{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T18:33:37Z","timestamp":1790102017382,"version":"4.0.1"},"reference-count":100,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    Proton pump inhibitors (PPIs) are among the most widely prescribed medications for gastric acid-related disorders. However, their effect on the gut microbiota remains incompletely understood, despite emerging evidence suggesting potential long-term alterations in microbial composition and reductions in beneficial taxa. In this study,\n                    <jats:italic>Lactobacillus acidophilus<\/jats:italic>\n                    , a well-known probiotic species, was used as a representative model organism to investigate the microbiological effects of PPIs. This specific bacterium is linked to immune modulation, vitamin metabolism, and the preservation of the epithelial barrier. The effects of PPIs on\n                    <jats:italic>L. acidophilus<\/jats:italic>\n                    at the structural and functional levels were elucidated by an integrated framework including subtractive genomics, molecular docking, molecular dynamics (MD) simulations, antimicrobial assays, and transcriptional analysis. Using a multi-criteria scoring system, essential, non-redundant, non-human homologous cytoplasmic proteins were ranked and mapped to important pathways such as ATP synthesis, peptidoglycan biosynthesis, amino-sugar metabolism, nucleotide metabolism, and protein maturation. Molecular docking suggested potential binding of pantoprazole and rabeprazole to targets such as MurA, MurB, MurE, GlmS, NadE, AtpD, Def, and PyrH proteins. MD simulation showed stable protein-PPI complexes with localized flexibility changes near catalytic domains while preserving the global fold. Consistent with\n                    <jats:italic>in-silico<\/jats:italic>\n                    expectations, both pantoprazole and rabeprazole exhibited dose-dependent growth inhibition of\n                    <jats:italic>L. acidophilus<\/jats:italic>\n                    , whereas qRT-PCR revealed transcriptional downregulation of genes involved in cell-wall production, NADH metabolism, and energy generation. Pantoprazole elicited the most uniform transcriptional suppression, whereas rabeprazole had stronger but more varied effects. The present findings provide preliminary insights into potential interactions between PPIs and probiotic bacteria at the molecular and cellular levels. However, the results reflect species-specific responses under\n                    <jats:italic>in vitro<\/jats:italic>\n                    conditions and should be interpreted cautiously, as transcriptional changes do not directly confirm functional inhibition and the concentrations tested may represent upper-range exposure scenarios. Further\n                    <jats:italic>in vivo<\/jats:italic>\n                    and multi-species studies are required to validate this observation and better understand their clinical implications for microbiome stability during PPI therapy.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2026.1781831","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:56:03Z","timestamp":1778219763000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Proton pump inhibitor exposure modulates functional and transcriptional responses in Lactobacillus acidophilus: a comprehensive computational and experimental insights"],"prefix":"10.3389","volume":"16","author":[{"given":"Romen Singh","family":"Naorem","sequence":"first","affiliation":[{"name":"Multidisciplinary Research Unit, Jorhat Medical College and Hospital","place":["Jorhat, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalpajit","family":"Dutta","sequence":"additional","affiliation":[{"name":"Multidisciplinary Research Unit, Jorhat Medical College and Hospital","place":["Jorhat, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudipta Sankar","family":"Bora","sequence":"additional","affiliation":[{"name":"Multidisciplinary Research Unit, Jorhat Medical College and Hospital","place":["Jorhat, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anju Barhai","family":"Teli","sequence":"additional","affiliation":[{"name":"Multidisciplinary Research Unit, Jorhat Medical College and Hospital","place":["Jorhat, India"]},{"name":"Department of Biochemistry, Jorhat Medical College and Hospital","place":["Jorhat, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers","volume":"1","author":"Abraham","year":"2015","journal-title":"Softwarex"},{"key":"B2","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1016\/j.ajpath.2021.02.003","article-title":"Lactobacillus acidophilus induces a strain-specific and toll-like receptor 2\u2013dependent enhancement of intestinal epithelial tight junction barrier and protection against intestinal inflammation","volume":"191","author":"Al-Sadi","year":"2021","journal-title":"Am. 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