perinatologyРоссийский вестник перинатологии и педиатрииRossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics)1027-40652500-2228Ltd. “The National Academy of Pediatric Science and Innovation”10.21508/1027-4065-2023-68-3-46-54perinatology-1825Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESВлияние урсодезоксихолевой кислоты на кишечную микробиоту у детей с хроническими заболеваниями печениEffect of ursodeoxycholic acid on the intestinal microbiota in children with chronic liver diseasehttps://orcid.org/0000-0002-5413-9599ВолынецГ. В.VolynetsG. V.

Волынец Галина Васильевна - д.м.н., гл. науч. сотр., рук. отдела гастроэнтерологии

125412 Москва, ул. Талдомская, д. 2

Moscow

volynec_g@mail.ruhttps://orcid.org/0000-0001-8837-9243НикитинА. В.NikitinA. V.

Никитин Артем Вячеславович - к.м.н., вед. науч. сотр. отдела гастроэнтерологии; асс. кафедры гастроэнтерологии факультета дополнительного профессионального образования

125412 Москва, ул. Талдомская, д. 2

Moscow

https://orcid.org/0000-0002-6525-8665СкворцоваТ. А.SkvortsovaT. A.

Скворцова Тамара Андреевна - к.м.н., вед. науч. сотр. отдела гастроэнтерологии; доц. кафедры 2 гастроэнтерологии факультета дополнительного профессионального образования; зав. отделением гастроэнтерологии

125412 Москва, ул. Талдомская, д. 2

Moscow

https://orcid.org/0000-0003-4905-2373ПотаповА. С.PotapovA. S.

Потапов Александр Сергеевич - д.м.н., проф., гл. науч. сотр., зав. гастроэнтерологическим отделением с гепатологической группой; профессор кафедры педиатрии и детской ревматологии

119296 Москва, Ломоносовский проспект, д. 2, стр. 1

Moscow

https://orcid.org/0000-0002-6271-5218ДудуричВ. В.DudurichV. V.

Дудурич Василиса Валерьевна - рук. отдела «Микробиом» лаборатории

199106 Санкт-Петербург, Большой проспект Васильевского острова, д. 90, корп. 2

St. Petersburg

https://orcid.org/0000-0002-4479-3095ДаниловЛ. Г.DanilovL. G.

Данилов Лаврентий Глебович - биоинформатик лаборатории

199106 Санкт-Петербург, Большой проспект Васильевского острова, д. 90, корп. 2

St. Petersburg

ОСП «Научно-исследовательский клинический институт педиатрии и детской хирургии им. академика Ю.Е. Вельтищева» (Институт Вельтищева) ФГАОУ ВО РНИМУ им. Н.И. Пирогова Минздрава РоссииРоссияVeltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery of the Pirogov Russian National Research Medical UniversityRussian FederationОСП «Научно-исследовательский клинический институт педиатрии и детской хирургии им. академика Ю.Е. Вельтищева» (Институт Вельтищева) ФГАОУ ВО РНИМУ им. Н.И. Пирогова Минздрава России; ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава РоссииРоссияVeltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery of the Pirogov Russian National Research Medical University; Pirogov Russian National Research Medical UniversityRussian FederationОСП «Научно-исследовательский клинический институт педиатрии и детской хирургии им. академика Ю.Е. Вельтищева» (Институт Вельтищева) ФГАОУ ВО РНИМУ им. Н.И. Пирогова Минздрава России; ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России; ГБУЗ «Морозовская детская городская клиническая больница ДЗМ»РоссияVeltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery of the Pirogov Russian National Research Medical University; Pirogov Russian National Research Medical University; Morozov Children’s Municipal Clinical HospitalRussian FederationФГАУ «Национальный медицинский исследовательский центр здоровья детей» Минздрава РоссииРоссияNational Medical Research Center for Children’s HealthRussian FederationМедико-генетический центр CERBALABРоссияMedical Genetic Center «CERBALAB»Russian FederationМедико-генетический центр CERBALAB; ФГБОУ ВО «Санкт-Петербургский государственный университет»РоссияMedical Genetic Center «CERBALAB»; Saint Petersburg State UniversityRussian Federation2023150720236834654Copyright © Ltd. “The National Academy of Pediatric Science and Innovation”, 20232023Ltd. “The National Academy of Pediatric Science and Innovation”Ltd. “The National Academy of Pediatric Science and Innovation”https://www.ped-perinatology.ru/jour/about/submissions#copyrightNoticehttps://www.ped-perinatology.ru/jour/article/view/1825

