Targeting the microbiota to address diet-induced obesity: a time dependent challenge.

Siobhan F Clarke,Fergus Shanahan,Paul W O'Toole,Paul D Cotter,Eileen F Murphy,R Paul Ross,Orla O'Sullivan,Stefan Bereswill

doi:10.1371/journal.pone.0065790

Abstract

Links between the gut microbiota and host metabolism have provided new perspectives on obesity. We previously showed that the link between the microbiota and fat deposition is age- and time-dependent subject to microbial adaptation to diet over time. We also demonstrated reduced weight gain in diet-induced obese (DIO) mice through manipulation of the gut microbiota with vancomycin or with the bacteriocin-producing probiotic Lactobacillus salivarius UCC118 (Bac+), with metabolic improvement achieved in DIO mice in receipt of vancomycin. However, two phases of weight gain were observed with effects most marked early in the intervention phase. Here, we compare the gut microbial populations at the early relative to the late stages of intervention using a high throughput sequencing-based analysis to understand the temporal relationship between the gut microbiota and obesity. This reveals several differences in microbiota composition over the intervening period. Vancomycin dramatically altered the gut microbiota composition, relative to controls, at the early stages of intervention after which time some recovery was evident. It was also revealed that Bac+ treatment initially resulted in the presence of significantly higher proportions of Peptococcaceae and significantly lower proportions of Rikenellaceae and Porphyromonadaceae relative to the gut microbiota of L. salivarius UCC118 bacteriocin negative (Bac-) administered controls. These differences were no longer evident at the later time. The results highlight the resilience of the gut microbiota and suggest that interventions may need to be monitored and continually adjusted to ensure sustained modification of the gut microbiota.

Highlights

Obesity is due to a surplus of energy intake over expenditure, resulting in storage of excess energy as fat
[6] we have previously investigated the impact of administering the glycopeptide antibiotic vancomycin and the bacteriocin-producing probiotic Lactobacillus salivarius UCC118 (Bac+) to diet-induced obese (DIO) mice
There is a significant reduction in weight gain in DIO mice at intervention weeks 2–4 in the Bac+ intervention, when compared to Bac- intervention, but this does not persist with time (Figure 1A)

Summary

Introduction

Obesity is due to a surplus of energy intake over expenditure, resulting in storage of excess energy as fat This is only part of a bigger story; an emerging theme is the relationship between the composition and functionality of microorganisms in the gut with obesity. We previously showed that compositional changes in the faecal microbiota associated with diet-induced obesity are timedependent and unrelated to markers of energy harvest, which change over time. Vancomycin resulted in an improvement in the metabolic abnormalities associated with obesity, including a significant reduction in weight gain, by the end of the intervention period. When compared with an isogenic non-bacteriocin producing control (Bac-), the L. salivarius UCC118 Bac+ strain alters the gut microbiota but did not significantly alter metabolic markers or weight gain as measured at the end of the intervention period. The results reflect the resilience of the gut microbiota and show that therapeutic manipulation of the microbiota is likely to be more complex than anticipated with sustained adjustment likely to require multiple interventions over time

Methods

Results

Conclusion