Theriome, Inc. Phoenix, AZ — Maternal deficiency in folic acid and choline alters stool metabolite profiles in offspring, signaling changes in gut microbiota and metabolic pathways. While stroke and brain injuries typically disrupt the gut, mice with maternal deficiencies in these two nutrients exhibited more severely disrupted gut biochemistry.
The effects were more pronounced in female offspring, highlighting potential sex-specific vulnerabilities in gut and brain biochemistry. This study, recently published in the journal Metabolites, suggests that maternal nutrient deficiencies increase the offspring's gut flora and brain vulnerability to damage such as stroke.
Subclinical preconception and prenatal nutrient deficiencies are common yet often overlooked, particularly in underserved ethnic groups and regions with health disparity and limited access to preconception and prenatal health screenings. These deficiencies can contribute to fertility and health issues in the offspring.
Alarmingly, in the US, one in three African-American and Mexican-American women don’t meet folic acid intake recommendations, and one in four American women fall short on choline consumption. Such disparities may lead to generational health impacts. These deficiencies do not show apparent symptoms or abnormal ranges in typical blood tests.
Both folic acid and choline are essential in one-carbon metabolism, while choline is a key building block for the brain. Maternal deficiencies of these nutrients can impact the long-term health of offspring, increasing the risk of diseases, such as metabolic issues or impairments to brain health. Also, most nutrition studies have historically focused on males, so many gender differences have remained uncovered.
Paniz Jasbi, PhD, and colleagues compared the stool metabolites of mice from healthy mothers and mothers deficient in folic acid or choline. Two-month-old female mice received folic-acid-deficient, choline-deficient, or control diets for four weeks. Subsequently, they were mated and received the same diet throughout pregnancy and lactation. Their offspring received an experimental ischemic stroke at two months of age. The researchers then profiled the stool metabolites before, one week after, and four weeks after the stroke.
Prior to the stroke, the offsprings' stool metabolites already exhibited significant differences. The offspring of nutrient-deficient mothers had less beneficial microbiome metabolites, suggesting a less healthy gut flora. At one week and four weeks post-stroke, the biochemical differences became more pronounced, suggesting that the maternal folic acid and choline deficiencies affect brain structure and resilience.
Most of the affected metabolites were involved in cell survival and developmental mechanisms, such as fat metabolism, amino acid pathways, cell division, energy metabolism, blood vessel health, immune responses, antioxidant responses, and neuroprotection. These pathways are crucial for brain health and resilience. For example, 7-dehydrocholesterol and homocitrulline—which are crucial for neuroprotection and inflammation regulation—were significantly reduced in the offspring of deficient mothers.
The overall metabolite levels were significantly lower at one week but returned to normal by four weeks after the stroke. Mice with maternal deficiencies had lower metabolites compared to those whose mothers had the control diet. Overall, daughters of deficient mothers were more adversely affected, emphasizing the potential gender differences in responses to transgenerational nutrient deficiencies.
These results underscore how maternal nutrient deficiencies can disrupt offspring metabolic pathways. In many cases, these adverse effects may not become apparent until after stressors, such as a stroke or other environmental challenges. These findings emphasize the importance of investigating sex-specific responses to maternal nutrition, a historically underexplored area in biomedical research.
Metabolomic tests like Theriome's Aristotle offer a critical solution by identifying nutrient deficiencies and the ripple biochemical effects not otherwise detectable through standard diagnostic blood tests. In addition, Theriome’s Aristotle identifies and recommends targeted food and supplement programs for prospective mothers to promote their children's health. Moreover, metabolomic studies, especially at a population level, can guide public health policy to prioritize prenatal nutrition through public health initiatives and accessible testing technologies.
About Theriome, Inc.
Theriome, Inc. is a biotech startup that delivers state-of-the-art omic tests, which derive health insights from entire sets of biological molecules. By testing metabolites in small blood samples, Theriome’s Aristotle test can accurately profile and analyze 68% of the human biochemical pathways.
By combining the measurements with artificial intelligence, Theriome makes it possible to identify biochemical deficiencies and disease signatures long before symptoms occur. Then, using Digital Twinning, the algorithm can recommend the best corrective course of action based on 1,000 simulations of all possible scenarios, given your test results and health history. In this context of prenatal nutrition, Theriome identifies and corrects invisible nutrient deficiencies that may affect your children’s health.
References:
Anwar, F., Mosley, M.-T., Jasbi, P., Chi, J., Gu, H. and Jadavji, N. M. (2024) Maternal dietary deficiencies in folic acid and choline change metabolites levels in offspring after ischemic stroke. Metabolites, 14, 552. https://doi.org/10.3390/metabo14100552