Урсодезоксихолевая кислота представляет собой третичную желчную кислоту, у человека она содержится в низкой концентрации, обладает хорошо известными терапевтическими свойствами и первоначально использовалась для лечения холестатических заболеваний печени. Однако исследований по влиянию урсодезоксихолевой кислоты на состав кишечной микробиоты очень мало, особенно у детей с хроническими заболеваниями печени.Цель исследования. Определить различия в таксономическом разнообразии микробиоты кала у детей с хроническими заболеваниями печени, которые получают или не получают урсодезоксихолевую кислоту.Материал и методы. Проведен метагеномный анализ кишечной микробиоты у 24 детей с хроническими заболеваниями печени (средний возраст 10,3±4,7 года) с выделением региона V3–V4 гена 16S рРНК. В исследуемую группу вошли 18 детей с аутоиммунными заболеваниями печени и 6 детей с неаутоиммунными заболеваниями печени. В основную группу вошли 17 детей, которые получали урсодезоксихолевую кислоту. Группу сравнения составили 7 детей, не получавшие урсодезоксихолевую кислоту.Результаты. Выявлено, что образцы кала, полученные у пациентов, получающих препараты урсодезоксихолевой кислоты, не отличаются по таксономическому разнообразию кишечной микробиоты от образцов пациентов, не получающих этот препарат. Более детальное исследование по определению таксономического разнообразия в образцах пациентов, получающих урсодезоксихолевую кислоту, и детей, не получающих препараты урсодезоксихолевой кислоты, с использованием метода sPLS-DA, показало, что у пациентов, не получающих препараты урсодезоксихолевой кислоты, доминируют такие таксоны, как Streptococcus anginosus, Coprococcus eutactus, Desulfovibrio desulfuricans, Angelakisella massiliensis и Gemella haemolysans. При этом для пациентов, получающих препараты урсодезоксихолевой кислоты, характерно доминирование таксона Anaerostipes hadrus. Анализ различий процентного соотношения видов бактерий кишечной микробиоты показал, что у пациентов, получающих урсодезоксихолевую кислоту, повышена концентрация A. hadrus, в то время как у пациентов, не получающих эти препараты, значительно увеличено содержание Bacteroides dorei, Akkermansia muciniphila, а также увеличено количество других бактерий.Заключение. Урсодезоксихолевая кислота положительно влияет на кишечную микробиоту у детей с хроническими заболеваниями печени, увеличивая количество микроорганизмов, вырабатывающих короткоцепочечные жирные кислоты.

Ursodeoxycholic acid is a secondary bile acid (BA), present in humans at low concentrations, with well-known therapeutic properties, and was originally used to treat cholestatic liver disease. However, there are very few studies on the effect of ursodeoxycholic acid on the composition of the gut microbiota, especially in children with chronic liver diseases.Purpose. To determine differences in the taxonomic diversity of the fecal microbiota in children with chronic liver disease who receive or do not receive ursodeoxycholic acid.Material and methods. A metagenomic analysis of the intestinal microbiota of 24 children with chronic liver diseases (mean age 10.3 ± 4.7 years) was carried out with the identification of the V3–V4 region of the 16S rRNA gene. The group included 18 children with autoimmune liver diseases and 6 children with non-autoimmune liver diseases. 17 children received ursodeoxycholic acid. The comparison group consisted of 7 children who did not receive ursodeoxycholic acid.Results. This study found that fecal samples from patients treated with ursodeoxycholic acid do not differ in the taxonomic diversity of the gut microbiota from samples from patients not treated with ursodeoxycholic acid. A more detailed study to determine the existing taxonomic diversity in samples of patients treated with ursodeoxycholic acid and not treated with ursodeoxycholic acid, using the sPLS-DA method, showed that taxa such as Streptococcus anginosus, Coprococcus eutactus, Desulfovibrio desulfuricans, Angelakisella massiliensis and Gemella haemolysans dominated in patients not treated with ursodeoxycholic acid. And for patients receiving drugs with ursodeoxycholic acid, the dominance of the taxon Anaerostipes hadrus is typical. An analysis of differences in the percentage of intestinal microbiota bacterial species showed that patients receiving ursodeoxycholic acid had a higher count of Anaerostipes hadrus, while in patients not receiving ursodeoxycholic acid preparations, the count of Bacteroides dorei, Akkermansia muciniphila was significantly increased, and the counts of other bacteria were also increased.Conclusion. Studies have shown that ursodeoxycholic acid has a positive effect on the intestinal microbiota in children with chronic liver disease by increasing the number of microorganisms that produce short-chain fatty acids.

