Schellekens_BLongum_Obesity_Stress_EBIOM_103176 (003)


H. Schellekens et al. / EBioMedicine xxx (xxxx) 103176

Fig. 5. B. longum APC1472 supplementation reduces fasting blood glucose levels in overweight and obese individuals. Markers associated with host metabolism and satiety were measured as the beginning of the study (pre), after 6 weeks (mid) and after 12 weeks (post) of treatment. All data are depicted of all 3 timepoints (A, C, E, G, I, K, M, O, Q, R), as well as the change after 12 weeks compared to at the beginning of the study (B, D, F, H, J, L, N, P, R, T). Data are depicted as boxplot or scatter dot plot, where the dots depict individual datapoints, with n = 48 for the placebo group and n =74 for the B. longum APC1472 treatment group. * indicates a significant effect (* p <0.05, ** p <0.01, *** p <0.001). tially ameliorated the HFD-induced decrease in Bifidobacteriaceae rela- tive abundance ( p = 0.054, adjusted p =0.170) ( Figure S5D ).

6. Discussion There has been an increased emphasis on gut microbiota-targeted therapeutics for the amelioration of obesity [4,11,68,[69,101]]. For ex- ample, recent studies have identified several probiotic strains with dif- ferent anti-obesity effects, including members of the genus Bifidobac- terium [4,30-36], but the exact mechanisms of action are still lacking. In the present study, we demonstrate that a novel isolated B. longum APC1472 strain, which was previously shown to attenuate ghrelinergic signalling [37], reduces body weight gain, fat depot size, glucose tol- erance and leptin levels in a preclinical mouse model of HFD-induced obesity. Furthermore, when the B. longum APC1472 strain was inves- tigated in a human cohort of healthy overweight and obese individu- als, a reduced fasting blood glucose level was observed. Noteworthy, stratification and analysis of the obese human subpopulation revealed that B. longum APC1472 was able to normalize active ghrelin levels and the cortisol awakening response, which are both dysregulated in obe- sity [44,70-74]. This highlights the translational value of this novel Bifidobacterium longum species, B. longum APC1472, from a preclinical mouse model to a human intervention study where this probiotic posi

Analysis of the faecal microbiota in the human intervention study revealed that B. longum APC1472 did not impact the alpha diversity indices (Shannon, Simpson and Chao1 , Fig. 7A-C ). Furthermore, the overall composition of the microbiota remained unaffected as deter- mined by the PCA analysis of the beta diversity ( Fig. 7D ). B. longum APC1472 did increase Bifidobacterium relative abundance over the 12-week intervention period (t(57) = − 2.891, p = 0.005), which was not observed in the placebo group ( Fig. 7E ). This resulted in a higher Bifidobacterium abundance in the treatment group compared to the placebo group post-intervention (F(3, 89) = 5.922, p =0.017) ( Fig. 7F ). Similar results were observed in the obese subpopulation ( Figure S6 ). Short-chain fatty acids (SCFAs) are potentially one of the most in- vestigated gut microbiota-derived metabolites implicated in host energy metabolism and obesity symptomatology [10,67]. Analysis of faecal SCFA levels in human samples revealed no differences in levels of ac- etate, propionate, butyrate and valerate ( TableS6 ). Furthermore, isobu- tyrate and isovalerate levels remained unaffected ( Table S6 ).

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