Main Methods:
- Pregnant rats were exposed to BPA or vehicle, and their offspring were fed either a normal diet (ND) or a TFD.
- Fecal samples were collected at days 50 and 100 for gut microbiome analysis using next-generation sequencing.
- Alpha and beta diversity, hierarchical clustering, network analysis, and differential species abundance (DESeq2) were employed.
Main Results:
- Trans fat diet (TFD) significantly reduced alpha diversity in offspring, irrespective of prenatal BPA exposure, compared to the normal diet (ND) group.
- Beta diversity analyses revealed distinct microbiome compositions between TFD and ND groups, with TFD groups showing greater differences.
- Differential species analysis indicated that postnatal diet had a more pronounced effect on gut flora composition than prenatal BPA exposure.
Conclusions:
- Postnatal diet, specifically TFD, appears to be a more significant factor than prenatal BPA exposure in shaping the gut microbiome of rat offspring.
- Altered gut flora in TFD offspring suggests potential perturbations in metabolic functions and epigenetic modifications.
- These changes may predispose offspring to metabolic diseases later in life, warranting further investigation.
Abstract:
There has been much evidence showing the repercussions of prenatal bisphenol A (BPA) exposure with a postnatal high fat-diet (HFD) on offspring's health. However, the information on how the interaction between these two variables affects the gut microbiome is rather limited. Hence, we investigated the impact of a postnatal trans fat diet (TFD) on the gut microbiome of offspring exposed to BPA during the prenatal period in an animal model. Pregnant rats were divided into 5 mg/kg/day BPA, vehicle Tween80 (P80) or control (CTL) drinking water until delivery (N = 6 per group). Then, weaned male pups were further subdivided into three normal diet (ND) groups (CTLND, P80ND, and BPAND) and three TFD groups (CTLTFD, P80TFD, and BPATFD) (n = 6 per group). 180-250 g of faecal samples were collected on days 50 and 100 to assess the composition of the offspring's intestinal flora using next-generation sequencing. The alpha diversity indices of TFD offspring with and without BPA were markedly lower than their ND counterparts (p<0.001-p<0.05). The beta diversity, hierarchical cluster and network analyses of the offspring's microbiome demonstrated that the microbiome species of the TFD group with and without BPA were distinctly different compared to the ND group. Consistently, TFD and ND offspring pairings exhibited a higher number of significantly different species (p<0.0001-p<0.05) compared to those exposed to prenatal BPA exposure and different life stages comparisons, as shown by the multivariate parametric analysis DESeq2. Predictive functional profiling of the offspring's intestinal flora demonstrated altered expressions of genes involved in metabolic pathways. In summary, the gut flora composition of the rat offspring may be influenced by postnatal diet instead of prenatal exposure to BPA. Our data indicate the possibility of perturbed metabolic functions and epigenetic modifications, in offspring that consumed TFD, which may theoretically lead to metabolic diseases in middle or late adulthood. Further investigation is necessary to fully understand these implications.
