A structured weight loss program increases gut microbiota phylogenetic diversity and reduces levels of Collinsella in obese type 2 diabetics: A pilot study

Abstract

The global obesity epidemic constitutes a major cause of morbidity and mortality challenging public health care systems worldwide. Thus, a better understanding of its pathophysiology and the development of novel therapeutic options are urgently needed. Recently, alterations of the intestinal microbiome in the obese have been discussed as a promoting factor in the pathophysiology of obesity and as a contributing factor to related diseases such as type 2 diabetes and metabolic syndrome. The present pilot study investigated the effect of a structured weight loss program on fecal microbiota in obese type 2 diabetics. Twelve study subjects received a low-calorie formula diet for six weeks, followed by a nine week food reintroduction and stabilization period. Fecal microbiota were determined by 16S rRNA gene sequencing of stool samples at baseline, after six weeks and at the end of the study after fifteen weeks. All study subjects lost weight continuously throughout the program. Changes in fecal microbiota were most pronounced after six weeks of low-calorie formula diet, but reverted partially until the end of the study. However, the gut microbiota phylogenetic diversity increased persistently. The abundance of Collinsella, which has previously been associated with atherosclerosis, decreased significantly during the weight loss program. This study underlines the impact of dietary changes on the intestinal microbiome and further demonstrates the beneficial effects of weight loss on gut microbiota. Trial registration: ClinicalTrials.gov NCT02970838.

Conflict of interest statement

Nestlé Health Science Germany granted the study participants a 15% discount to the Optifast formula diet. LS received a Gerhard Domagk scholarship from University Medicine Greifswald made possible through an unrestricted educational grant from Baxter Deutschland GmbH (Unterschleissheim, Germany), Profusio GmbH (Greven, Germany) and Nutricia GmbH (Erlangen, Germany). This does not alter our adherence to all PLOS ONE policies on sharing data and materials.

Figures

Fig 1. CONSORT flow diagram.

Fig 2. Development of body mass index and alpha diversity indices over the study course.

Plots are portraying the changes of body mass index (BMI, left), Phylogenetic diversity (PD, middle) and Simpson diversity number (N2, right) at baseline/0 weeks, after six weeks of low-calorie formula diet and after regular food reintroduction at fifteen weeks. At each time point paired samples of 12 participants were evaluated. Samples corresponding to one individual are connected by a black line. + signs indicate the means. The decrease of BMI during the study was associated with an increase of PD. * indicates significant difference determined by Friedman test.

Fig 3. Principal coordinate analysis (PCoA) of Bray-Curtis dissimilarity.

PCoA of 36 gut microbiota samples belonging to twelve participants at three different time points (baseline/0 weeks, six weeks and fifteen weeks). The two major PCo1 and PCo2 are shown. All samples are connected to the centroid (displayed as square) of their respective time point. The microbial communities shifted markedly between baseline and six weeks, then returned towards baseline after fifteen weeks.

Fig 4. Taxon composition at baseline, 6 and 15 weeks after study launch.

Stacked bar plots portraying the average sample composition of the study group (n = 12) at baseline/0 weeks, after six weeks of low-calorie formula diet and after regular food reintroduction at fifteen weeks. Taxon abundance changes were most prominent at six weeks, but mostly not sustained at fifteen weeks.

Fig 5. Genera with significantly different abundance between different time points.

Plots are portraying the relative abundance changes of the study group (n = 12) including all significantly altered genera at baseline/0 weeks, after six weeks of low-calorie formula diet and after regular food reintroduction at fifteen weeks. Samples corresponding to one individual are connected by a black line. At the end of the study, only abundance changes of Collinsella were sustained. inc. sed.: incertae sedis.