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

TLDR

The gut microbiota is implicated in metabolic and immune disorders linked to obesity and type 2 diabetes. The study aimed to analyze the gut metagenome to identify bacterial functions and taxa responsible for beneficial microbiota–host interactions following nutritional intervention. Mice were treated with a prebiotic under control and high‑fat diet conditions for eight weeks, and the production of intestinal antimicrobial peptides and the gut microbiome were examined. Prebiotic treatment markedly increased Reg3g expression, restored intestinal homeostasis, and, based on deep metagenomic sequencing, altered gut microbiota composition and function to counteract high‑fat‑diet‑induced inflammation and metabolic disorders, revealing novel taxa and metabolic pathways that may influence obesity‑related outcomes.

Abstract

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.