Integrated Transcriptomic and Proteomic Analyses Revealed the Mechanism of the Osmotic Stress Response in Lacticaseibacillus rhamnosus ATCC 53103

<i>Lacticaseibacillus rhamnosus</i> (<i>Lbs. rhamnosus</i>) is renowned for its tolerance to gastric acid and adaptability to bile and alkaline conditions, and is crucial for intestinal health and immune regulation. In this study, integrated transcriptomic and proteomic analyses were employed to elucidate the response mechanisms of <i>Lbs. rhamnosus</i> under osmotic stress, induced by exposure to 0.6 M sodium lactate, which elevates environmental osmotic pressure. It was shown that 792 differentially expressed genes and 138 differentially expressed proteins were detected in <i>Lbs. rhamnosus</i> ATCC 53103 treated with osmotic stress. The differential regulation of these genes/proteins mainly includes the inhibition of fatty acid metabolism with membrane structural remodeling (downregulation of the acetyl coenzyme A carboxylase family and fatty acid binding protein family expression), dynamic homeostasis of amino acid metabolism (restriction of the synthesis of histidine, cysteine, leucine, etc., and enhancement of the catabolism of lysine, tryptophan, etc.), and survival-oriented reconfiguration of carbohydrate metabolism (gene expression related to the glycolytic pathway increases, while gene expression related to the pentose phosphate pathway decreases). These synergistic alterations in metabolic regulation may facilitate the adaptive response of <i>Lbs. rhamnosus</i> ATCC 53103 to osmotic stress. Overall, our findings deepen the current understanding of the stress response mechanisms in lactic acid bacteria and offer novel insights into the survival strategies employed by <i>Lbs. rhamnosus</i> ATCC 53103 under hyperosmotic conditions.