детикишечная микробиотахронические болезни печениурсодезоксихолевая кислотасhildrengut microbiotachronic liver diseasesursodeoxycholic acidReferencesSong X., Sun X., Oh S.F., Wu M., Zhang Y., Zheng W. et al. Microbial bile acid metabolites modulate gut RORγ regulatory T cell homeostasis. Nature 2020; 577(7790): 410–415. DOI: 10.1038/s41586–019–1865–0Song X., Sun X., Oh S.F., Wu M., Zhang Y., Zheng W. et al. Microbial bile acid metabolites modulate gut RORγ regulatory T cell homeostasis. Nature 2020; 577(7790): 410–415. DOI: 10.1038/s41586–019–1865–0Jia W., Xie G., Jia W. Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis. Nat Rev Gastroenterol Hepatol 2018; 15(2): 111–128. DOI: 10.1038/nrgastro.2017.119Jia W., Xie G., Jia W. Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis. Nat Rev Gastroenterol Hepatol 2018; 15(2): 111–128. DOI: 10.1038/nrgastro.2017.119Jones R.M., Neish A.S. Gut Microbiota in Intestinal and Liver Disease. Annu Rev Pathol 2021; 16: 251–275. DOI: 10.1146/annurev-pathol-030320–095722Jones R.M., Neish A.S. Gut Microbiota in Intestinal and Liver Disease. Annu Rev Pathol 2021; 16: 251–275. DOI: 10.1146/annurev-pathol-030320–095722Yang M., Gu Y., Li L., Liu T., Song X., Sun Y. et al. Bile Acid-Gut Microbiota Axis in Inflammatory Bowel Disease: From Bench to Bedside. Nutrients 2021; 13(9): 3143. DOI: 10.3390/nu13093143Yang M., Gu Y., Li L., Liu T., Song X., Sun Y. et al. Bile Acid-Gut Microbiota Axis in Inflammatory Bowel Disease: From Bench to Bedside. Nutrients 2021; 13(9): 3143. DOI: 10.3390/nu13093143Chen M.L., Takeda K., Sundrud M.S. Emerging roles of bile acids in mucosal immunity and inflammation. Mucosal Immunol 2019; 12(4): 851–861. DOI: 10.1038/s41385–019–0162–4Chen M.L., Takeda K., Sundrud M.S. Emerging roles of bile acids in mucosal immunity and inflammation. Mucosal Immunol 2019; 12(4): 851–861. DOI: 10.1038/s41385–019–0162–4Song Z., Cai Y., Lao X., Wang X., Lin X., Cui Y. et al. Taxonomic profiling and populational patterns of bacterial bile salt hydrolase (BSH) genes based on worldwide human gut microbiome. Microbiome 2019; 7(1): 9. DOI: 10.1186/s40168–019–0628–3Song Z., Cai Y., Lao X., Wang X., Lin X., Cui Y. et al. Taxonomic profiling and populational patterns of bacterial bile salt hydrolase (BSH) genes based on worldwide human gut microbiome. Microbiome 2019; 7(1): 9. DOI: 10.1186/s40168–019–0628–3Gérard P. Metabolism of cholesterol and bile acids by the gut microbiota. Pathogens. 2013; 3(1): 14–24. DOI: 10.3390/pathogens3010014Gérard P. Metabolism of cholesterol and bile acids by the gut microbiota. Pathogens. 2013; 3(1): 14–24. DOI: 10.3390/pathogens3010014Wahlström A., Sayin S.I., Marschall H.U., Bäckhed F. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metab 2016; 24(1): 41–50. DOI: 10.1016/j.cmet.2016.05.005Wahlström A., Sayin S.I., Marschall H.U., Bäckhed F. