Regarding this aspect, it should also consider that the TLR-4 function and expression are modulated not only by genetic variants and haplotypes1,9,36, but also by environmental factors (such as diet37, mite allergens and air pollution38), and their cross-interaction with microbiota37, which may remain in a healthy state or show alterations (i.e. dysbiosis and consequent endotoxemia associated with age or obesity)39 and consequent epigenetic changes40. Here, TLR4 is linked to obesity due to melanocortin 4 receptor deficiency.