Future research should address several points: (i) longitudinal studies to determine whether LPS and zonulin levels normalize after smoking cessation or switching from HTPs to abstinence; (ii) microbiome sequencing to identify specific bacterial taxonomy involved; (iii) mechanistic studies linking LPS-TLR4 signaling to NOX2 activation and cardiovascular outcomes; and (iv) interventional trials testing whether microbiota-targeted therapies can mitigate smoke-induced endotoxemia. Here, TLR4 is linked to serum lipopolysaccharide activity.