The change in the gut microbiome and microbial metabolites in a patient suffering from severe and enduring anorexia nervosa (AN) and diagnosed with small intestinal bacterial overgrowth syndrome (SIBO) was investigated. Microbial gut dysbiosis is associated with both AN and SIBO, and therefore gut microbiome changes by serial fecal microbiota transplantation (FMT) is a possible therapeutic modality. This study assessed the effects of FMT on gut barrier function, microbiota composition, and the levels of bacterial metabolic products. The patient treatment with FMT led to the improvement of gut barrier function, which was altered prior to FMT. Very low bacterial alpha diversity, a lack of beneficial bacteria, together with a great abundance of fungal species were observed in the patient stool sample before FMT. After FMT, both bacterial species richness and gut microbiome evenness increased in the patient, while the fungal alpha diversity decreased. The total short-chain fatty acids (SCFAs) levels (molecules presenting an important source of energy for epithelial gut cells) gradually increased after FMT. Contrarily, one of the most abundant intestinal neurotransmitters, serotonin, tended to decrease throughout the observation period. Overall, gut microbial dysbiosis improvement after FMT was considered. However, there were no signs of patient clinical improvement. The need for an in-depth analysis of the donor´s stool and correct selection pre-FMT is evident.

Department of Internal Medicine 1st Faculty of Medicine Charles University and General University Hospital Prague Ke Karlovu 11 Prague 2 Czech Republic

Department of Psychiatry 1st Faculty of Medicine Charles University and General University Hospital Prague Ke Karlovu 11 Prague 2 Czech Republic

Faculty of Applied Sciences University of West Bohemia Univerzitni 8 306 14 Plzen Czech Republic

Faculty of Chemical Technology University of Chemistry and Technology Prague Technicka 5 166 28 Prague 6 Czech Republic

Laboratory of Cellular and Molecular Immunology Institute of Microbiology Academy of Sciences of the Czech Republic v v i 1083 Videnska Prague 4 Czech Republic

Laboratory of Molecular Structure Characterization Institute of Microbiology Academy of Sciences of the Czech Republic v v i 1083 Videnska Prague 4 Czech Republic

th Medical Department 1st Faculty of Medicine Charles University and General Faculty Hospital Prague U Nemocnice 2 128 08 Praha 2 Czech Republic

Zobrazit více v PubMed

Roubalova R., Prochazkova P., Papezova H., Smitka K., Bilej M., Tlaskalova-Hogenova H. Anorexia nervosa: Gut microbiota-immune-brain interactions. Clin. Nutr. 2019 doi: 10.1016/j.clnu.2019.03.023. PubMed DOI

Mendez-Figueroa V., Biscaia J.M., Mohedano R.B., Blanco-Fernandez A., Bailen M., Bressa C., Larrosa M., Gonzalez-Soltero R. Can Gut Microbiota and Lifestyle Help Us in the Handling of Anorexia Nervosa Patients? Microorganisms. 2019;7:58. doi: 10.3390/microorganisms7020058. PubMed DOI PMC

Sweeney T.E., Morton J.M. The human gut microbiome: a review of the effect of obesity and surgically induced weight loss. JAMA Surg. 2013;148:563–569. doi: 10.1001/jamasurg.2013.5. PubMed DOI PMC

Koliada A., Syzenko G., Moseiko V., Budovska L., Puchkov K., Perederiy V., Gavalko Y., Dorofeyev A., Romanenko M., Tkach S., et al. Association between body mass index and Firmicutes/Bacteroidetes ratio in an adult Ukrainian population. BMC Microbiol. 2017;17:120. doi: 10.1186/s12866-017-1027-1. PubMed DOI PMC

Collado M.C., Derrien M., Isolauri E., de Vos W.M., Salminen S. Intestinal integrity and Akkermansia muciniphila, a mucin-degrading member of the intestinal microbiota present in infants, adults, and the elderly. Appl. Environ. Microbiol. 2007;73:7767–7770. doi: 10.1128/AEM.01477-07. PubMed DOI PMC

Cani P.D., de Vos W.M. Next-Generation Beneficial Microbes: The Case of Akkermansia muciniphila. Front. Microbiol. 2017;8:1765. doi: 10.3389/fmicb.2017.01765. PubMed DOI PMC

Armougom F., Henry M., Vialettes B., Raccah D., Raoult D. Monitoring bacterial community of human gut microbiota reveals an increase in Lactobacillus in obese patients and Methanogens in anorexic patients. PLoS ONE. 2009;4:e7125. doi: 10.1371/journal.pone.0007125. PubMed DOI PMC

Mack I., Cuntz U., Gramer C., Niedermaier S., Pohl C., Schwiertz A., Zimmermann K., Zipfel S., Enck P., Penders J. Weight gain in anorexia nervosa does not ameliorate the faecal microbiota, branched chain fatty acid profiles, and gastrointestinal complaints. Sci. Rep. 2016;6:26752. doi: 10.1038/srep26752. PubMed DOI PMC

Weiss G.A., Hennet T. Mechanisms and consequences of intestinal dysbiosis. Cell. Mol. Life Sci. 2017;74:2959–2977. doi: 10.1007/s00018-017-2509-x. PubMed DOI PMC

Macpherson A.J., Harris N.L. Interactions between commensal intestinal bacteria and the immune system. Nat. Rev. Immunol. 2004;4:478–485. doi: 10.1038/nri1373. PubMed DOI

Tlaskalova-Hogenova H., Stepankova R., Kozakova H., Hudcovic T., Vannucci L., Tuckova L., Rossmann P., Hrncir T., Kverka M., Zakostelska Z., et al. The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases. Cell. Mol. Immunol. 2011;8:110–120. doi: 10.1038/cmi.2010.67. PubMed DOI PMC

Seitz J., Belheouane M., Schulz N., Dempfle A., Baines J.F., Herpertz-Dahlmann B. The Impact of Starvation on the Microbiome and Gut-Brain Interaction in Anorexia Nervosa. Front. Endocrinol. (Lausanne) 2019;10:41. doi: 10.3389/fendo.2019.00041. PubMed DOI PMC

Wong J.M., de Souza R., Kendall C.W., Emam A., Jenkins D.J. Colonic health: fermentation and short chain fatty acids. J. Clin. Gastroenterol. 2006;40:235–243. doi: 10.1097/00004836-200603000-00015. PubMed DOI

Russell W.R., Gratz S.W., Duncan S.H., Holtrop G., Ince J., Scobbie L., Duncan G., Johnstone A.M., Lobley G.E., Wallace R.J., et al. High-protein, reduced-carbohydrate weight-loss diets promote metabolite profiles likely to be detrimental to colonic health. