Effects of Maternal Gut Microbiota-Targeted Therapy on the Programming of Nonalcoholic Fatty Liver Disease in Dams and Fetuses, Related to a Prenatal High-Fat Diet

Abstract

Metabolic disorders can start in utero. Maternal transmission of metabolic phenotypes may increase the risks of adverse metabolic outcomes, such as nonalcoholic fatty liver disease (NAFLD); effective intervention is essential to prevent this. The gut microbiome plays a crucial role in fat storage, energy metabolism, and NAFLD. We investigated the therapeutic use of probiotic Lactobacillus reuteri and postbiotic butyrate gestation in the prevention of perinatal high-fat diet-induced programmed hepatic steatosis in the offspring of pregnant Sprague–Dawley rats who received regular chow or a high-fat (HF) diet 8 weeks before mating. L. reuteri or sodium butyrate was administered via oral gavage to the gestated rats until their sacrifice on day 21 of gestation. Both treatments improved liver steatosis in pregnant dams; L. reuteri had a superior effect. L. reuteri ameliorated obesity and altered the metabolic profiles of obese gravid dams. Maternal L. reuteri therapy prevented maternal HF diet-induced fetal liver steatosis, and reformed placental remodeling and oxidative injury. Probiotic therapy can restore lipid dysmetabolism in the fetal liver, modulate nutrient-sensing molecules in the placenta, and mediate the short-chain fatty acid signaling cascade. The therapeutic effects of maternal L. reuteri on maternal NAFLD and NAFLD reprogramming in offspring should be validated for further clinical translation.

Heat-Killed Lacticaseibacillus paracasei Repairs Lipopolysaccharide-Induced Intestinal Epithelial Barrier Damage via MLCK/MLC Pathway Activation

“…Recently, postbiotics have increasingly been seen as microorganisms and/or their parts that help the host’s health, having beneficial biological activities for the prevention of metabolic diseases [ 39 ]. Experimental studies show that postbiotics alleviated the effects of metabolic diseases [ 40 ]. Therefore, we screened and examined the effects of heat-killed L. paracasei strains with different cultivation times on the function of the intestinal barrier and explored the expression of tight proteins and inflammatory factors by shielding the monolayer of Caco-2 cells against LPS-induced Caco-2 cell monolayers.…”

The dogma of the sterile uterus revisited: does microbial seeding occur during fetal life in humans and animals?

“…Although an initial seeding might happen in utero , this is easily overcome by the strong colonization during and after birth. The prenatal environment is responsible for a long-term imprinting of the immune system, and the so-called programming might be related to the maternal gut microbiome ( Gomez de Agüero et al 2016 , Gao & Sun 2021 , Yu et al 2022 ). However, this is rather associated with specific bacterial components than with living microorganisms ( Luoto et al 2010 , Rautava et al 2012 , Thum et al 2012 , Brosseau et al 2021 ).…”

Impact of Gut–Brain Axis on Hepatobiliary Diseases in Fetal Programming

“…The impact of probiotic Lactobacillus reuteri and sodium butyrate was tested on pregnant mice and was found to reduce fat in the liver and improved liver steatosis in the mother and in the offspring. The authors believed that Lactobacillus reuteri could be used as an adjuvant therapy in the treatment of NAFLD in pregnant women and as a de-programming strategy for NAFLD in the offspring of NAFLD patients [84]. Administration of the prebiotic oligofructose to pregnant mice with NAFLD also improved hepatic steatosis in both male and female offspring and lowered the probability of developing a more severe steatosis or NAFLD in offspring [85].…”