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Indole-3-lactic acid (ILA) has exhibited antimicrobial properties. However, its role in inhibiting Helicobacter pyloriinfection remains elusive. This study investigated the inhibitory effect of ILA produced by Lacticaseibacillus paracaseion H. pylori, which was further confirmed by cell and animal experiments. 5 mg/mL ILA was sufficient to directly inhibit the growth of H. pyloriin vitro, with a urease inhibitory activity reaching 60.94 ± 1.03%, and the cell morphology and structure were destroyed. ILA inhibited 56.5% adhesion of H. pylorito GES-1 and significantly reduced the number of apoptotic cells. Furthermore, ILA suppresses H. pyloricolonization by approximately 38% to 63%, reduced inflammation and oxidative stress in H. pylori-infected mice, and enhanced the enrichment and variety of gut microbiota, notably fostering the growth of beneficial bacteria such as Lactobacillusand Bifidobacteriumstrains. The results support that ILA derived from Lactobacilluscan be applicated as a novel prebiotic in anti-H. pylorifunctional foods.

This study aimed to elucidate the molecular mechanism of Lactiplantibacillus plantarumNMGL2 (L. plantarumNMGL2) isolated from traditional Inner Mongolia cheese that how it survived under simultaneous cold and acid conditions, and developed potential protective strategies for bacterial survivability. L. plantarumNMGL2 was previously shown with numerous bioactivities such as antibiofilm, cholesterol-lowering effect, and bile acids binding capacity. In this study, non-directional UPLC-Q-TOF-MS/MS-based metabolomics was performed to investigate the metabolic variations in L. plantarumNMGL2 during refrigerated storage of the fermented milk to comprehend the underlying chemical process of bacterial resistance under the cold and acid conditions. Organic acids, fatty acids, polypeptides, amino acids, and carbohydrates were all among the 122 differently abundant metabolites discovered, which were mostly involved in organic acid, sugar, protein, amino acid, and purine metabolisms, This indicated that the bacteria counteracted the combinational coldness and acidity by increased biosynthesis of several important biomolecules such as glycolipids and glycoproteins for providing cell protection, glutamate for initiating cell deacidification process, and DNA for cell repairing, as well as cell membrane proteins and cell wall peptidoglycan. Western blot analysis confirmed up-regulation of PGRP protein, implicating that the cell wall peptidoglycan played a significant part in bacterial resistance under cold and acid conditions. Further SPME-GC/MS analysis demonstrated different volatile metabolites detected in the fermented milk during the storage, including 7 acids, 4 alcohols, 2 aldehydes, 4 ketones and 3 esters, which provided unique flavor characteristic of fermented milk for favorable consumer acceptance of the product. For the first time, our research elucidates the molecular mechanism by which L. plantarumsurvives simultaneous cold and acid conditions with development of potential protective strategies under such conditions.