**7. Enteric bacteria and gallbladder cancer**

Gallbladder cancer is the most common biliary tract cancer and the etiopathogenesis is multifactorial [86]. However, chronic inflammation [87] and gallstone disease represent the most important aetiologies in the development of GBC and are supported by Level II

evidence [88]. The recent development of culture and culture-independent techniques have identified various organisms which are associated with the formation of both pigmented as well as cholesterol gallstones [89, 90]. These dysbiotic organisms are mainly enteric bacteria that have the ability to form a biofilm, thereby resisting cellular and DNA damage caused by bile. They are namely, *E. coli*, *Pseudomonas aeruginosa*, *Klebsiella pneumoniae*, *Enterococcus spp*, *Acinetobacter spp* which were associated with the patients presenting with gallstones [91–93]. *Clostridium*, *Bifidobacterium*, *Peptostreptococcus*, *Bacteroides* were among the other bacteria leading to the formation of gallstones by interfering with the enterohepatic circulation [94, 95]. With the development of Polymerase chain reaction—denaturing gradient gel electrophoresis (PCR-DGGE), various uncultivable bacteria like *Staphylococcus hemolyticus*, *Enterobacter or Citrobacter spp*, *Morganella spp*, *Salmonella spp.*, *Capnocytophaga spp*, *Lactococcus species*, *Bacillus spp*, and *H. Pylori* have been isolated in different compositions [72, 96]. Some pathogens of the oral cavity have also been implicated in the formation of gallstones by affecting the motility of the gallbladder and the production of mucin [97]. These bacteria can be indirectly linked with GBC. Recent studies have demonstrated positive cultures of enteric bacteria in GBC patients projecting a direct association of the gut flora with GBC, however, the level of evidence is low [91].

Although various bacteria have now been identified and linked with the development of gallstones and their theoretical association with GBC, *Helicobacter species* and *Salmonella typhi* have been extensively studied and are strongly implicated in the development of GBC [98, 99].
