Role of modified diet and gut microbiota in metabolic endotoxemia in mice.

ABSTRACT

This study was aimed at investigating the effect of cultured gut microbiota (GM) from obese humans coupled HFD in inducing metabolic endotoxemia in humanized mice. In total, 30 strains were isolated from 10 stool samples of obese patients. Following morphological and biochemical characterization, 16S rRNA gene sequencing of six abundant isolates identified these Klebsiella aerogenes, Levilactobacillus brevis, Escherichia coli, Staphylococcus aureus, Bacillus cereus and Bacillus subtilis (MZ052089-MZ052094). In vivo trial using above isolates, known as human gut microbiota (HGM), was performed for six months. Sixteen mice were distributed into four groups, i.e., G1 (control) mice fed with chow diet, group 2 (G2) with HFD, group 3 (G3) with HFD + HGM and group 4 (G4) with chow diet + HGM. Body mass index (BMI) and plasma endotoxins were measured pre- and post-experiment. In vivo study revealed that HFD + HGM caused significant increase (3.9 g/cm at 20 weeks) in the body weight and BMI (0.4 g/cm post-experiment) of G3 mice compared to the other groups. One-way ANOVA showed significantly higher level of endotoxins (2.41, 4.08 and 3.7 mmol/L) in mice groups G2, G3 and G4, respectively, indicating onset of metabolic endotoxemia. Cecal contents of experimental mice groups showed a shift in microbial diversity as observed by all isolates belonging to either Firmicutes or Bacteroidetes phyla, respectively. In conclusion, current study reported that minor alteration in GM composition through HFD feeding and cultured GM transfer has significant impact in development of metabolic endotoxemia, possibly via modified intestinal permeability.