4. Discussion
NAFLD, traits of metabolic syndrome, hyperphagia, liver steatosis, inflammation, constipation, overweight
METABOLIC SYNDROME, INFLAMMATION, LIVER STEATOSIS
At baseline, the FAS population was characterized by abdominal overweight (inclusion criterion). The traits related to this feature were in line with this, such as the mean values of BMI, waist circumference, WHtR, blood pressure, BFM, VATThe three groups did not significantly differ in baseline characteristics and laboratory findings, with the exception of HDL-C and ALT. With 2 out of 24 parameters, this is close to what one might expect as accidental significance. Accidental difference is also indicated by the lack of differences in parameters that are associated with HDL-C as part of metabolic syndrome, such as weight, BMI, waist circumference, WHtR, blood pressure, plasma glucose and HOMA-IR [Out of 180 randomised individuals (ITT population), a high number (As indicated by pill counting and the Morisky score [Also, interference with traits of metabolic syndrome with alteration in anti-diabetic (metformin, sitagliptin), anti-lipemic and anti-hypertensive medication during the intervention period could be excluded.The reduction in the primary parameter, ∆BFM, of −0.74 kg in the Probiotic group compared with the Placebo group was moderate and within the range (−0.96 kg; 95% CI −1.21 to −0.71) found in the meta-analysis of the studies reporting on this parameter [In line with the reduction in BFM by the probiotic, there were better outcomes in visceral adipose tissue, as assessed with BIA; body weight; BMI; waist circumference; WHtR; visceral adipose tissue, as assessed with sonography; and in liver steatosis grade, as assessed with sonography. The reduction in body weight of −1.06 kg compared with the Placebo group was within the range (−0.94 kg; 95% CI −1.17 to −0.70) found in a meta-analysis of the studies reporting on this parameter [The somewhat more pronounced reduction in fasting glucose levels and HOMA-IR in the Probiotic group compared with the Placebo group did not attain the significance level (The significantly more pronounced reduction in liver steatosis grade, as assessed with sonography, in the Probiotic group compared with the Placebo group is in line with the reduction in liver enzymes indicating liver steatosis (ALT and AST), although it did not attain the level of statistical significance. This may have been due to the fact that most individuals started with baseline levels within the normal range. In patients with NAFLD, liver enzymes were reduced by probiotics according to the meta-analyses by Koutnikova et al., 2019, and Xiao et al., 2019 [The mean level of the inflammatory marker CRP was also only slightly above the normal range. This may explain why the nominally more pronounced reduction in the Probiotic group compared with the Placebo group did not attain the level of statistical significance. In fact, low-grade inflammation was suggested to drive hyperphagia by attenuating CCK-induced satiation, and dysregulation of anorexigenic and orexigenic hormones expressed in vagal afferent neurons [The effect on BFM, BMI, body weight and visceral adipose tissue of the probiotic strains used in this study was evidently exerted in spite of a non-significant reduction in CRP. Taking the sample size into account, this does not exclude an effect via this mechanism. However, other mechanisms of reduction in BFM and overweight by probiotics have been suggested, such as induction of butyrate and GLP-1 [The reduction in constipation, as assessed with the GSRS, in the Synbiotic group compared with the Placebo group may be explained by dietary fibre and the prebiotic effect, respectively. The synbiotic also resulted in better outcomes in visceral adipose tissue and liver steatosis grade, as assessed with sonography, but all other parameters did not significantly improve. The combination of 