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Original research
Discovery of the gut microbial signature driving the efficacy of prebiotic intervention in obese patients
  1. Julie Rodriguez1,
  2. Sophie Hiel1,
  3. Audrey M Neyrinck1,
  4. Tiphaine Le Roy1,2,
  5. Sarah A Pötgens1,
  6. Quentin Leyrolle1,
  7. Barbara D Pachikian1,
  8. Marco A Gianfrancesco3,
  9. Patrice D Cani1,2,
  10. Nicolas Paquot3,
  11. Miriam Cnop4,5,
  12. Nicolas Lanthier6,
  13. Jean-Paul Thissen7,
  14. Laure B Bindels1,
  15. Nathalie M Delzenne1
  1. 1Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium
  2. 2WELBIO- Walloon Excellence in Life Sciences and BIOtechnology, UCLouvain, Université catholique de Louvain, Brussels, Belgium
  3. 3Laboratory of Diabetology, Nutrition and Metabolic disease, Université de Liège, Liège, Belgium
  4. 4ULB Center for Diabetes Research, Université Libre de Bruxelles, Brussels, Belgium
  5. 5Division of Endocrinology, Erasmus Hospital, Université Libre de Bruxelles, Brussels, Belgium
  6. 6Service d'Hépato-Gastroentérologie, Cliniques Universitaires Saint-Luc, Brussels, Belgium
  7. 7Departement of Diabetology and Nutrition, Institut de recherche expérimentale et clinique, Université catholique de Louvain, Brussels, Belgium
  1. Correspondence to Professor Nathalie M Delzenne, Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium; nathalie.delzenne{at}uclouvain.be

Abstract

Objective The gut microbiota has been proposed as an interesting therapeutic target for metabolic disorders. Inulin as a prebiotic has been shown to lessen obesity and related diseases. The aim of the current study was to investigate whether preintervention gut microbiota characteristics determine the physiological response to inulin.

Design The stools from four obese donors differing by microbial diversity and composition were sampled before the dietary intervention and inoculated to antibiotic-pretreated mice (hum-ob mice; humanised obese mice). Hum-ob mice were fed with a high-fat diet and treated with inulin. Metabolic and microbiota changes on inulin treatment in hum-ob mice were compared with those obtained in a cohort of obese individuals supplemented with inulin for 3 months.

Results We show that hum-ob mice colonised with the faecal microbiota from different obese individuals differentially respond to inulin supplementation on a high-fat diet. Among several bacterial genera, Barnesiella, Bilophila, Butyricimonas, Victivallis, Clostridium XIVa, Akkermansia, Raoultella and Blautia correlated with the observed metabolic outcomes (decrease in adiposity and hepatic steatosis) in hum-ob mice. In addition, in obese individuals, the preintervention levels of Anaerostipes, Akkermansia and Butyricicoccus drive the decrease of body mass index in response to inulin.

Conclusion These findings support that characterising the gut microbiota prior to nutritional intervention with prebiotics is important to increase the positive outcome in the context of obesity and metabolic disorders.

  • gut microbiota
  • inulin
  • faecal material transfer
  • obesity
  • metabolism
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Footnotes

  • Twitter @JulieRdz1213, @Titicaccae, @MicrObesity, @Laure_Bindels

  • Contributors JR and NMD conceived and designed the experiments, interpreted the data and wrote the manuscript. JR performed the experiments and data analysis. AMN and LBB participated to design and to experiments. TLR designed the FMT protocol. JR, SH, BDP, MAG, MC, NP, NL and J-PT participated to the acquisition of the clinical data. AMN, TLR, SAP, QL and LBB participated to the analysis and interpretation of data. AMN, PDC, MC, NP, NL, J-PT and LBB provided intellectual input on the paper and reviewed the paper. NMD supervised the overall project.

  • Funding This research is supported by the competitive cluster Wagralim from Wallonia (FOOD4GUT 518 project, convention 1318148). NMD is a recipient of grants from Wallonia (FOOD4GUT project; 519 FiberTAG project from European Joint Programming Initiative 'A Healthy Diet for a Healthy 520 Life') and from Belgium National Scientific Research Fund (FRS-FNRS; convention PDR 521 T.0068.19). PDC is a senior research associate at FRS-FNRS (Fonds de la Recherche 522 Scientifique), Belgium, and supported by the Funds Baillet Latour (Grant for Medical Research 523 2015). TLR is a postdoc fellow funded by FRFS-WELBIO (WELBIO-CR-2017C-02).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval Trial registered at ClinicalTrial.gov as NCT03852069 was approved by the 'Comité d’éthique Hospitalo-facultaire de Saint-Luc'.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement For the gut microbiota analysis, raw sequences can be accessed in Sequence Read Archive database (SRA accession numbers PRJNA594535, PRJNA595949).

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