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metab 2016; 24(1): 41–50. DOI: 10.1016/j.cmet.2016.05.005Xiao L., Pan G. An important intestinal transporter that regulates the enterohepatic circulation of bile acids and cholesterol homeostasis: the apical sodium-dependent bile acid transporter (SLC10A2/ASBT). Clin Res Hepatol Gastroenterol 2017; 41(5): 509–515. DOI: 10.1016/j.clinre.2017.02.001Xiao L., Pan G. An important intestinal transporter that regulates the enterohepatic circulation of bile acids and cholesterol homeostasis: the apical sodium-dependent bile acid transporter (SLC10A2/ASBT). Clin Res Hepatol Gastroenterol 2017; 41(5): 509–515. DOI: 10.1016/j.clinre.2017.02.001Sayin S.I., Wahlström A., Felin J., Jäntti S., Marschall H.U., Bamberg K. et al. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab 2013; 17(2): 225–235. DOI: 10.1016/j.cmet.2013.01.003Sayin S.I., Wahlström A., Felin J., Jäntti S., Marschall H.U., Bamberg K. et al. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab 2013; 17(2): 225–235. DOI: 10.1016/j.cmet.2013.01.003Ilan Y. Leaky gut and the liver: a role for bacterial translocation in nonalcoholic steatohepatitis. World J Gastroenterol 2012; 18(21): 2609–2618. DOI: 10.3748/wjg.v18.i21.2609Ilan Y. Leaky gut and the liver: a role for bacterial translocation in nonalcoholic steatohepatitis. World J Gastroenterol 2012; 18(21): 2609–2618. DOI: 10.3748/wjg.v18.i21.2609Fouts D.E., Torralba M., Nelson K.E., Brenner D.A., Schnabl B. Bacterial translocation and changes in the intestinal microbiome in mouse models of liver disease. J Hepatol 2012; 56(6): 1283–1292. DOI: 10.1016/j.jhep.2012.01.019Fouts D.E., Torralba M., Nelson K.E., Brenner D.A., Schnabl B. Bacterial translocation and changes in the intestinal microbiome in mouse models of liver disease. J Hepatol 2012; 56(6): 1283–1292. DOI: 10.1016/j.jhep.2012.01.019Hackstein C.P., Assmus L.M., Welz M., Klein S., Schwandt T., Schultze J. et al. Gut microbial translocation corrupts myeloid cell function to control bacterial infection during liver cirrhosis. Gut 2017; 66(3): 507–518. DOI: 10.1136/gutjnl-2015–311224Hackstein C.P., Assmus L.M., Welz M., Klein S., Schwandt T., Schultze J. et al. Gut microbial translocation corrupts myeloid cell function to control bacterial infection during liver cirrhosis. Gut 2017; 66(3): 507–518. DOI: 10.1136/gutjnl-2015–311224Hartmann P., Haimerl M., Mazagova M., Brenner D.A., Schnabl B. Toll-like receptor 2-mediated intestinal injury and enteric tumor necrosis factor receptor I contribute to liver fibrosis in mice. Gastroenterology 2012; 143(5): 1330–1340.e1. DOI: 10.1053/j.gastro.2012.07.099Hartmann P., Haimerl M., Mazagova M., Brenner D.A., Schnabl B. Toll-like receptor 2-mediated intestinal injury and enteric tumor necrosis factor receptor I contribute to liver fibrosis in mice. Gastroenterology 2012; 143(5): 1330–1340.e1. DOI: 10.1053/j.gastro.2012.07.099Corpechot C. Primary biliary cirrhosis and bile acids. Clin Res Hepatol Gastroenterol 2012; 36 Suppl 1: S13–20. DOI: 10.1016/S2210–7401(12)70016–5Corpechot C. Primary biliary cirrhosis and bile acids. Clin Res Hepatol Gastroenterol 2012; 36 Suppl 1: S13–20. DOI: 10.1016/S2210–7401(12)70016–5Sannasiddappa T.H., Lund P.A., Clarke S.R. In Vitro Antibacterial Activity of Unconjugated and Conjugated Bile Salts on Staphylococcus aureus. Front Microbiol 2017;8:1581. DOI: 10.3389/fmicb.2017.01581Sannasiddappa T.H., Lund P.A., Clarke S.R. In Vitro Antibacterial