The long-term success of metabolic and bariatric surgery (MBS) depends largely on adherence to health-promoting behaviour following MBS. Especially, adherence to healthy dietary behaviour in line with guidelines appears to be of the utmost importance. The primary objective of the present study is to evaluate the effect of adherence to dietary behaviour recommendations and the percentage of total weight loss (%TWL) after MBS. Adherence is hypothesised to have a positive influence on the %TWL, 24 months after MBS. Furthermore, we investigate the association of various sociodemographic, organisational, psychological and behavioural factors prior to and after MBS and their effect on %TWL.

The present study is a single-centre observational, prospective, longitudinal cohort study conducted in Germany. Data are collected at nine measurement points (T0: 4 weeks prior to MBS; T1: 2 weeks after MBS, T2: 5 weeks after MBS; T3: 3 months after MBS; T4: 6 months after MBS; T5: 12 months after MBS; T6: 18 months after MBS; T7: 24 months after MBS; and T8: 36 months after MBS). Adherence to dietary behaviour recommendations is assessed using the Dietary Behavior Inventory-Surgery (DBI-S). N=325 patients applying for MBS will be included in the study. A regression analysis approach is chosen to answer the primary research question. The primary outcome %TWL is regressed at T7 (24 months after MBS) in a causal analysis on dietary adherence (DBI-S score) at T3–T7, with the covariates age, gender, marital status, educational attainment, employment status, Patient Health Questionnaire-4 score and body mass index at T0 and MBS method at T1. Stepwise hierarchical regression analyses are performed and analysed for significant model differences using ² difference tests. Effect sizes are estimated by R². Group differences are analysed using t-tests and Analyses of variance (ANOVAs). Bivariate correlations of continuous variables are examined using regression/correlation analyses.

The Ethics Committee of the Medical Faculty of the University of Essen-Duisburg has approved the conduct of the study (24-11969-BO). Results will be disseminated through manuscripts in clinical/academic peer-reviewed journals, presentations at academic conferences and communications with partners, participants and other stakeholders. Key findings will also be published in lay language on a publicly accessible website and disseminated via various (social) media channels.

The study has been prospectively registered on 8 October 2024 in the German Clinical Trials Register (DRKS00034888).

Combined vascular endothelial growth factor/programmed death-ligand 1 blockade through atezolizumab/bevacizumab (A/B) is the current standard of care in advanced hepatocellular carcinoma (HCC). A/B substantially improved objective response rates compared with tyrosine kinase inhibitor sorafenib; however, a majority of patients will still not respond to A/B. Strong scientific rationale and emerging clinical data suggest that faecal microbiota transfer (FMT) may improve antitumour immune response on PD-(L)1 blockade. Early trials in melanoma with FMT and reinduction of immune checkpoint blockade (ICI) therapy in patients with anti-PD-1-refractory metastatic melanoma were reported in 2021 and demonstrated reinstatement of response to ICI therapy in many patients. Due to anatomical vicinity and the physiological relevance of the gut-liver axis, we hypothesise HCC to be a particularly attractive cancer entity to further assess a potential benefit of FMT in combination with ICI towards increased antitumour immunity. Additionally, HCC often occurs in patients with liver cirrhosis, where liver function is prognostically relevant. There is evidence that FMT may increase hepatic function and therefore could positively affect outcome in this patient population.

This prospective, multicentre, randomised, placebo-controlled, double-blind phase II clinical trial has been designed to assess immunogenicity and safety of FMT via INTESTIFIX 001 combined with A/B in advanced HCC in comparison to A/B with placebo. Primary endpoints are measured as tumour CD8+ T cell infiltration after 2 cycles of treatment with vancomycin, A/B+INTESTIFIX 001 in comparison to vancomycin-placebo, A/B+INTESTIFIX 001-placebo and safety of the therapeutic combination in advanced HCC. INTESTIFIX 001 is an encapsulated FMT preparation by healthy donors with a high alpha-diversity in their gut microbiome for oral administration, manufactured by the Cologne Microbiota Bank (CMB). Sample size was calculated to achieve a specific expected accuracy for the primary immunological endpoint. 48 subjects will be randomised to reach a goal of 42 usable measurements in the modified intention-to-treat set. Subjects will be randomised in a 2:1 ratio to A/B or placebo (28 A/B, 14 placebo).

The study was approved by ethics committee review and the German Federal Ministry of Drugs and Medical Devices. The trial is registered under EU CT no. 2023-506887-15-00. The outcome of the study will be disseminated via peer-reviewed publications and at international conferences.

NCT05690048.