Objective The gut microbiota has been implicated in the aetiology of obesity and associated comorbidities. Patients with Prader-Willi syndrome (PWS) are obese but partly protected against insulin resistance. We hypothesised that the gut microbiota of PWS patients differs from that of non-genetically obese controls and correlate to metabolic health. Therefore, here we used PWS as a model to study the role of gut microbiota in the prevention of metabolic complications linked to obesity.
Design We conducted a case-control study with 17 adult PWS patients and 17 obese subjects matched for body fat mass index, gender and age. The subjects were metabolically characterised and faecal microbiota was profiled by 16S ribosomal RNA gene sequencing. The patients’ parents were used as a non-obese control group. Stool samples from two PWS patients and two obese controls were used for faecal microbiota transplantations in germ-free mice to examine the impact of the microbiota on glucose metabolism.
Results The composition of the faecal microbiota in patients with PWS differed from that of obese controls, and was characterised by higher phylogenetic diversity and increased abundance of several taxa such as Akkermansia, Desulfovibrio and Archaea, and decreased abundance of Dorea. Microbial taxa prevalent in the PWS microbiota were associated with markers of insulin sensitivity. Improved insulin resistance of PWS was partly transmitted by faecal microbiota transplantations into germ-free mice.
Conclusion The gut microbiota of PWS patients is similar to that of their non-obese parents and might play a role for the protection of PWS patients from metabolic complications.
- intestinal bacteria
- diabetes mellitus
- glucose metabolism
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Contributors KC, RC, FB, VT and CP designed and directed the project; RC, CP, MC, LO, JAW, LH, CA, AM, MK, RJ, AH, HG and VL performed the experiments; LO, VT and RC analysed data; RC, LO, VT, KC and CP wrote the article with inputs from FB and MC.
Funding This study was supported by several sources: European Union, FP7 Health (METACARDIS) (HEALTH-F4-2012-30531), Svenska Forskningsrådet Formas (2017-01996_3 and 2017-02001), Foundation Leducq (17CVD01), Agence Nationale de la Recherche (ANR-11-DPBS-0001 and ANR-10-IAHU-05), the Swedish Research Council (Vetenskapsrådet) and grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALFGBG- 718101). FB is Torsten Söderberg Professor in Medicine and recipient of an ERC Consolidator Grant (European Research Council, Consolidator grant 615362-METABASE).
Competing interests FB is in the Scientific Advisory Board of MetaboGen, Sweden.
Patient consent for publication Not required.
Ethics approval All animal procedures were approved by the Gothenburg Animal Ethics Committee (152–2015).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement 16S data are available at European Nucleotide Archive (accession number: PRJEB33908; http://www.ebi.ac.uk/ena/data/view/PRJEB33908)
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