Milk-derived extracellular vesicles protect intestinal barrier integrity in the gut-liver axis

Abstract

Milk-derived extracellular vesicles (mEVs) have been proposed as a potential nanomedicine for intestinal disorders; however, their impact on intestinal barrier integrity in gut inflammation and associated metabolic diseases has not been explored yet. Here, mEVs derived from bovine and human breast milk exert similar protective effects on epithelial tight junction functionality in vitro, survive harsh gastrointestinal conditions ex vivo, and reach the colon in vivo. Oral administration of mEVs restores gut barrier integrity at multiple levels, including mucus, epithelial, and immune barriers, and prevents endotoxin translocation into the liver in chemical-induced experimental colitis and diet-induced nonalcoholic steatohepatitis (NASH), thereby alleviating gut disorders, their associated liver inflammation, and NASH. Oral administration of mEVs has potential in the treatment of gut inflammation and gut-liver axis–associated metabolic diseases via protection of intestinal barrier integrity.

Neonatal enteroids absorb extracellular vesicles from human milk-fed infant digestive fluid

“…In vitro-simulated digestion studies suggest that EVs can survive low pH and the presence of some digestive enzymes (15, 24, 25), supporting our findings that some HMEVs can survive proximal gastrointestinal digestion. However, this does not account for the observed distinct reduction in HMEV abundance in the proximal intestine.…”

“…EVs, including human milk EVs (HMEVs), carry biological information between donor and recipient cells, to confer changes in cellular function or biological activity (14)(15)(16)(17)(18)(19)(20)(21)(22). HMEVs have putative beneficial effects, as shown by a combination of in vitro and animal studies demonstrating that HMEVs promote intestinal epithelial cell proliferation (16,19,20), reduce experimental necrotizing enterocolitis (NEC), limit inflammatory (15-17, 21, 22) or non-inflammatory damage (15,19,23), promote expression of intestinal barrier proteins (21), or enhance epithelial barrier function (15,18). Collectively, the data suggest that HMEVs confer functional benefits on intestinal epithelial cells (IECs) and hold immense therapeutic promise for humans.…”

“…Several in vitro studies indicate that HMEVs are minimally impacted by a pH of 4-4.5 mirroring that of a term or preterm infant stomach, as well as incubation with several gastrointestinal proteases (24)(25)(26). More recent work shows that bovine milk EVs are intact after exposure to a pH as low as 1.3 (15). Furthermore, existing animal studies indicate that bovine or murine milk-derived EVs survive murine digestion to reach the placenta and embryo (27) or intestine and brain (28,29).…”

Imaging Fibrosis Progression in NASH with an Allysine-Reactive AIE Probe

“…It can react with the aldehyde group on allylsine, the product of LOX, to turn on its fluorescence. Subsequently, we applied TPAH to monitor fibrosis along with NASH progression using methionine- and choline-deficient (MCD) diet-fed mice as the model. - Early-stage fibrosis was observed in MCD diet-fed mice from 8 weeks onward. Notably, the administration of an LOX inhibitor for two weeks significantly reduced the fibrosis, as evident by Picrosirius Red staining and in vivo fluorescence signal after TPAH injection, suggesting the role of LOX activity in fibrosis progression.…”

Dendrobium huoshanense Polysaccharide Improves High‐Fat Diet Induced Liver Injury by Regulating the Gut‐Liver Axis

“…NAFLD is characterized by dyslipidemia, insulin resistance, hepatic lipid deposition, liver inflammation, and abnormal liver function. Modern research has shown that the pathological development of NAFLD is strongly correlated with the gut‐liver axis [2,3] . The trillions of gut microorganisms not only assist for absorption of nutrients, but also are critical regulators of human and animal health.…”