Introducing the TASTY trial – learn more about our approach to investigating the triad of nutrition, gut microbiota and rheumatoid arthritis
A new publication was released by the ENDOTARGET consortium describing the protocol of our TASTY study, which aims to investigate whether a dietary intervention based on a typical Mediterranean Diet enriched with fermented foods can impact the gut microbiota, intestinal permeability, and rheumatoid arthritis (RA)‑related outcomes. This protocol was published in April 2025 in the Nutrition Journal from BMC. Authors of this protocol are: Sofia Charneca, Ana Hernando, Inês Almada-Correia, Joaquim Polido-Pereira, Adriana Vieira, Joana Sousa, Ana Santos Almeida, Carla Motta, Gonçalo Barreto, Kari Eklund, Ana Alonso-Pérez, Rodolfo Gómez, Francesco Ciccia, Daniele Mauro, Salomé S. Pinho, João Eurico Fonseca, Patrícia Costa-Reis, and Catarina Sousa Guerreiro.
Why do we think the TASTY study is so important?
An imbalance in the composition and function of the gut microbiota, referred to as gut dysbiosis, has been implicated in the onset and progression of RA. The mechanism whereby this may occur is related to the influence of dysbiosis in disrupting the integrity and function of the intestinal barrier, as well as mucosal immunity. Increased intestinal permeability facilitates the translocation of bacteria and their components into the blood circulation, leading to endotoxemia and thus possibly contributing to the inflammatory process causing RA. Since diet is recognised as a key environmental factor influencing the gut microbiota, nutritional interventions targeting RA activity are currently being explored. This protocol describes a study that aims to decipher these relationships. This way, we want to bridge the existing gap between nutrition-related knowledge and disease pathogenesis and activity in RA. Further, this protocol can serve as a kind of guideline for other diet trials.
What does the TAST Study look like?
The TASTY study is an ongoing single-centre randomised controlled trial investigating whether a nutritional intervention based on a Mediterranean Diet enriched with fermented foods (MedDiet+) may influence disease activity, functional status, quality of life, intestinal permeability, endotoxemia, inflammatory biomarkers, gut and oral microbiota, serum proteomics and serum glycome.
100 patients with RA are being recruited at Unidade Local de Saúde (ULS) Santa Maria in Lisbon, Portugal, and randomly assigned to either the intervention (MedDiet+) or the control group. The 12-week nutritional intervention includes a personalised dietary plan following the MedDiet+ pattern, along with educational resources, food basket deliveries, and clinical culinary workshops, all developed and monitored weekly by registered dietitians.
How is the MedDiet+ group treated?
At baseline, a personalised nutritional plan is elaborated for each participant, and its implementation is closely monitored through weekly follow-up calls and monthly face-to-face appointments. Educational food baskets are delivered weekly with different typical ingredients of the MedDiet+ pattern to encourage their inclusion in the patients’ daily meals. Educational content consists of video recordings and two recipe books to share new ideas for cooking recipes, as well as educational and useful content to help participants meet the nutritional recommendations. Finally, access to an online clinical culinary workshop is provided. The clinical culinary workshop allows for the application of the provided nutritional knowledge into culinary preparations through the demonstration of recipes and culinary methods.
How is the Control group treated?
At baseline, the control group receives a flyer with general recommendations on a healthy diet, based on the Portuguese brief guidance for healthy eating in primary health care. No food baskets or any of the nutritional education strategies are implemented. To promote study adherence, a shopping voucher is given to each participant at the end of the trial. This comparator was chosen to reflect the standard of care that could be given by clinicians.
What kind of data is collected?
- Sociodemographic and lifestyle data is collected via the electronic hospital records of each patient and a structured questionnaire.
- Nutritional assessment, encompassing (i) nutritional intake, (ii) dietary pattern characterisation, (iii) body composition analysis, and (iv) anthropometric measures, is performed at baseline and at the end of the trial for both groups and every month for the intervention group.
- Clinical outcome measures include (i) the disease activity score in 28 joints calculated with erythrocyte sedimentation rate (DAS28-ESR) scoring system, (ii) articular ultrasound examination for grey scale and power doppler in 32 joints, (iii) functional status assessed through the Health Assessment Questionnaire (HAQ) and (iv) quality of life assessed through the Short Form 36 Health Survey Questionnaire (SF-36). Clinical assessments are performed at baseline and after 12 weeks in both groups.
- Saliva and stool samples are collected and processed to assess the oral and gut microbiota. In addition, faeces samples are also used to measure faecal calprotectin concentrations.
- Blood samples are collected to determine lipid profile and inflammation markers.
- Urine samples are used to assess intestinal permeability by the lactulose/mannitol test.
- Endotoxemia is assessed by analysing the LPS biological activity with an in vitro test for TRL-4 activation using the serum of the participants.
