Lachnospiraceae -derived butyrate mediates protection of high fermentable fiber against placental inflammation in gestational diabetes mellitus

Abstract

Inflammation-associated insulin resistance is a key trigger of gestational diabetes mellitus (GDM), but the underlying mechanisms and effective interventions remain unclear. Here, we report the association of placental inflammation (tumor necrosis factor–α) and abnormal maternal glucose metabolism in patients with GDM, and a high fermentable dietary fiber (HFDF; konjac ) could reduce GDM development through gut flora–short-chain fatty acid–placental inflammation axis in GDM mouse model. Mechanistically, HFDF increases abundances of Lachnospiraceae and butyrate, reduces placental-derived inflammation by enhancing gut barrier and inhibiting the transfer of bacterial-derived lipopolysaccharide, and ultimately resists high-fat diet–induced insulin resistance. Lachnospiraceae and butyrate have similar anti-GDM and anti–placental inflammation effects, and they can ameliorate placental function and pregnancy outcome effects probably by dampening placental immune dysfunction. These findings demonstrate the involvement of important placental inflammation–related mechanisms in the progression of GDM and the great potential of HFDFs to reduce susceptibility to GDM through gut-flora-placenta axis.

Effects of dietary fiber on maternal health in pregnant women with metabolic syndrome risk: a randomized controlled trial

“…37 Additionally, inflammation-driven insulin resistance was shown to play a crucial role in GDM, with high fermentable dietary fiber (HFDF) reducing GDM development in mice by modulating the gut flora–short-chain fatty acid–placental inflammation axis. 38 In line with these findings, our study also indicated that inadequate dietary fiber intake increased the risk of GDM. This correlation remained significant even after adjusting for maternal age and pre-pregnancy BMI in the control group.…”

Maternal or post-weaning dietary fructo-oligosaccharide supplementation reduces stillbirth rate of sows and diarrhea of weaned piglets

“…The placenta is a key bridge between mother and fetus and plays an important role in fetal development ( Hu et al., 2021 ). Reduced insulin sensitivity is associated with trophoblast invasion and angiogenesis impairment, resulting in reduction of reproductive efficiency, with further adverse effects on fetal outcomes, such as high stillbirth rates and low birth weight ( Huang et al., 2023 ; Martino et al., 2016 ; Tan et al., 2016 ; Tanaka et al., 2018 ; Yang et al., 2021b ). A richer vascular system could efficiently transport oxygen and nutrients from mother to fetus, thus increasing the vitality of piglets ( Huang et al., 2021a , b ).…”

Maternal gut microbiota in the health of mothers and offspring: from the perspective of immunology

“…Recently, Huang et al. found that high dietary fiber, which increased abundances of Lachnospiraceae and butyrate, enhanced the gut barrier and inhibited the transfer of LPS, thus reducing placental inflammation and insulin resistance ( 246 ). Similar results were also found in pigs.…”