Abstract

The past two decades of research have raised gut microbiota composition as a contributing factor to the development of obesity, and higher abundance of certain bacterial species has been linked to the lean phenotype, such as Akkermansia muciniphila. The ability of pre- and probiotics to affect metabolic health could be via microbial community alterations and subsequently changes in metabolite profiles, modulating for example host energy balance via complex signaling pathways. The aim of this mice study was to determine how administration of a prebiotic fiber, polydextrose (PDX) and a probiotic Bifidobacterium animalis ssp. lactis 420 (B420), during high fat diet (HFD; 60 kcal% fat) affects microbiota composition in the gastrointestinal tract and adipose tissue, and metabolite levels in gut and liver. In this study C57Bl/6J mice (N = 200) were split in five treatments and daily gavaged: 1) Normal control (NC); 2) HFD; 3) HFD + PDX; 4) HFD + B420 or 5) HFD + PDX + B420 (HFD+S). At six weeks of treatment intraperitoneal glucose-tolerance test (IPGTT) was performed, and feces were collected at weeks 0, 3, 6 and 9. At end of the intervention, ileum and colon mucosa, adipose tissue and liver samples were collected. The microbiota composition in fecal, ileum, colon and adipose tissue was analyzed using 16S rDNA sequencing, fecal and liver metabolomics were performed by nuclear magnetic resonance (NMR) spectroscopy. It was found that HFD+PDX intervention reduced body weight gain and hepatic fat compared to HFD. Sequencing the mice adipose tissue (MAT) identified Akkermansia and its prevalence was increased in HFD+S group. Furthermore, by the inclusion of PDX, fecal, lleum and colon levels of Akkermansia were increased and liver health was improved as the detoxification capacity and levels of methyl-donors were increased. These new results demonstrate how PDX and B420 can affect the interactions between gut, liver and adipose tissue.

Highlights

  • Despite an increased awareness of obesity having a negative impact on human health, according to OECD almost one out of four adults in OECD countries (24%) is obese [1]

  • The mechanism of probiotic, prebiotic and synbiotic treatment on fat accumulation was studied by administering high fat diet (HFD) to C57BL/6J mouse model susceptible to diet induced obesity

  • HFD resulted in drastic weight gain in C57BL/6J mice and induced a dramatic shift in gut microbiota composition by increasing Firmicutes and decreasing Bacteroidetes in phylum level–this diet-induced reshape of the composition in microbial community under HFD is well-characterized and in accordance with previous literature [41]

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Summary

Introduction

Despite an increased awareness of obesity having a negative impact on human health, according to OECD almost one out of four adults in OECD countries (24%) is obese [1]. As reviewed by Kobyliak and coworkers [6], intervention studies in both animals and humans demonstrate that the intake of probiotics can assist in reducing body weight gain in animals on a high energy diet and ameliorate metabolic health risk factors such as insulin resistance in humans. Lactis 420 (B420) has shown potential as weight controlling agent, since administrating it has resulted in a reduction of body fat mass accumulation in mice fed the high fat diet (HFD) [7, 8]. A synergistic effect between B420 and a prebiotic soluble fiber, polydextrose (PDX) [9, 10], has been indicated by our group, when a lower accumulation of body fat mass with the combination of these two ingredients was noted in humans during a 6-month intervention period in a randomized double-blind clinical trial [11]. PDX has shown potential in supporting metabolic health and weight management, as reported in several preclinical and clinical studies [15,16,17,18]

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