Protective effects of the postbiotic deriving from cow’s milk fermentation with L. paracasei CBA L74 against Rotavirus infection in human enterocytes

Abstract

Rotavirus (RV) is the leading cause of acute gastroenteritis-associated mortality in early childhood. Emerging clinical evidence suggest the efficacy of the postbiotic approach based on cow’s milk fermentation with the probiotic Lacticaseibacillus paracasei CBAL74 (FM-CBAL74) in preventing pediatric acute gastroenteritis, but the mechanisms of action are still poorly characterized. We evaluated the protective action of FM-CBAL74 in an in vitro model of RV infection in human enterocytes. The number of infected cells together with the relevant aspects of RV infection were assessed: epithelial barrier damage (tight-junction proteins and transepithelial electrical resistance evaluation), and inflammation (reactive oxygen species, pro-inflammatory cytokines IL-6, IL-8 and TNF-α, and mitogen-activated protein kinase pathway activation). Pre-incubation with FM-CBA L74 resulted in an inhibition of epithelial barrier damage and inflammation mediated by mitogen-activated protein kinase pathway activation induced by RV infection. Modulating several protective mechanisms, the postbiotic FM-CBAL74 exerted a preventive action against RV infection. This approach could be a disrupting nutritional strategy against one of the most common killers for the pediatric age.

Evidence on postbiotics in infants and children

“…Considering effects of a heat-inactivated L. paracasei CBA L74 for preventing acute gastroenteritis, further studies were conducted to better understand the underlying mechanisms. A 2022 study [10] found, in an in-vitro model of rotavirus infection in human enterocytes, that heat-inactivated L. paracasei CBA L74 positively modulates a range of nonimmune and immune defense mechanisms against rotavirus infection in human enterocytes. Overall, it contributed to the inhibition of the inflammatory status by reducing the generation of proinflammatory markers such as rotavirus-induced reactive oxygen species (ROS) as well as interleukin (IL)-8, IL-6 and tumour necrosis factor (TNF)-α production.…”

Evidence on the Preventive Effects of the Postbiotic Derived from Cow’s Milk Fermentation with Lacticaseibacillus paracasei CBA L74 against Pediatric Gastrointestinal Infections

“…The fermentation product is then pasteurized at 85 °C for 20 s for the inactivation of the living bacteria, and then spray dried. Thus, the final fermented milk powder contains only bacterial bodies and fermentation products, but not living microorganisms [ 11 , 12 , 13 , 14 , 15 , 16 ].…”

“…Intestinal epithelial cells employ a range of defense strategies to counteract RV invasion, including mucus production and cytokines/chemokines expression [ 18 ]. The potential protective action elicited by FM-CBAL74 against RV infection has been recently investigated in a validated model of human enterocytes [ 12 ]. It has been demonstrated that FM-CBAL74 was able to protect against gut barrier damage, characterized by cytoskeleton alterations and apoptosis, involving the ERK/JNK kinase pathway.…”

“…Furthermore, FM-CBAL74 was able to prevent RV-induced oxidative stress (ROS production) and pro-inflammatory cytokines (IL-8, IL-6, and TNF-α) release, suggesting a potent inhibition of gut inflammation. These results suggest that the postbiotic FM-CBAL74 could be a disrupting nutritional strategy against RV-induced AGE ( Figure 5 A) [ 12 ]. The gastrointestinal tract is a target organ for SARS-CoV-2, the single-stranded RNA virus that is the agent of Coronavirus disease (COVID-19).…”

“… Protective action of FM-CBAL74 against viral infections in human enterocytes . ( Panel A ): FM-CBAL74 elicited beneficial effects on the gut barrier integrity preventing an RV-induced decrease in transepithelial electrical resistance and up-regulating the tight junction protein occludin, and reducing the RV-induced increase in IL-8 and TNF-α production in Caco-2 cells [ 12 ]. ( Panel B ): FM-CBAL74 was able to significantly reduce the number of infected enterocytes, as demonstrated by the reduction of nucleocapsid viral protein (N) positive cells, and to down-regulated ACE2 expression, preventing SARS-CoV-2 entry into human enterocytes.…”