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Linking Intestinal Bacteria and Host Metabolism to Tackle Type 2 Diabetes with Novel Food

Periodic Reporting for period 1 - DiBaN (Linking Intestinal Bacteria and Host Metabolism to Tackle Type 2 Diabetes with Novel Food)

Período documentado: 2024-10-01 hasta 2025-09-30

Type 2 diabetes (T2D) is characterised by insulin resistance or insufficient insulin production, resulting in high blood glucose levels. An imbalance in the intestinal microbiota (intestinal dysbiosis) is one factor driving the progression of insulin resistance to T2D. Furthermore, intestinal dysbiosis is linked to poor nutrition. The EIC-funded DiBaN project aims to fight dysbiosis and T2D using novel nutrients prepared from ‘metabolically healthy’ insects to promote a healthy microbiome-host metabolic interface. To do so, they will develop advanced ex vivo platforms faithfully simulating in vivo dysbiosis and insulin resistance to overcome current limitations in nutrient testing. An AI-based application using the project’s data should be able to predict individuals’ responses to nutritional interventions.
Technical activities performed so far can be summarized as follows:

WP1. CCMAR cultured 10 microalgae strains, following biomass production, each strain palatability was tested for A. domesticus fed. Three strains were identified as promising candidates to enhance the nutritional profile of A. domesticus. To promote the sustainable use of the biomass and minimise waste, the strains were subjected to biorefinery processing to generate different extracts with potential for various applications. The biochemical composition, bioactivity and toxicity of each extract or ingredient was characterised.

WP2. Following on the microalgae palatability test on A. domesticus, a dose-response assay with the three selected microalgae, provided by CCMAR, was performed by NUTRINSECT. The nutritional composition of the resulting A. domesticus flour was analized, and based on the results optimal feeding doses and best performing microalgae was selected at a feeding rate of 12-15%. UAM-CIAL prepared and analysed A. domesticus meals, oils and extracts for novel food development testing their antioxidant capacity. The best extracts based on their profile were sent to CSIC-IIBM for testing in cell-based assays.

WP3. CSIC-IIBM designed with the support of the specialized company SAFE two basic diets for mice one to include the A. domesticus flour (60% Relative Protein content derived from A. domesticus flour) and a balanced control diet. The first tolerance test in mice is currently ongoing.
IMDEA Nutrition launched the human intervention study in September 2025 and is currently ongoing.

WP4. IIBM-CSIC has set up the culture of mouse and human intestinal organoids. A choice of A. domesticus extracts prepared by UAM-CIAL are being tested by IIBM-CSIC in relevant cell culture systems for metabolic control and type 2 diabetes (T2D) development. In vitro pre-digested A. domesticus flour is currently being tested by IIBM-CSIC and IMDEA Nutrition in relevant cell culture systems for metabolic control and type 2 diabetes (T2D) development.
We have advanced during the first reporting period beyond the state of the art in the following in topics:

1. The setting up of the ex-vivo and in vivo models monitorization, from which the data to be integrated.

2. The setting up of the reference ex-vivo bacterial (E. coli) culture and on the technical aspects of the monitorization of bacterial (E. coli) responses in vivo.

3. The improvement of A. domesticus in two fronts, on one hand by supplementing its diet with microalgae and on the production work flow of the flour per se. So, improving significantly its quality, nutritional value and shelf live. Furthermore, a new procedure for A. domesticus extract preparation has been developed and some of the resulting extracts that are showing promising probiotic activities based on in vitro assays, are now being tested in cell-based system assays that have confirmed anti-inflammatory and insulin sensitizing effects.

4. We have implemented the generation of intestinal organoids (IOs) from mice and humans, starting the collection of a human biobank for the testing of personalized responses. We are also performing the preparatory work on bacteria (E. coli) cultures ex-vivo to go for the next step of exposing the organoids to bacterial cultures. The validation of the models is also ongoing, we have optimized the methodology to follow up bacterial (E. coli) responses in vivo. We also started the first intervention study with mice that will provide the validation data for the mouse IOs responses.

5. We have selected one microalgae strain to supplement A. domesticus fed, expected to improve A. domesticus flour as a source of derived products enriched in bioactive molecules. A new biorefinery process for microalgae has been developed and interesting by-products obtained. The best of them in terms of bioactivity will be further tested for A. domesticus fed supplementation.

The evaluation of the microalgae derived products on mammalian systems was not contemplated in the proposal even though they by themselves could have significant value as food supplements or food ingredients for human consumption. It would thus be of interest to boost the Impact of the project to get some complementary funding in this regard.
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