A randomised placebo controlled trial of VSL#3® probiotic on biomarkers of cardiovascular risk and liver injury in non-alcoholic fatty liver disease

Abstract

Background Non-alcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular risk irrespective of conventional risk factors. The role of gut-liver interaction is implicated in its development. We investigated the effects of VSL#3® probiotic supplementation on biomarkers of cardiovascular risk and liver injury in patients with NAFLD. Methods A randomised, double-blinded, placebo-controlled, proof-of-concept study was undertaken. Patients with NAFLD were randomly allocated to take 2 sachets VSL#3® probiotic or placebo twice daily for 10 weeks. Measurements of endothelial function (digital photoplethysmography, sVCAM-1 and cGMP), oxidative stress (glutathione ratio and LHP), inflammation (hsCRP), insulin resistance (HOMA-IR) and liver injury [transaminases, fibrosis risk score and acoustic structure quantification (ASQ)] were undertaken before and after intervention. Difference in baseline characteristics between the treatment groups was analysed using independent t-test or Mann Whitney U test for non-parametric data. Independent t-test was used to compare the outcomes at the end of the study between the two treatment groups. Wilcoxon Signed Rank test was used to determine the difference in fibrosis risk scores before and after treatment. Spearman’s correlation was used to determine any association between cardiovascular and hepatic markers at baseline. Results Thirty-five patients completed the study (28 males and 7 females) with a mean age of 57 ± 8 years, body mass index of 32.6 ± 5.0 kg/m2 and a relatively short duration of NAFLD (median duration 0.3 IQR 2.0 years). No significant difference was observed in biomarkers of cardiovascular risk and liver injury following VSL#3® supplementation. Significant correlations were noted between sVCAM-1 and hsCRP (rho = 0.392, p = 0.01), and HOMA-IR and AST (rho = 0.489, p < 0.01) at baseline. Conclusions This is the first study to evaluate the effect of VSL#3® on ASQ in patients with NAFLD. VSL#3® did not significantly improve markers of cardiovascular risk and liver injury in patients with NAFLD. However, the study supports an association between endothelial dysfunction and inflammation in patients with NAFLD and suggests that NAFLD is linked with insulin resistance. Trial registration: ISRCTN05474560 (https://doi.org/10.1186/ISRCTN05474560) Registered 9 August 2012 (retrospectively registered).

Probiotic Therapy With VSL#3® in Patients With NAFLD: A Randomized Clinical Trial

“…In literature, a previous proof-of-concept study conducted on a little number of patients was undertaken showing that VSL#3 ® did not significantly improve the markers of cardiovascular risk and liver injury in patients with NAFLD after 10 weeks of treatment. However, the study supports an association between endothelial dysfunction and inflammation in patients with NAFLD ( 10 ). On this basis, we projected a larger and longer study aimed to evaluate if a supplementation with VSL#3 ® [a high-concentration multi-strain probiotic mix containing one strain of Streptococcus thermophilus BT01, three strains of Bifidobacteria ( B. breve BB02; B. animalis subspecies [subsp.]…”

Usefulness of Probiotics in the Management of NAFLD: Evidence and Involved Mechanisms of Action from Preclinical and Human Models

“…In addition, similar hepatoprotective effects were also described in a study in which probiotics were administered mixed in a yogurt, instead as a supplement (capsule or sachet) [ 59 ]. Nevertheless, there are also studies in which the administration of probiotics did not result in the improvement of markers of liver injury in patients with NAFLD, despite the fact that the doses used and the administration periods were similar to those studies in which significant improvements were reported ( Table 3 ) [ 60 , 61 ]. In this regard, according to Mohamed Nor et al [ 60 ], the reduced sample size, along with the apparent higher variability of Malaysians’ gut microbiota composition (due to a more diverse dietary intake), may have influenced the obtained results.…”

“…Nevertheless, there are also studies in which the administration of probiotics did not result in the improvement of markers of liver injury in patients with NAFLD, despite the fact that the doses used and the administration periods were similar to those studies in which significant improvements were reported ( Table 3 ) [ 60 , 61 ]. In this regard, according to Mohamed Nor et al [ 60 ], the reduced sample size, along with the apparent higher variability of Malaysians’ gut microbiota composition (due to a more diverse dietary intake), may have influenced the obtained results. Moreover, the authors also pointed to a change in dietary fat observed in the group receiving the probiotic, which could have somehow blunted the potential beneficial effects of the probiotic intervention [ 60 ].…”

“…In this regard, according to Mohamed Nor et al [ 60 ], the reduced sample size, along with the apparent higher variability of Malaysians’ gut microbiota composition (due to a more diverse dietary intake), may have influenced the obtained results. Moreover, the authors also pointed to a change in dietary fat observed in the group receiving the probiotic, which could have somehow blunted the potential beneficial effects of the probiotic intervention [ 60 ]. As far as the study carried out by Chong et al [ 61 ] is concerned, differences in baseline characteristics between the probiotic and the placebo groups, as well as the impossibility to determine the participants’ NAFLD severity, were pointed out by the authors as potential factors influencing the outcomes of the study.…”

Sex Differences in Cardiovascular Impact of Early Metabolic Impairment: Interplay between Dysbiosis and Adipose Inflammation

“…It did not appear to improve cardiovascular risk factors and liver injury scores. Nevertheless, it improved HOMA-IR (Chong et al, 2021). Another randomized controlled cross-over study showed that metabolic syndrome symptoms were not alleviated by a daily intervention with Lactobacillus reuteri V3401 strain for 12 weeks.…”