Activity of Unconjugated and Conjugated Bile Salts on Staphylococcus aureus. Front Microbiol 2017;8:1581. DOI: 10.3389/fmicb.2017.01581Watanabe M., Fukiya S., Yokota A. Comprehensive evaluation of the bactericidal activities of free bile acids in the large intestine of humans and rodents. J Lipid Res 2017; 58(6): 1143– 1152. DOI: 10.1194/jlr.M075143Watanabe M., Fukiya S., Yokota A. Comprehensive evaluation of the bactericidal activities of free bile acids in the large intestine of humans and rodents. J Lipid Res 2017; 58(6): 1143– 1152. DOI: 10.1194/jlr.M075143Tremblay S., Romain G., Roux M., Chen X.L., Brown K., Gibson D.L. et al. Bile acid administration elicits an intestinal antimicrobial program and reduces the bacterial burden in two mouse models of enteric infection. Infect Immun 2017; 85(6): e00942–16. DOI: 10.1128/IAI.00942–16Tremblay S., Romain G., Roux M., Chen X.L., Brown K., Gibson D.L. et al. Bile acid administration elicits an intestinal antimicrobial program and reduces the bacterial burden in two mouse models of enteric infection. Infect Immun 2017; 85(6): e00942–16. DOI: 10.1128/IAI.00942–16Ding L., Yang L., Wang Z., Huang W. Bile acid nuclear receptor FXR and digestive system diseases. Acta Pharm Sin B 2015; 5(2): 135–144. DOI: 10.1016/j.apsb.2015.01.004Ding L., Yang L., Wang Z., Huang W. Bile acid nuclear receptor FXR and digestive system diseases. Acta Pharm Sin B 2015; 5(2): 135–144. DOI: 10.1016/j.apsb.2015.01.004Parséus A., Sommer N., Sommer F., Caesar R., Molinaro A., Ståhlman M. et al. Microbiota-induced obesity requires farnesoid X receptor. Gut 2017; 66(3): 429–437. DOI: 10.1136/gutjnl-2015–310283Parséus A., Sommer N., Sommer F., Caesar R., Molinaro A., Ståhlman M. et al. Microbiota-induced obesity requires farnesoid X receptor. Gut 2017; 66(3): 429–437. DOI: 10.1136/gutjnl-2015–310283Camilleri M. Bile Acid diarrhea: prevalence, pathogenesis, and therapy. Gut Liver. 2015; 9(3): 332–339. DOI: 10.5009/gnl14397Camilleri M. Bile Acid diarrhea: prevalence, pathogenesis, and therapy. Gut Liver. 2015; 9(3): 332–339. DOI: 10.5009/gnl14397Van den Bossche L., Hindryckx P., Devisscher L., Devriese S., Van Welden S., Holvoet T. et al. Ursodeoxycholic Acid and Its Taurine- or Glycine-Conjugated Species Reduce Colitogenic Dysbiosis and Equally Suppress Experimental Colitis in Mice. Appl Environ Microbiol 2017; 83(7): e02766–16. DOI: 10.1128/AEM.02766–16Van den Bossche L., Hindryckx P., Devisscher L., Devriese S., Van Welden S., Holvoet T. et al. Ursodeoxycholic Acid and Its Taurine- or Glycine-Conjugated Species Reduce Colitogenic Dysbiosis and Equally Suppress Experimental Colitis in Mice. Appl Environ Microbiol 2017; 83(7): e02766–16. DOI: 10.1128/AEM.02766–16Van den Bossche L., Borsboom D., Devriese S., Van Welden S., Holvoet T., Devisscher L. et al. Tauroursodeoxycholic acid protects bile acid homeostasis under inflammatory conditions and dampens Crohn’s disease-like ileitis. Lab Invest 2017; 97(5): 519–529. DOI: 10.1038/labinvest.2017.6Van den Bossche L., Borsboom D., Devriese S., Van Welden S., Holvoet T., Devisscher L. et al. Tauroursodeoxycholic acid protects bile acid homeostasis under