Plant-based fibre is broken down in the gut by bacteria into factors that influence the immune system. Researchers from the University of Sydney's Charles Perkins Centre, the Barwon Infant Study from Deakin University, Monash University, James Cook University and the Australian National University collaborated to investigate the role of these metabolic products of gut bacteria during pregnancy.
The study, published in Nature Communications, found that in humans, reduced levels of acetate, which is mainly produced by fibre fermentation in the gut, is associated with the common and serious pregnancy-related condition preeclampsia.
Senior author of the study Professor Ralph Nanan, from the University of Sydney School of Medicine and Charles Perkins Centre, said the simple recommendation to 'eat real food, mostly plants, and not too much' might be the most effective primary prevention strategy for some of the most serious conditions of our time.
The study found that preeclampsia affected the development of an important fetal immune organ, the thymus, which sits just behind the breastbone. Fetuses in preeclamptic pregnancies were found to have a much smaller thymus than children from healthy pregnancies.
The cells the thymus normally generates, called T cells (thymus-derived cells) - specifically those associated with the prevention of allergies and autoimmune conditions such as diabetes - also remained lower in infants after preeclampsia, even four years after delivery.
The mechanisms of acetate on the developing fetal immune system were further examined in separate experiments involving mice that showed acetate was central in driving fetal thymus and T cell development.
Autoimmune conditions explained?
Together, these results showed that promoting specific metabolic products of gut bacteria during pregnancy might be an effective way to maintain a healthy pregnancy and to prevent allergies and autoimmune conditions later in life.
The researchers argue that they may also, in part, explain the rapid increase of allergies and autoimmune conditions as Western diets are increasingly dominated by highly processed foods, which are very low in fibre.
Co-author Peter Vuillermin, co-lead of the Barwon Infant Study, a major birth cohort study being conducted by the Child Health Research Unit at Barwon Health, said: "More studies are urgently needed to understand how we can best target this system to reduce the growing burden of immune related diseases in the modern world."
Preeclampsia occurs in up to 10% of pregnancies and is characterised by high blood pressure, protein in the urine and severe swelling in the mother.
It is believed to develop due to a breakdown in maternal-fetal immune tolerance, as demonstrated by maternal immune alterations including reduced regulatory T (Treg) cells. Maternal immune changes in preeclampsia are generally mirrored in the fetal immune system. In turn, there is some evidence that preeclampsia is associated with higher rates of allergy, and cardiovascular disease in offspring.
Short chain fatty acids (SCFAs), mainly acetate, butyrate and propionate, are major metabolic products of the gut microbiota, mostly produced through bacterial fermentation of dietary fiber. SCFAs have potent anti-inflammatory effects, thought to relate to their role in the gut and systemic immune homeostasis.
Recent mice studies also showed that dietary acetate and butyrate can protect against the development of food allergy, asthma, and autoimmune type 1 diabetes (T1D) through modulation of immune tolerance (Marques. F.Z., et al 2017 and 2018).
there is some evidence suggesting maternal gut microbiota may influence the pathogenesis of preeclampsia, with probiotic use associated with a reduced risk of preeclampsia (Brantsaeter, A. L. et al. 2011).
Source: Nature Communications
Hu. M., et al
"Decreased maternal serum acetate and impaired fetal thymic and regulatory T cell development in preeclampsia"