- Blood serum is used to perform proteomic analysis, glycome analysis (chromatographic methods), and to analyse indirect markers of intestinal permeability.
Why do we believe that we and the society will benefit from the study?
In the past, several trials have shown that the Mediterranean Diet (MedDiet) can positively influence the gut microbiota composition and has anti-inflammatory and antioxidant properties. Although the TASTY study is still ongoing, it is expected that enriching the traditional MedDiet with fermented foods will further enhance these effects.
Among all other reported studies encompassing dietary interventions, the TASTY trial stands out for its innovative approach, combining a well-established health-promoting dietary pattern with specific components designed to promote beneficial microbiota modulation. This trial also includes a dynamic set of educational resources to improve literacy, compliance, and empower participants to make better food choices. Another differentiating characteristic of the TASTY trial is its extensive data collection and comprehensive biomarker analysis. Further, the TASTY study goes beyond merely providing a dietary plan, addressing a key limitation in previous dietary trials: participants’ difficulty in adhering to recommendations. Several nutritional education strategies are implemented based on the “Clinical Culinary” concept to ease the process of changing eating habits and maximise the effects of the nutritional intervention. The main goal of this approach is to promote a positive behavioural change by equipping patients with the knowledge and practical skills needed to improve their health.
The trial will also allow to address if significant differences in dietary intake and clinical outcomes may be achieved by standard care that could be given by clinicians (control group) and to which degree a structured nutritional plan developed by registered dietitians (MedDiet+) implies additional benefits. Weaknesses of this trial include the inability to observe long-term effects beyond the intervention period and the reliance on self-reported food intake, which is susceptible to inaccuracies. However, the close follow-up during the intervention period, along with the educational and patient empowerment strategies, was designed to mitigate these limitations.
Read the full publication: Tasty trial: protocol for a study on the triad of nutrition, intestinal microbiota and rheumatoid arthritis
Glossary
Biomarker: a measurable biological indicator (e.g., a molecule, gene, or physiological characteristic) that provides information about a biological process, disease state, or response to treatment.
Clinical Culinary: a concept that combines culinary principles with medical and nutritional science to develop dietary strategies that support disease prevention, management, and overall health.
Disease Activity Score in 28 joints calculated with erythrocyte sedimentation rate (DAS28-ESR): a clinical measure used to assess disease activity in RA by evaluating 28 joint counts for tenderness and swelling, along with the patient’s general health assessment and the erythrocyte sedimentation rate as an inflammatory marker.
Dysbiosis: an imbalance in the composition or function of the microbiota, which can contribute to inflammation, disease development, and disruptions in overall health.
Endotoxemia: a condition characterised by the presence of endotoxins, primarily lipopolysaccharides from Gram-negative bacteria, in the bloodstream, leading to systemic inflammation and potentially contributing to various chronic diseases.
Endotoxin: a toxic component of the outer membrane of Gram-negative bacteria, primarily lipopolysaccharides, which can trigger strong immune responses and inflammation.
Erythrocyte sedimentation rate (ESR): a blood test that measures how quickly red blood cells settle at the bottom of a test tube over a specified period.
Glycome: the complete set of glycans (complex carbohydrates) present in a cell, tissue, or organism, playing a crucial role in biological processes such as cell signaling, immune response, and disease development.
Health Assessment Questionnaire (HAQ): a standardised patient-reported tool used to measure functional ability, disability, and quality of life, particularly in individuals with rheumatic diseases like rheumatoid arthritis.
Lipid: a broad class of hydrophobic or amphipathic organic molecules, including fats, oils, phospholipids, and steroids, that play essential roles in energy storage, cell membrane structure, and signaling processes in living organisms.
Lipopolysaccharide (LPS): a large molecule found in the outer membrane of Gram-negative bacteria, composed of lipids and polysaccharides, that acts as an endotoxin and can trigger strong immune and inflammatory responses.
Microbiota: a specific community of microorganisms, including bacteria, viruses, fungi, and archaea, residing in a defined habitat, like the human gut or soil.
Proteomics: the large-scale study of proteins, including their structures, functions, interactions, and modifications, to understand biological processes and their roles in health and disease.
Rheumatoid Arthritis (RA): a chronic immune-mediated disorder that primarily affects joints, causing inflammation, pain, stiffness, and eventually joint damage and deformity.
Short Form 36 Health Survey Questionnaire (SF-36): a widely used patient-reported survey that measures overall health status and quality of life across eight domains, including physical functioning, pain, mental health, and general well-being.
Single-center randomized controlled trial: a clinical study conducted at a single location where participants are randomly assigned to different intervention groups to evaluate the effectiveness and safety of a treatment or intervention under controlled conditions.
Toll-like receptor 4 (TRL4): is a protein on the surface of immune cells that recognises specific bacterial molecules and triggers an immune response to defend against infections.
