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Helicobacter pylori, the most frequent pathogens worldwide that colonize around 50% of the world’s population,
cause important diseases such as gastric adenocarcinoma, chronic gastritis, and gastric mucosa-associated lymphoid tissue
(MALT) lymphoma. In recent years, various studies have reported that H. pylori biofilm may be one of the critical barriers to
the eradication of this bacterial infection. Biofilms inhibit the penetration of antibiotics, increase the expression of efflux
pumps and mutations, multiple therapeutic failures, and chronic infections. Nanoparticles and natural products can demolish
H. pylori biofilm by destroying the outer layers and inhibiting the initial binding of bacteria. Also, the use of combination
therapies destroying extracellular polymeric substances decreases coccoid forms of bacteria and degrading polysaccharides in
the outer matrix that lead to an increase in the permeability and performance of antibiotics. Different probiotics, antimicrobial
peptides, chemical substances, and polysaccharides by inhibiting adhesion and colonization of H. pylori can prevent biofilm
formation by this bacterium. Of note, many of the above are applicable to acidic pH and can be used to treat gastritis. Therefore, H. pylori biofilm may be one of the major causes of failure to the eradication of infections caused by this bacterium, and
antibiotics are not capable of destroying the biofilm. Thus, it is necessary to use new strategies to prevent recurrent and chronic
infections by inhibiting biofilm formation.