Exposure to caffeine during pregnancy, combined with a high-fat diet after birth, significantly increases the risk of autism-like behaviors in rodents, according to new research published in Ecotoxicology and Environmental Safety. This increased risk is related to changes in gut bacteria and increased levels of a specific immune molecule, IL-17A. The findings shed light on the relationships between diet, prenatal environmental exposures, and neurodevelopmental disorders.
The motivation behind this new study stems from a growing concern over the effects of prenatal caffeine exposure and high-fat diets on the developing brain. Previous research had already established a link between prenatal caffeine exposure and reduced fetal growth, with emerging evidence suggesting an increased risk of neurodevelopmental disorders like autism spectrum disorder (ASD).
ASD is a complex developmental condition that involves persistent challenges in social interaction, speech and nonverbal communication, along with restricted and repetitive behaviors. Given the widespread consumption of caffeine and the prevalence of high-fat diets, understanding these potential risk factors is crucial for developing strategies to prevent ASD.
“Most autism research focuses on genetic factors, overlooking autism caused by adverse prenatal environments and postnatal secondary impacts, known as fetal-origin autism. Investigating this area is not only a pressing scientific question but also essential to raising awareness about healthy childbearing and preventing negative prenatal environmental exposures,” said study author Dan Xu, an associate dean of the School of Pharmaceutical Sciences and professor of pharmaceutical sciences at Wuhan University.
In the study, pregnant rats were divided into two groups: one exposed to caffeine during a critical period of gestation, aiming to simulate prenatal caffeine exposure, and a control group receiving a placebo. This setup was intended to create a scenario where offspring would either be born under normal conditions or present with intrauterine growth retardation (IUGR), a condition linked to increased ASD risk.
Following birth, the offspring were subjected to further categorization based on their diet, receiving either a standard diet or a high-fat diet from postnatal week 4 onwards. This division allowed the team to assess the combined effects of prenatal caffeine exposure and postnatal dietary habits on the likelihood of developing ASD-like behaviors.
The researchers conducted a variety of tests and analyses to gauge the impact on the offspring. Behavioral tests were conducted to identify ASD-like behaviors, including social interaction tests and memory challenges. Additionally, the study investigated the biological mechanisms potentially driving the observed behaviors by analyzing gut microbiota and examining synaptic structures in the hippocampus, a brain area crucial for learning and memory.
Male offspring exposed to prenatal caffeine displayed typical ASD-like behaviors, while females showed reduced exploration and spatial memory. However, when exposed to a high-fat diet, both male and female rats exposed to prenatal caffeine exhibited exacerbated ASD-like behaviors.
“We found that male rats exposed to adverse prenatal environments exhibited autistic behaviors, but both male and female rats showed typical autism behaviors after being fed a high-fat diet post-birth,” Xu told PsyPost. “This suggests that attention should also be given to female offspring exposed to adverse prenatal environments.”
Further analysis revealed a damaged intestinal mucus barrier and significant changes in the gut microbiota, particularly an increased abundance of Escherichia coli (E. coli). This microbial shift was linked to an induced differentiation of colonic Th17 cells, leading to elevated levels of IL-17A. This cytokine, known for its role in inflammation, was found to traverse into the brain, causing synaptic damage in hippocampal neurons, a process the researchers identified as a pivotal factor in the development of ASD.
A strain transplantation experiment confirmed the pivotal role of E. coli in this process. Offspring rats receiving E. coli demonstrated enhanced ASD-like behaviors and increased IL-17A levels, underscoring the bacteria’s contribution to the disorder’s pathogenesis. This evidence points to the gut-brain axis as a critical pathway through which prenatal caffeine exposure and a postnatal high-fat diet may contribute to the risk of ASD.
“The study emphasizes that exposure to adverse prenatal environments (like high caffeine levels) and a high-fat diet post-birth are potential risk factors for autism,” Xu explained. “Avoiding these harmful environments and ensuring the stability of the gut-brain axis are crucial to mitigating the development of fetal-origin autism.”
“People should understand the significant role of gut microbiota in fetal-origin autism and the importance of maintaining a healthy diet post-birth, especially for infants exposed to adverse prenatal environments, to ensure a balanced gut microbiome.”
While the study marks a significant step forward in understanding the environmental factors contributing to ASD, the researchers acknowledge certain limitations. For instance, the study’s focus on a rat model means that further research is necessary to confirm these findings in humans. The study also highlights the need to explore the potential for gender-specific differences in the development of ASD, urging a closer look at the biological mechanisms at play.
“Although our study highlights gender differences in fetal-origin autism, further elucidation of its mechanisms is needed,” Xu said. “Future exploration of these gender differences will deepen our understanding of fetal-origin autism.”
The study, “Prenatal caffeine exposure induces autism-like behaviors in offspring under a high-fat diet via the gut microbiota-IL-17A-brain axis,” was authored by Tingting Wang, Shuai Zhang, Mingcui Luo, Mengxi Lu, Liyi Wei, Xinli Zhou, Hui Wang, and Dan Xu.