The Invisible Beginning
Similar to genetics, most look at their immune system as the cards they were simply dealt in life. Either good or bad, the immune system is a gift or a scourge of inheritance. How many times have you heard, “I wish I had a metabolism like that person”? The implication is that a thin person has the perfect metabolism. Moreover, the impact potential to influence immune system priming during pregnancy, birth, and in the early months post-delivery is lost on most, including scientists and medical practitioners. Both the maternal gut microbiome and the developing child’s gut microbiome are fertile soil to modulate to promote health or to disrupt and damage to promote disease.
Pregnancy and maternal nutrition are the keys to immune engineering. Immune engineering is immune priming—the earliest immune system setup. Such an early and critical impact should not be glossed over. Immune engineering primes the immune system from the very beginning to a lifetime of either increased potential for health or one of disease that lasts the entirety of the individual’s life. Think of it as an investment that can yield tremendous dividends.
Most look at lifestyle choices as potential positive or negative personal impacts: lifestyle choices impact the individual’s life only. In pregnancy, maternal diet does not just impact the mother, but it is the beginning of the immune engineering of their child. This immune engineering by maternal nutrition initiates the immune bias of their child prior to birth.
How?
Of course, there are multiple vectors by which diet, whether poor or good, impacts the immune system of the child during pregnancy, delivery, and the postpartum period. Yet, the gut microbiome, gut metabolome, and associated metabolites are key in the immune engineering and immune bias of the child. And it all begins in utero.
The Maternal Diet Biological Pipeline
First, I want to look at the impact of a maternal Mediterranean diet. Biology is not simply a sequence of steps. We break down complex information and problems into compartments (reductionism) to understand, but we must resynthesize the compartments back to the whole of biology—holism. I’ll use the same breakdown and resynthesis here.
Fortunately, the science is not speculative but very solid here. Maternal diet shapes the maternal gut microbiome in real time. Higher intake of fiber plus polyphenols increases specific gut taxa: Bifidobacterium, Faecalibacterium, Roseburia, and Akkermansia. Absence of these bacteria leaves the immune system unprimed for appropriate development, surveillance, and maturation to provide effective lifelong immunity. In addition, there is an overall increase in alpha diversity. The altered maternal gut microbiome does not exist in a bubble; it alters the gut metabolome. The microbiome produces metabolites (SCFAs, bile acids, and indoles) that cross the placenta to engage with the developing baby’s immune system in utero. The SCFAs produced include butyrate, acetate, and propionate. As a result of transplacental passage of gut metabolites, the developing baby’s immune cells are initially calibrated. It is the earliest stage of immune engineering, immune priming, and immune bias. And all that is in utero. During vaginal delivery, the altered maternal gut microbiome and metabolome are vertically transferred to the child—passing the seeds to the primed infant gut soil. Cesarean birth transfers a different gut microbiome, which is a topic for another post.
Following birth, the next seed of immune engineering is when breast milk completes the initial stages of immune training.
Building Immune Resilience and Early Immune Bias
Maternal nutrition engineers the immune system through interface with the gut microbiome and metabolome. Maternal diet directly influences the gut microbiome, which dictates the gut metabolome that translates directly to immune effects. Maternal diet is effectively prenatal immune engineering through gut ecosystem remodeling—immune tone. Remember, here we are focusing on the benefits of the maternal Mediterranean diet on pregnancy and early immune priming. Most focus on diet, here maternal diet, as calories and macronutrients, but its greatest impacts include immune priming and the lingering impact on health and disease. Aging and chronic diseases of aging, including cancer, begin in the gut microbiome and are directed by immune priming. It begs the question of whether aging and cancer is a choice?
Functionally, the specifics are well published:
• ↑ fetal Treg programming
• ↓ pro-inflammatory cytokine tone (IL-6 / TNF-α axis)
• Bias away from Th17 dominance
• Early innate immune priming—immune engineering
The result is in utero fetal immune development that is biased toward controlled responsiveness, non-inflammatory, and not hyper-reactive—a mature and balanced immune system.
Take home: Immune “tone” is already being shaped before birth, shaped largely by maternal microbiome–derived metabolites rather than nutrients, calories, and macronutrients alone.
Mediterranean Microbiome Metabolite Immune Engineering Benefits
Early maternal in utero priming through the gut microbiome engineers the immune system for immune balance and health. Pregnancy cohorts and birth studies reflect the reality of early health immune engineering:
• ↓ Childhood wheeze, eczema, and atopy risk
• ↓ Early-life systemic inflammatory markers (CRP, IL-6)
• Early and healthier infant microbiome trends (higher bifidobacteria; greater diversity by 6–12 months)
• Improved metabolic immune signaling (evident in improved insulin sensitivity markers later in childhood)
All this impact discussion just included the impact of the maternal Mediterranean gut microbiome shift and the in utero immune engineering from the transfer of the gut metabolome across the placenta to the developing immune system of the baby.
