Daidzein-betaine cocrystal alleviates high-energy and low-protein diet induced fatty liver hemorrhagic syndrome in laying hens through gut-liver axis.

Fatty liver hemorrhagic syndrome (FLHS) severely endangers the health and productivity of laying hens, marked by hepatic steatosis and impaired lipid metabolism. Daidzein-betaine cocrystal improves lipid metabolism in the diet-induced obesity mice. We investigated the effects of daidzein-betaine cocrystal diet on production performance, egg quality, intestinal injury, cecal microbiota, the metabolites of intestinal microbiota and hepatic lipid metabolism in FLHS laying hens. A total of 108 twenty-eight-week-old laying hens were allocated to 6 treatments: the control group (normal diet), model group (high-energy and low-protein (HELP) diet), daidzein group (200 mg/kg daidzein + HELP diet), betaine group (184.62 mg/kg betaine + HELP diet), physical mixture group (384.62 mg/kg physical mixture + HELP diet) and daidzein-betaine cocrystal group (384.62 mg/kg daidzein-betaine cocrystal + HELP diet). The findings showed that intake of daidzein, betaine, physical mixture and daidzein-betaine cocrystal effectively alleviated the disordered lipid metabolism in laying hens fed a HELP diet. Moreover, daidzein-betaine cocrystal was best supplement in the improvement of the lipid metabolism. The daidzein-betaine cocrystal modulated the dysbiosis induced by HELP-diet through reducing the abundance of Desulfovibrio and increasing the abundance of Rikenellaceae_RC9_gut_group and Unclassified_f_Lachnospiraceae, whereas enhancing β-diversity of the gut microbiome, to restore equilibrium. Fecal metabolomics analysis showed that the indicators related to the 6 differentially abundant metabolites (DAMs) of lipid metabolism were improved. Transcriptome analysis identified 12 differentially expressed genes (DEGs) related to lipid metabolism. DAMs and DEGs were mainly co-enriched in peroxisome proliferators-activated receptor (PPAR) signaling pathways. To sum up, our results showed that dietary daidzein-betaine cocrystal could alleviate hepatic metabolic disorders associated with FLHS in laying hens by regulating the "gut-liver axis". This highlights the significant potential of the daidzein-betaine cocrystal as a therapeutic agent for counteracting the impacts of a HELP diet.