Effects of kefirs made from whole milk or whey on the pancreas-intestine axis in a mouse model of acute pancreatitis

Abstract

Background: acute pancreatitis (AP) is a severe inflammatory condition, often involving intestinal barrier dysfunction. Fermented foods like kefir, are potential therapeutic adjuvants due to their gut-modulatory properties. This study aimed to compare the protective effects of kefir made from pasteurized whole milk (PMK) or whey (WK) on pancreatic injury, intestinal barrier integrity, inflammation, and oxidative stress in a cerulein-induced mouse model of AP. Methods: male BALB/c mice were assigned to six groups: control, AP, PMK, WK, and AP combined with either PMK or WK. AP was induced by cerulein injections on days 10 and 11. Mice received kefir or saline via oral gavage for 14 days. Pancreatic and ileal tissues were analyzed for histopathological damage, serum amylase and lipase levels, gene expression of inflammatory and tight junction markers (TNF-α, IL-6, IL-1β, occludin, ZO-1), oxidative stress (MDA, carbonyls), and intestinal function. Results: AP induction was confirmed by elevated serum amylase/lipase and severe pancreatic damage. While both PMK and WK partially reduced pancreatic histopathological damage, they failed to reduce serum amylase and lipase levels. Furthermore, PMK, but not WK, partially attenuated pancreatic IL-6 and IL-1β expression, and both kefirs reduced ileal TNF-α. However, neither kefir prevented the AP-induced downregulation of tight junction genes, the increase in oxidative stress markers in either tissue, or the impairment of intestinal transit and contractility. Conclusion: kefir supplementation offers localized anti-inflammatory benefits in a severe AP model. It is insufficient to mitigate key systemic markers of pancreatic injury, restore gut barrier integrity, or reverse functional dysmotility. These findings suggest that the therapeutic potential of kefir may be limited in the context of severe acute inflammatory conditions.