Let me wrap this post up by circling back around to the impact on future disease—cancer. The early and prolonged immune tone preserves epithelial barrier integrity and function, improves immune surveillance, reduces systemic endotoxemia, lowers basal inflammation, and promotes metabolic homeostasis. Lifelong education of our children begins early, in fact, in utero, and lasts an entire immune lifetime.
References
Chatzi, L., Torrent, M., Romieu, I., Garcia-Esteban, R., Ferrer, C., Vioque, J., Kogevinas, M., & Sunyer, J. (2008).
Mediterranean diet in pregnancy is protective for wheeze and atopy in childhood.
Thorax, 63(6), 507–513.
https://doi.org/10.1136/thx.2007.081745
Meiners, F., Ortega-Matienzo, A., Fuellen, G., & Barrantes, I. (2025).
Gut microbiome-mediated health effects of fiber- and polyphenol-rich dietary interventions.
Frontiers in Nutrition, 12, 1647740.
https://doi.org/10.3389/fnut.2025.1647740
Chatzi, L., Roumeliotaki, T., Garcia-Esteban, R., Basterrechea, M., Begiristain, H., Iñiguez, C., Vioque, J., Kogevinas, M., & Sunyer, J. (2013).
Mediterranean diet adherence during pregnancy and risk of wheeze and eczema in the first year of life: INMA (Spain) and RHEA (Greece) mother-child cohort studies.
British Journal of Nutrition, 110(11), 2058–2068.
https://doi.org/10.1017/S0007114513001426
Bédard, A., Northstone, K., Henderson, A. J., & Shaheen, S. O. (2020).
Mediterranean diet during pregnancy and childhood respiratory and atopic outcomes: A birth cohort study.
European Respiratory Journal, 55(3), 1901215.
https://doi.org/10.1183/13993003.01215-2019
Zhang, Y., Lin, J., Fu, W., Liu, S., Gong, C., & Dai, J. (2019).
Mediterranean diet during pregnancy and childhood for asthma in children: A systematic review and meta-analysis of observational studies.
Pediatric Pulmonology, 54(7), 949–961.
https://doi.org/10.1002/ppul.24338
Ferretti, P., Pasolli, E., Tett, A., Asnicar, F., Gorfer, V., Fedi, S., Armanini, F., Truong, D. T., Manara, S., Zolfo, M., Beghini, F., Bertorelli, R., De Sanctis, V., Bariletti, I., Canto, R., Clementi, R., Cologna, M., Crifò, T., Cusumano, G., … Segata, N. (2018).
Mother-to-infant microbial transmission from different body sites shapes the developing infant gut microbiome.
Cell Host & Microbe, 24(1), 133–145.e5.
https://doi.org/10.1016/j.chom.2018.06.005
Flores-Ventura, E., Esteban-Torres, M., Gueimonde, M., van Sinderen, D., Koren, O., & Hall, L. J. (2025).
Mother-to-infant vertical transmission in early life: A systematic review and proportional meta-analysis of Bifidobacterium strain transmissibility.
npj Biofilms and Microbiomes, 11, 121.
https://doi.org/10.1038/s41522-025-00720-y
Furusawa, Y., Obata, Y., Fukuda, S., Endo, T. A., Nakato, G., Takahashi, D., Nakanishi, Y., Uetake, C., Kato, K., Kato, T., Takahashi, M., Fukuda, N. N., Murakami, S., Miyauchi, E., Hino, S., Atarashi, K., Onawa, S., Fujimura, Y., Lockett, T., … Ohno, H. (2013).
Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells.
Nature, 504(7480), 446–450.
https://doi.org/10.1038/nature12721
Nakajima, A., Habu, S., Kasai, M., Okumura, K., Ishikawa, D., Shibuya, T., Osada, T., Watanabe, S., & Nagahara, A. (2020).
Impact of maternal dietary gut microbial metabolites on an offspring’s systemic immune response in mouse models.
Bioscience of Microbiota, Food and Health, 39(2), 33–38.
https://doi.org/10.12938/bmfh.19-013
Gray, L. E. K., O’Hely, M., Ranganathan, S., Sly, P. D., & Vuillermin, P. (2017).
The maternal diet, gut bacteria, and bacterial metabolites during pregnancy influence offspring asthma risk.
Frontiers in Immunology, 8, 365.
https://doi.org/10.3389/fimmu.2017.00365
Ryan, F. J., Clarke, M., Lynn, M. A., et al. (2025).
Early-life Bifidobacterium colonization supports optimal infant vaccine responses.
Nature, 641(8062), 456–464.
https://doi.org/10.1038/s41586-025-08796-4
