Gallstone Disease and Microbiome
Authors: Irina N Grigor&#x27;eva
Tatyana I Romanova
Journal: Microorganisms (2020)
Discipline: MICROBIOLOGY
Keywords: bile acids; bile ducts; cholecystectomy; gallstone disease; gut
Affiliations: Laboratory of Gastroenterology, Research Institute of Internal and Preventive Medicine-Branch of The Federal Research Center Institute of Cytology and Genetics of Siberian Branch of Russian Academy of Sciences, Novosibirsk 630089, Russia.

Abstract:  Gallstone disease (GSD) has, for many years, remained a high-cost, socially significant public health problem. Over the past decade, a number of studies have been carried out-both in humans and in animal models-confirming the role of the microbiota in various sections of the gastrointestinal tract as a new link in the etiopathogenesis of GSD. The microbiome of bile correlates with the bacterial composition of saliva, and the microbiome of the biliary tract has a high similarity with the microbiota of the duodenum. Pathogenic microflora of the oral cavity, through mechanisms of immunomodulation, can affect the motility of the gallbladder and the expression of mucin genes (MUC1, Muc3, MUC4), and represent one of the promoters of stone formation in the gallbladder. The presence of H. pylori infection contributes to the formation of gallstones and affects the occurrence of complications of GSD, including acute and chronic cholecystitis, cholangitis, pancreatitis. Intestinal bacteria (Clostridium, Bifidobacterium, Peptostreptococcus, Bacteroides, Eubacterium, and Escherichia coli) participating in the oxidation and epimerization of bile acids can disrupt enterohepatic circulation and lead to the formation of gallstones. At the same time, cholecystectomy due to GSD leads to the further transformation of the composition of the microbiota in various parts of the gastrointestinal tract, increasing the risk of developing stomach cancer and colorectal cancer. Further research is required to determine the possibility of using the evaluation of the composition of the microbiota of the gastrointestinal and biliary tracts as an early diagnostic marker of various gastroenterological diseases. 

Retracted: No

PubPeer comments:
 First of all, I cannot help but noting that the authors had an apparently peculiar way of providing references for their statements. Let me give some examples from the Introduction. The authors wrote that u201cLater, in several works, it was demonstrated that changes in the gut microbiota are also one of the etiological factors of cholesterol gallstonesu201d , citing Yoon,W.J.; Kim, H.N.; Park, E.; Ryu, S.; Chang, Y.; Shin, H.; Kim, H.L.; Yi, S.Y. The Impact of Cholecystectomy on the Gut Microbiota: A Case-Control Study. J. Clin. Med. 2019, 8, 79. But, if or when one turns to this article, one shall find that the authors are very far from concluding that gut microbiota is one of the key etiological factors of gallstones, concluding that u201cu2026there was little difference in the diversity of the gut microbiota between the cholecystectomy and control groupsu201d and stating, in respect to the increased abundance of B. obeum and V. parvula, in the CCE group, that u201cThe impact of such changes in the gut microbiota on health remains to be determinedu201d. Besides, Yoon et al. (2019) did not specify the time span elapsed from the CCE to fecal (not gut, strictly speaking!), so readers conclude that it might have been different among the CCE subjects, which makes it a serious methodological flaw in the study, that should have been addresses by the authors. The authors wrote that u201cThe main factors contributing to the formation of gallstones are defective gallbladder motility, metabolism and secretion of cholesterol and bile acidsu201d, supporting the statement by citing the study by Wu, T., Zhang, Z., Liu, B., et al. (2013). Gut microbiota dysbiosis and bacterial community assembly associated with cholesterol gallstones in large-scale study. BMC genomics, 14, 669. https: doi.org 10.1186 1471-2164-14-669. However, the study is solely devoted to the microbiome in gallstone disease patients, and its main conclusion is that the presence of u201cgut microbiota dysbiosis among gallstone patientsu2026 may be a key contributor to the complex bacteria community assembly linked with the presence of cholesterol gallstonesu201d, saying nothing about gallbladder motility etc. The authors stated that u201cThere is currently an increasing number of studies about the role of the gut microbiome as a key link in the pathogenesis of GSDu201d, citing in support the work (Di Ciaula, A., Portincasa, P. (2018). Recent advances in understanding and managing cholesterol gallstones. F1000Research, 7, F1000 Faculty Rev-1529. https: doi.org 10.12688 f1000research.15505.1). But that article is a review, that did not mention u201cmicrobiomeu201d AT ALL, let alone its key involvement in gallstone formation. Instead they use the term u201cmicrobiotau201d, but also far from regarding it u201cthe key linku201d, using mostly the tentative phrases, like u201cThe potential effects of the intestinal microbiota on the pathogenesis of cholesterol gallstones should not be neglectedu201d, or speaking about mouse modelsu201d. The authors stated that u201cDisorders of bile acid metabolism are the leading factors in the pathogenesis of cholesterol GSDu201d, supporting the statement by the reference Wang, T.Y.; Portincasa, P.; Liu, M.; Tso, P.; Wang, D.Q.-H. Mouse models of gallstone disease. Curr. Opin.Gastroenterol. 2018, 34, 59u201370, and nothing pertaining to humans! As the number of publications referenced in the study totals 134, I have no time to review all of them for correctness of the context in which they were cited. However, by now I dare say that I am fully aware about the referencing methodology employed by the authors. There are also some incorrect terms, e.g. type (in taxonomical sense) instead of phylum. In addition to all of the above, the authors, both from Russian Federation, and allegedly specialists in this specific field of gallstone disease (GSD), did not give the number of the cholecystectomies (CCE) performed in their country, which is definitely of great interest to international readers. Instead, they provided the CCE rate for the USA (the number widely known and jumping from review to review) or GSD prevalence in Germany. But Conclusions section produces especially intriguing impression by the very first sentence with the wordsu201du2026considering the contribution of changes in the specific microbial metabolic activity regarding the composition of bileu2026u201d as practically no reviewing of such specific microbial metabolic activity was performed throughout the text, besides few correlations between microbiome composition (not activity!) and GDS. ,