Schellekens_BLongum_Obesity_Stress_EBIOM_103176 (003)

EBioMedicine xxx (xxxx) 103176

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Research paper Bifidobacterium longum counters the effects of obesity: Partial successful translation from rodent to human Harriët Schellekens a , b , # , £ , ⁎ , Cristina Torres-Fuentes a , # , Marcel van de Wouw a , # , Caitriona M. Long-Smith a , Avery Mitchell c , Conall Strain c , Kirsten Berding a , Thomaz F.S. Bastiaanssen a , b , Kieran Rea a , Anna V. Golubeva a , b , Silvia Arboleya a , c , Mathieu Verpaalen a , b , Matteo M. Pusceddu a , Amy Murphy a , c , Fiona Fouhy a , c , Kiera Murphy a , c , Paul Ross a , d , Bernard L. Roy e , Catherine Stanton a , c ,

Timothy G. Dinan a , f , John F. Cryan a , b , £ a APC Microbiome Ireland, University College Cork, Cork, Ireland b Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland c Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland d College of Science Engineering & Food Science, University College Cork, Cork, Ireland e Cremo SA, Villars-sur-Glâne, Fribourg, Switzerland f Dept of Psychiatry and Behavioural Neuroscience, University College Cork, Cork, Ireland

ARTICLE INFO Article history: Received 6 May 2020 Received in revised form 13 October 2020 Accepted 3 December 2020 Available online xxx

ABSTRACT Background: The human gut microbiota has emerged as a key factor in the development of obesity. Certain pro- biotic strains have shown anti-obesity effects. The objective of this study was to investigate whether Bifidobac- terium longum APC1472 has anti-obesity effects in high-fat diet (HFD)-induced obese mice and whether B. longum APC1472 supplementation reduces body-mass index (BMI) in healthy overweight/obese individuals as the pri- mary outcome. B. longum APC1472 effects on waist-to-hip ratio (W/H ratio) and on obesity-associated plasma biomarkers were analysed as secondary outcomes. Methods: B. longum APC1472 was administered to HFD-fed C57BL/6 mice in drinking water for 16 weeks. In the human intervention trial, participants received B. longum APC1472 or placebo supplementation for 12 weeks, during which primary and secondary outcomes were measured at the beginning and end of the intervention. Findings: B. longum APC1472 supplementation was associated with decreased bodyweight, fat depots accumula- tion and increased glucose tolerance in HFD-fed mice. While, in healthy overweight/obese adults, the supplemen- tation of B. longum APC1472 strain did not change primary outcomes of BMI (0.03, 95% CI [-0.4, 0.3]) or W/ H ratio (0.003, 95% CI [-0.01, 0.01]), a positive effect on the secondary outcome of fasting blood glucose levels was found (-0.299, 95% CI [-0.44, -0.09]). Interpretation: This study shows a positive translational effect of B. longum APC1472 on fasting blood glucose from a preclinical mouse model of obesity to a human intervention study in otherwise healthy overweight and obese individuals. This highlights the promising potential of B. longum APC1472 to be developed as a valuable supple- ment in reducing specific markers of obesity. Funding: This research was funded in part by Science Foundation Ireland in the form of a Research Centre grant (SFI/12/RC/2273) to APC Microbiome Ireland and by a research grant from Cremo S.A. ©2020

Keywords Obesity Translational Fasting blood glucose Ghrelin Cortisol Gut microbiota Probiotic Bifidobacterium longum

For submission to EBioMedicine

⁎ Corresponding author. E-mail address: (H. Schellekens) # Equal contributing authors £ joint senior authors 2352-3964/© 2020.

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