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expression in HFD-fed mice ( p = 0.001). While a reduced expression was observed for the anorexigenic pro-opiomelanocortin ( POMC ) gene expression in HFD-fed animals treated with B. longum APC1472 com- pared to HFD-fed, this did not reach statistical significance. Finally, no significant change in leptin ( LEP-R ) nor ghrelin ( GHS-R1a ) receptor ex- pression was observed ( Figure S3 ). 5.4. Human intervention study population In the human study, no significant differences were observed in weight, BMI, W/H ratio, age, height, sex, ethnicity, mode of delivery, alcohol consumption, and medical/surgical history at baseline between B. longum APC1472 treatment and placebo groups, as well as compli- ance ( Table 1 ). We did observe an increased prevalence of concomi- tant medical or nutritional supplement consumption in the treatment group (48.6%) compared to the placebo group (33.3%). In addition, we also observed differences in the socioeconomic profile where there was a lower prevalence of employers and managers in the treatment group (2/74) compared to the placebo group (4/48). Similarly, we observed a lower prevalence of past smokers in the treatment group (28/74) com- pared to the placebo group (9/48). In conclusion, the baseline charac- teristics of our placebo group and B. longum APC1472 group are mostly the same.
Physical activity and food intake patterns were also assessed throughout the study using self-report questionnaires ( Table S2, S3 ). No differences in physical activity levels or calorie, macro- and micronutri- ent intake were observed over the 12-week treatment period or between the placebo and B. longum APC1472 group. 5.5. Adverse events There were seven adverse events (6 placebo participants and 1 treat- ment participant) that were possibly related to the investigational prod- uct. The adverse event of the treatment participant was constipation. The remaining 6 adverse events for placebo participants were; gastroin- testinal discomfort and increased appetite; bloating; increased flatu- lence; aches in joints and increased temperature; rash on knees, elbows, scalp and red blotches on chest & upper arm. 5.6. B. longum APC1472 does not affect BMI and W/H ratio in humans The primary outcome of this study was to investigate whether B. longum APC1472 supplementation could alter BMI, and a secondary out- come of change in W/H ratio was included to support the primary outcome. However, no differences were observed in BMI and W/H ra- tio over the 12-week treatment period, or between the placebo and B. longum APC1472 treatment groups ( Fig. 4 ). 5.7. B. longum APC1472 improves fasting glucose levels independent of other blood markers of energy metabolism and satiety in humans We subsequently measured markers associated with host energy me- tabolism and satiety as part of the secondary and exploratory outcome measures ( Fig. 5 and Table S4 for full statistical results). Here we ob- served that both the B. longum APC1472 and the placebo arm reduced fasting glucose levels over the 12-week treatment period ( Fig. 5A ). However, glucose levels were 0.266 mmol/L (95% CI [ − 0.44, − 0.09]) lower in the B. longum APC1472 group compared with the placebo group ( F (1112) = 9.073, p =0.003; q =0.075) ( Fig. 5B ). The effect size of the B. longum APC1472-induced decrease was moderate ( η 2 =0.075). We also observed that HbA1c levels decreased over the 12-week treat- ment period in both the placebo group ( t (62.372) = 4.277, p <0.001) and B. longum APC1472 treatment group ( t (85.983) = 5.787, p < 0.001) ( Fig. 5C ). However, there were no differences between the groups, indicating that the decrease in HbA1c levels is most likely ex- plained by the 12-week treatment period or placebo effect. No changes were observed in other biomarkers of host energy metabolism such as insulin, C-peptide, ghrelin (active and total), GLP-1 (active and total), PYY and leptin levels ( Fig. 5E-T ). 5.8. B. longum APC1472 does not influence human lipid and inflammatory profiles in humans It is well-known that obesity is associated with metabolic syndrome, hypertension and hyperlipidaemia [63]. B. longum APC1472 did not im- pact lipid profiles (i.e. cholesterol, triglycerides and LDL), and inflam- matory profiles (i.e. IL-10, TNF- α and IFN γ ) compared to the placebo group ( Table 2 ). In addition, vital signs remained unaltered through- out the study ( Table S5 ). These results reveal that B. longum APC1472 did not evoke any negative effects on vital signs or induced any in- flammation. Interestingly, even though no significant changes were ob- served in HDL levels over the 12-week treatment period, a small in- crease in HDL levels was observed in the B. longum APC1472 group ( F (1117) = 3.260, p = 0.074). The effect-size of the increase in HDL levels was small ( η 2 =0.027).
Table 1 Baseline characteristics of subjects in the placebo and treatment arms at visit 1 (screening visit).
Placebo ( n = 48, mean ± STD)
B. longum APC1472 ( n =74, mean± STD)
Variable
Weight (kg) W/H ratio Age (years) Height (m) BMI
87.9±1.7 31.2±0.3 0.95±0.01 46.3±9.9 1.67±0.10 19 (39.6%) 29 (60.4%) 48 (100%) 0 (0%) 15 (31.3%) 14 (29.2%) 4 (8.3%) 4 (8.3%) 4 (8.3%) 3 (6.3%)
89.0±1.3 30.8±0.2 0.96±0.01 44.9±11.4 1.70±0.09 34 (45.9%) 40 (54.1%) 73 (98.6%) 1 (1.4%) 21 (28.4%) 19 (25.7%) 8 (10.8%) 8 (10.8%) 2 (2.7%) 7 (9.5%) 5 (6.8%) 2 (2.7%)
Sex (no. of subject (%)) Male
Female
Race or ethnicity (no. of subject (%)) Caucasian
Arabic
Socioeconomic status (no. of subject (%)) Non-manual
Lower Professional Manual skilled Semi-skilled Employers and managers Own account workers Higher Professional
3 (6.3%) 1 (2.1%)
All others gainfully occupied and unknown
Farmer Unskilled
0 (0%) 0 (0%)
1 (1.4%) 1 (1.4%)
Smoking status (no. of subject (%)) Non-smoker
22 (45.8%) 17 (35.4%) 9 (18.8%)
40 (54.1%) 28 (37.8%) 6 (8.1%)
Past smoker Current smoker
Alcohol consumption (mean ± SEM) Units per week
4.97±0.68 4.31±0.46 Currently on concomitant medical or nutritional supplements (no. of subject (%)) Yes 16 (33.3%) 36 (48.6%) No 32 (66.7%) 38 (51.4%) Compliance (% product consumed) Week 6 95.8±1.2 97.9±0.8 Week 12 94.0±2.0 97.2±1.2 Abbreviations: BMI = Body-mass index; W/H ratio = waist-to-hip ratio.
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