The present study aimed to compare the absorption and transport patterns of three main betalains, betanin, vulgaxanthin I and indicaxanthin, into intestinal epithelial cells and to assess their distinct molecular effects on inflammatory and redox-related cell signalling in association with their radial scavenging potencies. All three betalains showed anti-inflammatory effects (5–80 μM), reflected by attenuated transcription of pro-inflammatory mediators such as cyclooxygenase-2 and inducible NO-synthase. Concomitant increases in antioxidant enzymes such as heme oxygenase-1 were only observed for betanin. Moreover, betanin uniquely demonstrated a potent dose-dependent radical scavenging activity in EPR and cell-based assays. Results also indicated overall low permeability for the three betalains with P_app of 4.2–8.9 × 10⁻⁷ cm s⁻¹. Higher absorption intensities of vulgaxanthin and indicaxanthin may be attributed to smaller molecular sizes and greater lipophilicity. In conclusion, betanin, vulgaxanthin I and indicaxanthin have differentially contributed to lowering inflammatory markers and mitigating oxidative stress, implying the potential to ameliorate inflammatory intestinal disease. Compared with two betaxanthins, the greater efficacy of betanin in scavenging radical and promoting antioxidant response might, to some extent, compensate for its poorer absorption efficiency, as demonstrated by the Caco-2 cell model.

With the advancement of high-resolution techniques and multi-omics strategy, health implications of probiotics are investigated more profoundly, with the focus shifting from live microbial functions to their non-viable, health-beneficial byproducts, referred to as postbiotic components. Emerging evidence suggests these compounds are promising for non-invasive strategies to prevent and treat chronic diseases. Nonetheless, the understanding of their in vivo effects and mechanisms of action still awaits deeper and holistic exploration. This review presents an up-to-date overview of research on the bioactivities of postbiotic components, elucidating how they orchestrate intestinal homeostasis and systemic health via multi-directional communications. It further highlights the downstream metabolic consequences of typical bioactives by fostering crosstalk between gut and the liver, cardiovascular, and neural system. Finally, it outlines current challenges and future directions of research. These intricate interactions underscore that the gut serves not only as a digestive organ but also a nexus influencing physiological and pathological processes through the body. Compounds derived by probiotics are key drivers of intestinal homeostasis and powerful regulators of the physiology of distant organs. With further clinical investigations, they hold promise for establishment of novel postbiotic-targeted therapies to address health challenges in the future.