Synbiotic use is associated with shifts in the gut microbiome but not protection from high-fat diet associated Dysbiosis in juvenile non-human primates. gut metagenome

Background: Dysbiosis of the gut microbiome has been associated with both obesity and diet. Our group and others have previously shown that the mammalian gut microbiome is largely influenced by diet. Specifically, we have demonstrated in our non-human primate model that a high-fat maternal diet is associated with alterations in the offspring gut microbiome at one year of age. Here, we aimed to further these studies by examining alterations in the juvenile gut microbiome associated with synbiotic supplementation following maternal high-fat diet exposure. Furthermore, we examined whether synbiotic supplementation buffers against gut dysbiosis induced by a postnatal high-fat diet challenge.Methods: Japanese macaque (Macaca fuscata) juveniles were exposed to a high-fat diet during gestation and lactation and weaned onto a control diet. Around 18 months of age, juveniles were supplemented with a synbiotic comprised of a synbiotic containing psyllium seed and Enterococcus faecium, Lactobacillus acidophilus, L. casei, and L. plantarum, over three months. Serum samples for lipid analysis were taken at pre-supplementation and one-month post-supplementation. Anal swabs and stool were collected at pre-supplementation, mid-supplementation, post-supplementation, and during a post-supplementation high-fat diet challenge. DNA was isolated and 16S-based sequencing of microbial DNA was performed.Results: Overall, we found that juveniles receiving synbiotics had a minimally altered gut microbiome. Specifically, after 3 months of symbiotic supplementation, juveniles demonstrated decreased abundances of several bacterial genera, including Faecalibacterium and Anaerovibrio. Examination of inferred bacterial metabolic pathways revealed a decrease in fatty acid metabolism, alongside alterations in pathways previously associated with protection from colitis. Serum lipid analysis revealed significant decreases in maternal high-fat diet-induced juvenile elevated triglycerides, cholesterol, and LDL, but no change in HDL, in association with supplementation. Despite these changes, juveniles challenged with a post-supplementation high-fat diet challenge failed to demonstrate subsequent protection from dysbiosis of the gut microbiome, although prior synbiotic supplementation was associated with alterations in carbohydrate metabolism.Conclusions: The use of synbiotics is associated with minimal alterations of the gut microbiome in offspring exposed to a maternal high-fat diet, then weaned onto a control diet. Furthermore, prior use of synbiotics does not protect against gut dysbiosis during subsequent high-fat diet challenge.