## 4 Discussion
In the context of oncology, it works as a protective mechanism against tumor aggressiveness and exhibits antitumor activity [29]. However, in cases of imbalance of the microbiota, such as in cases of marked adiposity, intestinal dysbiosis will develop. This dysbiosis compromises intestinal bioactivity and increases the abundance of inducing species (pathogenic bacteria) which can cause inflammatory bowel diseases and cancer [26]. Conversely, specific probiotic bacterial strains have the capacity to generate butyrate and lactate, two metabolites derived from the production of short-chain fatty acids (SCFAs) important for metabolic protection against cancer [30]. These SCFA metabolites are fermented acids produced by Gram-positive bacteria of the intestinal microbiota and are recognized as microbiota-derived metabolites capable of improving intestinal barrier immunity, promoting the production of adhesion molecules, deterring invaders, and reducing host intestinal inflammation [31]. SCFAs are essential regulators for the recruitment, activation, and differentiation of various immune cells such as dendritic cells (CDs), neutrophils, macrophages, and lymphocytes. Additionally, they also play a pivotal role in regulating the expression of (i) pro-inflammatory cytokines, such as IL-12 and IL-6, and (ii) anti-cytokines' association between SCFAs and receptors coupled to G proteins, for example, GPR109a associated with CD, which results in an increased expression of IL-10 and a reduction in IL-6 [32]. Consequently, this leads to the expansion of T-regulatory cells, which, in turn, inhibit the proliferation of Th17 cells, indicating their crucial role in anti-inflammatory pathways such as apoptosis, especially in inflammation-induced colorectal cancer [29; 32; 33]. Probiotics have the potential to modulate the immune system, either at the gut level or systematically, and offer other therapeutic benefits such as improving lactose tolerance, reducing inflammation, and exhibiting antioxidant properties [34]. The imbalance between the production of pro-oxidative molecules (reactive oxygen species (ROS) and reactive nitrogen species (ERN)) and the efficiency of antioxidation defenses is one of the factors associated with CCR [30]. The oxidative stress produced by the dysbiotic intestinal microbiota promotes the stimulation of chronic inflammation through the production of ROS that induce DNA damage, activation of oncogenes, and inactivation of tumor suppressor genes [30,35]. Within mammalian cells, glutathione is the main low-molecular-weight intracellular thiol that plays a critical role in defending against oxidative and nitrosative stress. Reduced glutathione levels have been detected in the early stages of apoptosis, and the identification of these values by simple in vitro assays allows for the detection of changes in total glutathione in apoptosis and other contexts [36]. Our research showed a heterogeneous trend in the conditions with the use of the PPARy agonist used for optimizing adipogenesis. Recent studies have supported the fact that this class of antidiabetic drug, specifically thiazoltionedes, may be associated to a modest 9% reduction in the risk of developing CRC in patients with T2 DM treated with Piogltazone [37]. Despite Piogltazone being directed to reduce insulin resistance, its use can still increase the accumulation of lipid droplets in mature adipocytes and activate tumor suppression pathways by apoptosis, such as the mTOR pathway, for example [38]. Our results evidenced that using Piogltazone promotes protection activity in colorectal tumor cells exposed to the adipose microenvironment (Figure 5). A study by [PERSON] et al. (2014) evaluated the effect of Piogltazone on five tumor cell lines (Capan-1, Aspc-1, BxPC-3, PANC-1, and MIApaCa-2), and the results confirmed an inhibitory effect on the proliferation of all five examined cell lines when the concentration of Piogltazone exceeded 10 \(\upmu\)M [39,40]. In summary, high levels of PPARy expression have been associated with cell proliferation.