inflammatory conditions and dampens Crohn’s disease-like ileitis. Lab Invest 2017; 97(5): 519–529. DOI: 10.1038/labinvest.2017.6Ward J.B.J., Lajczak N.K., Kelly O.B., O’Dwyer A.M., Giddam A.K., Ní Gabhann J. et al. Ursodeoxycholic acid and lithocholic acid exert anti-inflammatory actions in the colon. Am J Physiol Gastrointest Liver Physiol 2017; 312(6): G550–G558. DOI: 10.1152/ajpgi.00256.2016Ward J.B.J., Lajczak N.K., Kelly O.B., O’Dwyer A.M., Giddam A.K., Ní Gabhann J. et al. Ursodeoxycholic acid and lithocholic acid exert anti-inflammatory actions in the colon. Am J Physiol Gastrointest Liver Physiol 2017; 312(6): G550–G558. DOI: 10.1152/ajpgi.00256.2016Laukens D., Devisscher L., Van den Bossche L., Hindryckx P., Vandenbroucke R.E., Vandewynckel Y.P. et al. Tauroursodeoxycholic acid inhibits experimental colitis by preventing early intestinal epithelial cell death. Lab Invest 2014; 94(12): 1419–30. DOI: 10.1038/labinvest.2014.117Laukens D., Devisscher L., Van den Bossche L., Hindryckx P., Vandenbroucke R.E., Vandewynckel Y.P. et al. Tauroursodeoxycholic acid inhibits experimental colitis by preventing early intestinal epithelial cell death. Lab Invest 2014; 94(12): 1419–30. DOI: 10.1038/labinvest.2014.117Nadeem M.S., Kumar V., Al-Abbasi F.A., Kamal M.A., Anwar F. Risk of colorectal cancer in inflammatory bowel diseases. Semin Cancer Biol 2020; 64: 51–60. DOI: 10.1016/j.semcancer.2019.05.001Nadeem M.S., Kumar V., Al-Abbasi F.A., Kamal M.A., Anwar F. Risk of colorectal cancer in inflammatory bowel diseases. Semin Cancer Biol 2020; 64: 51–60. DOI: 10.1016/j.semcancer.2019.05.001Pearson T., Caporaso J.G., Yellowhair M., Bokulich N.A., Padi M., Roe D.J. et al. Effects of ursodeoxycholic acid on the gut microbiome and colorectal adenoma development. Cancer Med 2019; 8(2): 617–628. DOI: 10.1002/cam4.1965Pearson T., Caporaso J.G., Yellowhair M., Bokulich N.A., Padi M., Roe D.J. et al. Effects of ursodeoxycholic acid on the gut microbiome and colorectal adenoma development. Cancer Med 2019; 8(2): 617–628. DOI: 10.1002/cam4.1965Boonstra K., van Erpecum K.J., van Nieuwkerk K.M., Drenth J.P., Poen A.C., Witteman B.J. et al. Primary sclerosing cholangitis is associated with a distinct phenotype of inflammatory bowel disease. Inflamm Bowel Dis 2012; 18(12): 2270–2276. DOI: 10.1002/ibd.22938Boonstra K., van Erpecum K.J., van Nieuwkerk K.M., Drenth J.P., Poen A.C., Witteman B.J. et al. Primary sclerosing cholangitis is associated with a distinct phenotype of inflammatory bowel disease. Inflamm Bowel Dis 2012; 18(12): 2270–2276. DOI: 10.1002/ibd.22938Quraishi M.N., Acharjee A., Beggs A.D., Horniblow R., Tselepis C., Gkoutos G. et al. A Pilot Integrative Analysis of Colonic Gene Expression, Gut Microbiota, and Immune Infiltration in Primary Sclerosing Cholangitis-Inflammatory Bowel Disease: Association of Disease With Bile Acid Pathways. J Crohns Colitis 2020; 14(7): 935–947. DOI: 10.1093/ecco-jcc/jjaa021Quraishi M.N., Acharjee A., Beggs A.D., Horniblow R., Tselepis C., Gkoutos G. et al. A Pilot Integrative Analysis of Colonic Gene Expression, Gut Microbiota, and Immune Infiltration in Primary Sclerosing Cholangitis-Inflammatory