4. Discussion
obesity, Tax4Fun2, T2D, Adiposity, diabetes
OBESITY, DISEASE, ADIPOSITY, DIABETES
The relationship between probiotic supplementation and glycemic control in T2D is quite complex and has not been adequately investigated, especially in longer term studies of at least 6 months duration and with HbA1c as the primary endpoint. Most studies have focused on <12 weeks’ evaluation so far, using different strains of probiotics, in different countries, and focusing more on fasting blood glucose, which probably does not allow sufficient time for an effect to be seen and does not give a good index of general glycemic control. Furthermore, the relationship between probiotic administration and the gut microbiome has not been consistently explored. This gap in research may explain the various results that have been found in the literature thus far [The most significant finding involved the effects of probiotic supplementation on glycemia. The analysis of HbA1c values (the primary endpoint of the study), adjusted for changes in waist circumference, revealed compelling insights (The glycemic findings of the present study align with recent umbrella meta-analyses investigating the impact of probiotic supplementation on glycemic control [The findings of the favorable impact of probiotics on total cholesterol in the present study are consistent with the broader literature, although exceptions exist [Adiposity measures were also improved with probiotic treatment in the present study, corroborating results in the literature that probiotics can have beneficial effects on obesity, both in healthy subjects [The potential mechanisms by which probiotic supplements may exert beneficial effects in people with diabetes are complex and not fully understood. However, several hypotheses and mechanisms have been proposed. Probiotics are live microorganisms that, when consumed, can influence the composition and balance of the gut microbiota [Previous studies have recorded many changes in the gut microbiota of T2D individuals, as analyses in gut microbial composition have shown that patients with T2D are characterized by a moderate degree of gut microbial dysbiosis, a reduction in the abundance of some bacteria and an increase in various pathogens [Although no statistically significant differences were observed in α and β diversity of the examined gut microbiome, several genera, metabolites, and key enzymes associated with diabetes were found to be influenced by the six-month administration of probiotics. Furthermore, it is worth noting that obesity has been proven to be a complex factor influencing the microbiome [The Tax4Fun2 analysis conducted on the placebo and intervention groups yielded intriguing findings with implications for diabetes. The microbial functional analysis revealed significant dysregulation in several key enzymes. Notably, substantial disparities were observed between the placebo and intervention groups, indicating a behavioral and metabolic shift in the microbiota to adapt to their microenvironment and ensure survival. The placebo group exhibited an augmented presence of microbial metabolites associated with survival, such as the GntR family transcriptional regulator [One notable strength in the present study was the clear documentation of medication use. This was crucial because certain anti-diabetic medications, such as metformin [The duration of probiotic intervention can significantly impact glycemic control, with longer interventions often yielding better results [The strengths of the present study are its relatively long-term follow-up, its random, double-blind distribution of participants with stable lifestyle/dietary and medical treatment over the course of the study, and the fact that stool microbial analysis was performed, aiming to identify differences in microbial composition mediated by the disease and the intervention. However, this study had some limitations as well. The participant sample size, particularly in the microbiome sub-study, was not large, and there was a relatively high dropout rate of 32.6%, primarily due to withdrawal of consent. This issue is not unique to this study, as other probiotics trials have also encountered similar dropout rates [