Microbiome of prebiotic-treated mice reveals novel targets involved in host response during obesity

Abstract

The gut microbiota is involved in metabolic and immune disorders associated with obesity and type 2 diabetes. We previously demonstrated that prebiotic treatment may significantly improve host health by modulating bacterial species related to the improvement of gut endocrine, barrier and immune functions. An analysis of the gut metagenome is needed to determine which bacterial functions and taxa are responsible for beneficial microbiota–host interactions upon nutritional intervention. We subjected mice to prebiotic (Pre) treatment under physiological (control diet: CT) and pathological conditions (high-fat diet: HFD) for 8 weeks and investigated the production of intestinal antimicrobial peptides and the gut microbiome. HFD feeding significantly decreased the expression of regenerating islet-derived 3-gamma (Reg3g) and phospholipase A2 group-II (PLA2g2) in the jejunum. Prebiotic treatment increased Reg3g expression (by ∼50-fold) and improved intestinal homeostasis as suggested by the increase in the expression of intectin, a key protein involved in intestinal epithelial cell turnover. Deep metagenomic sequencing analysis revealed that HFD and prebiotic treatment significantly affected the gut microbiome at different taxonomic levels. Functional analyses based on the occurrence of clusters of orthologous groups (COGs) of proteins also revealed distinct profiles for the HFD, Pre, HFD-Pre and CT groups. Finally, the gut microbiota modulations induced by prebiotics counteracted HFD-induced inflammation and related metabolic disorders. Thus, we identified novel putative taxa and metabolic functions that may contribute to the development of or protection against the metabolic alterations observed during HFD feeding and HFD-Pre feeding.

In Vivo Selection To Identify Bacterial Strains with Enhanced Ecological Performance in Synbiotic Applications

“…These findings provide a proof of concept for the potential of in vivo selection to identify synbiotic combinations that are, in ecological terms, highly synergistic. In addition to enhancing the abundance of strain IVS-1, the synbiotic used here also redressed the high-fatdiet-induced reduction in the level of bifidobacteria detected in rats that is often reported in the literature (41)(42)(43). Therefore, although no metabolic benefits were seen in the rat model used in our study, the synbiotic may be beneficial in other scenarios, as bifidobacteria are considered health-promoting organisms (6,26,(66)(67)(68).…”

“…2A). Decreases in numbers of bifidobacteria are often observed during high-fat-diet feeding (41)(42)(43). To determine if our synbiotic strategy could redress this decrease, we employed a rat model of highfat-diet-induced NAFLD where rats develop steatosis (fatty liver) but do not show an increase in body weight, develop liver inflammation, or progress to nonalcoholic steatohepatitis (NASH) (28).…”

Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics

“…Studies in mice have shown that oligofructose (a fruc tan) reduced diet induced obesity, diabetes, hepatic steato sis and inflammation by mechanisms linked with changes in specific gut microorganisms and meta genomics functions of bacteria 72 . A study in rats suggested that oligo fructose consumption might normalize the metabolomic signature of insulin resistance in obese rats and reduce obesity in offspring 73 .…”

Investigating cholesterol metabolism and ageing using a systems biology approach

“…For instance, a 5 d animal-based-diet significantly altered the abundance of twenty-two clusters, elevated faecal bile acid concentration, and increased BSH expression (99) . Everard et al (100) describe that high-fat feeding significantly affected twenty genera. This may have been influenced by a decline in the antimicrobial peptide regenerating islet-derived protein three gamma.…”