## 3 Results
### Stability Test of the Innovative Symbiotic Formulation  
A first innovative symbiotic, named NatuREN P, was constituted as follows:  
* _B. animalis_ BLC1 (ca. 0.24 g = 10\({}^{9}\) cells);
* _Lc. casei_ LC4P1 (ca. 0.24 g = 10\({}^{9}\) cells);
* FOS (2.5 g);
* Inulin (2.5 g);
* Pomegranate seed extract (0.2 g);
* Maltodext from corn (0.5 g);
* Sodium cyclamate (0.01 g).  
As reported above, the initial cell density of the probiotic strains was about 9 log CFU/g of lyophilized cells (minimum daily dose referring to each individual strain). To ascertain the survival of strains in the formulation, their cell density was estimated. The results showed that the cell density of probiotics underwent a decrease of one or more logarithmic cycles after 2 months at both room (20/30 \({}^{\circ}\)C) and refrigerated (2/8 \({}^{\circ}\)C) temperature.  
As Indigo, ResTom, and Bronze are transgenic varieties and their use is, therefore, limited to studies in mouse models, we searched for a mixture of phenolic compounds approaching the profiles of polyphenols and antioxidants of transgenic tomato varieties. Our previous results [27; 34] showed that 10% red grape skin extract was able to reduce intestinal  
Figure 8: Concentrations of short-chain fatty acids (SCFAs; ppm equivalents) produced by four probiotic strains after 24 h of growth in fecal media obtained from feces of HC patients with the addition of FOS and inulin (2.5 g/L each). A sterilized fecal medium without the addition of bacterial cells was used as the control. Data are reported as the average of one technical triplicate \(\pm\) SD. \({}^{\text{a-d}}\) Among same metabolite, different superscript letters showed a significant difference (\(p<0.05\)).  
inflammation in a colitis mouse model. Based on the polyphenol profiles of Bronze tomato and red grape skin (Supplementary Table S3), we decided to use a polyphenol mixture (named Polimix), simultaneously approaching the polyphenols content of Bronze tomato and red grape skin extract. More specifically, Polimix includes quercetin, resveratrol, and proanthocyanidins in a ratio of 64:23:13. Polimix was added (5 g/L) to artMRS + 2.5 g/L of FOS + 2.5 g/L of inulin, as already performed, to assess the growth of probiotics in the presence of pomegranate seed extract (Pom.S.E.). A control medium without Polimix was used. Acidification and viable cell count of the two best SCFA-producing probiotics (_B. animalis_ BLC1 and _Lc. casei_ LC4P1) were evaluated after 24 h at 37 \({}^{\circ}\)C. The other 17 probiotics reported in Table 1 were only used for comparison. Among bifidobacterial strains, _B. animalis_ BLC1 showed the highest \(\Delta\)pH and a slightly higher cell count than _B. breve_ 15A (Supplementary Figure S1A). Among the lactobacilli, _L. delbrueckii_ SP5 showed the highest \(\Delta\)pH (Supplementary Figure S1A), whereas _Lc. casei_ LC4P1 had the highest cell count (Supplementary Figure S1B).  
Hence, considering the SCFA produced by the 19 probiotics and, in line with the selection criterion previously adopted, a second innovative symbiotic formulation was constituted as follows, and was named NatuREN G:  
* _B. animalis_ BLC1 (ca. 0.24 g = 10\({}^{9}\) cells);
* _Lc. casei_ LC4P1 (ca. 0.24 g = 10\({}^{9}\) cells);
* FOS (2.5 g);
* Inulin (2.5 g);
* Quercetin (0.064 g);
* Resveratrol (0.023 g);
* Grapeseed (_Vitis vinifera L._) powder extract (0.013 g), proanthocyanidins (tit. 95% d.extr.);
* Maltodext from corn (0.5 g);
* Sodium cyclamate (0.01 g).  
In contrast to NatuREN P, in NatuREN G, the probiotics' cell density remained approximately stable after two months of storage at both room (20/30 \({}^{\circ}\)C) and refrigerated (2/8 \({}^{\circ}\)C) temperatures. After 6 months of storage, a slight decrease in cell density was found, but the values of cell density were higher than 8 log CFU/g. The main findings leading to the constitution of NatuREN G are summarized in Table S4.