Bowel Disease: Association of Disease With Bile Acid Pathways. J Crohns Colitis 2020; 14(7): 935–947. DOI: 10.1093/ecco-jcc/jjaa021Dyson J.K., Beuers U., Jones D.E.J., Lohse A.W., Hudson M. Primary sclerosing cholangitis. Lancet 2018; 391(10139): 2547–2559. DOI: 10.1016/S0140–6736(18)30300–3Dyson J.K., Beuers U., Jones D.E.J., Lohse A.W., Hudson M. Primary sclerosing cholangitis. Lancet 2018; 391(10139): 2547–2559. DOI: 10.1016/S0140–6736(18)30300–3Bowlus C.L., Arrivé L., Bergquist A., Deneau M., Forman L., Ilyas S.I. et al. AASLD practice guidance on primary sclerosing cholangitis and cholangiocarcinoma. Hepatology 2023; 77(2): 659–702. DOI: 10.1002/hep.32771Bowlus C.L., Arrivé L., Bergquist A., Deneau M., Forman L., Ilyas S.I. et al. AASLD practice guidance on primary sclerosing cholangitis and cholangiocarcinoma. Hepatology 2023; 77(2): 659–702. DOI: 10.1002/hep.32771Callahan B.J., McMurdie P.J., Rosen M.J., Han A.W., Johnson A.J., Holmes S.P. DADA2: High-resolution sample inference from Illumina amplicon data. Nat Methods 2016; 13(7): 581–583. DOI: 10.1038/nmeth.3869Callahan B.J., McMurdie P.J., Rosen M.J., Han A.W., Johnson A.J., Holmes S.P. DADA2: High-resolution sample inference from Illumina amplicon data. Nat Methods 2016; 13(7): 581–583. DOI: 10.1038/nmeth.3869Wang E.T., Moyzis R.K. Genetic evidence for ongoing balanced selection at human DNA repair genes ERCC8, FANCC, and RAD51C. Mutat Res 2007; 616(1–2): 165–174. DOI: 10.1016/j.mrfmmm.2006.11.030Wang E.T., Moyzis R.K. Genetic evidence for ongoing balanced selection at human DNA repair genes ERCC8, FANCC, and RAD51C. Mutat Res 2007; 616(1–2): 165–174. DOI: 10.1016/j.mrfmmm.2006.11.030Quast C., Pruesse E., Yilmaz P., Gerken J., Schweer T., Yarza P. et al. The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic Acids Res 2013; 41(Database issue): D590–596. DOI: 10.1093/nar/gks1219Quast C., Pruesse E., Yilmaz P., Gerken J., Schweer T., Yarza P. et al. The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic Acids Res 2013; 41(Database issue): D590–596. DOI: 10.1093/nar/gks1219Duboc H., Rajca S., Rainteau D., Benarous D., Maubert M.A., Quervain E. et al. Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases. Gut 2013; 62(4): 531–539. DOI: 10.1136/gutjnl-2012–302578Duboc H., Rajca S., Rainteau D., Benarous D., Maubert M.A., Quervain E. et al. Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases. Gut 2013; 62(4): 531–539. DOI: 10.1136/gutjnl-2012–302578Sinha S.R., Haileselassie Y., Nguyen L.P., Tropini C., Wang M., Becker L.S. et al. Dysbiosis-Induced Secondary Bile Acid Deficiency Promotes Intestinal Inflammation. Cell Host Microbe 2020; 27(4): 659–670.e5. DOI: 10.1016/j.chom.2020.01.021Sinha S.R., Haileselassie Y., Nguyen L.P., Tropini C., Wang M., Becker L.S. et al. Dysbiosis-Induced Secondary Bile Acid Deficiency Promotes Intestinal Inflammation. Cell Host Microbe 2020; 27(4): 659–670.e5. DOI: 10.1016/j.chom.2020.01.021Hang S., Paik D., Yao L., Kim E., Trinath J., Lu J. et al. Bile acid metabolites control TH17 and Treg cell differentiation. Nature. 