Postbiotics: what else?

The use of probiotics and synbiotics in the food industry or as food supplements for a balanced diet and improved gut homeostasis has been blooming for the past decade. As feedback from healthy consumers is rather enthusiastic, a lot of effort is currently directed in elucidating the mechanisms of interaction between beneficial microbes and barrier and immune function of the host. The use of probiotics or synbiotics for treating certain pathologies has also been examined, however, the outcome has not always been favourable. In most cases, the effect of the administered probiotic is evident when the bacteria are still alive at the time they reach the small and large intestine, suggesting that it is dependent on the metabolic activity of the bacteria. Indeed, in some occasions it has been shown that the culture supernatant of these bacteria mediates the immunomodulatory effect conferred to the host. Recent work on relevant probiotic strains has also led to the isolation and characterisation of certain probiotic-produced, soluble factors, here called postbiotics, which were sufficient to elicit the desired response. Here, we summarise these recent findings and propose the use of purified and well characterised postbiotic components as a safer alternative for clinical applications, especially in chronic inflammatory conditions like inflammatory bowel disease, where probiotics have not yet given encouraging results as far as induction of remission is concerned.

Gadd45α activity is the principal effector of Shigella mitochondria-dependent epithelial cell death in vitro and ex vivo.

Modulation of death is a pathogen strategy to establish residence and promote survival in host cells and tissues. Shigella spp. are human pathogens that invade colonic mucosa, where they provoke lesions caused by their ability to manipulate the host cell responses. Shigella spp. induce various types of cell death in different cell populations. However, they are equally able to protect host cells from death. Here, we have investigated on the molecular mechanisms and cell effectors governing the balance between survival and death in epithelial cells infected with Shigella. To explore these aspects, we have exploited both, the HeLa cell invasion assay and a novel ex vivo human colon organ culture model of infection that mimics natural conditions of shigellosis. Our results definitely show that Shigella induces a rapid intrinsic apoptosis of infected cells, via mitochondrial depolarization and the ensuing caspase-9 activation. Moreover, for the first time we identify the eukaryotic stress-response factor growth arrest and DNA damage 45α as a key player in the induction of the apoptotic process elicited by Shigella in epithelial cells, revealing an unexplored role of this molecule in the course of infections sustained by invasive pathogens.