2019; 576(7785): 143–148. DOI: 10.1038/s41586–019–1785-zHang S., Paik D., Yao L., Kim E., Trinath J., Lu J. et al. Bile acid metabolites control TH17 and Treg cell differentiation. Nature. 2019; 576(7785): 143–148. DOI: 10.1038/s41586–019–1785-zFiorucci S., Biagioli M., Zampella A., Distrutti E. Bile Acids Activated Receptors Regulate Innate Immunity. Front Immunol 2018; 9: 1853. DOI: 10.3389/fimmu.2018.01853Fiorucci S., Biagioli M., Zampella A., Distrutti E. Bile Acids Activated Receptors Regulate Innate Immunity. Front Immunol 2018; 9: 1853. DOI: 10.3389/fimmu.2018.01853Xu M., Shen Y., Cen M., Zhu Y., Cheng F., Tang L. et al. Modulation of the Gut Microbiota-farnesoid X Receptor Axis Improves Deoxycholic Acid-induced Intestinal Inflammation in Mice. J. J Crohns Colitis 2021; 15(7): 1197–1210. DOI: 10.1093/ecco-jcc/jjab003Xu M., Shen Y., Cen M., Zhu Y., Cheng F., Tang L. et al. Modulation of the Gut Microbiota-farnesoid X Receptor Axis Improves Deoxycholic Acid-induced Intestinal Inflammation in Mice. J. J Crohns Colitis 2021; 15(7): 1197–1210. DOI: 10.1093/ecco-jcc/jjab003Kant R., Rasinkangas P., Satokari R., Pietilä T.E., Palva A. Genome sequence of the butyrate-producing anaerobic bacterium Anaerostipes hadrus PEL 85. Genome Announc 2015; 3(2): e00224–15. DOI: 10.1128/genomeA.00224–15Kant R., Rasinkangas P., Satokari R., Pietilä T.E., Palva A. Genome sequence of the butyrate-producing anaerobic bacterium Anaerostipes hadrus PEL 85. Genome Announc 2015; 3(2): e00224–15. DOI: 10.1128/genomeA.00224–15Yoshida N., Emoto T., Yamashita T., Watanabe H., Hayashi T., Tabata T. et al. Bacteroides vulgatus and Bacteroides dorei Reduce Gut Microbial Lipopolysaccharide Production and Inhibit Atherosclerosis. Circulation 2018; 138(22): 2486–2498. DOI: 10.1161/CIRCULATIONAHA.118.033714Yoshida N., Emoto T., Yamashita T., Watanabe H., Hayashi T., Tabata T. et al. Bacteroides vulgatus and Bacteroides dorei Reduce Gut Microbial Lipopolysaccharide Production and Inhibit Atherosclerosis. Circulation 2018; 138(22): 2486–2498. DOI: 10.1161/CIRCULATIONAHA.118.033714Matsuoka T., Shimizu T., Minagawa T., Hiranuma W., Takeda M., Kakuta R. et al. First case of an invasive Bacteroides dorei infection detected in a patient with a mycotic aortic aneurysm-raising a rebellion of major indigenous bacteria in humans: a case report and review. BMC Infect Dis 2021; 21(1): 625. DOI: 10.1186/s12879–021–06345–8Matsuoka T., Shimizu T., Minagawa T., Hiranuma W., Takeda M., Kakuta R. et al. First case of an invasive Bacteroides dorei infection detected in a patient with a mycotic aortic aneurysm-raising a rebellion of major indigenous bacteria in humans: a case report and review. BMC Infect Dis 2021; 21(1): 625. DOI: 10.1186/s12879–021–06345–8Abuqwider J.N., Mauriello G., Altamimi M. Akkermansia muciniphila, a New Generation of Beneficial Microbiota in Modulating Obesity: A Systematic Review. Microorganisms 2021; 9(5): 1098. DOI: 10.3390/microorganisms9051098Abuqwider J.N., Mauriello G., Altamimi M. Akkermansia muciniphila, a New Generation of Beneficial Microbiota in Modulating Obesity: A Systematic Review. Microorganisms 2021; 9(5): 1098. DOI: 10.3390/microorganisms9051098

The authors declare that there are no conflicts of interest present.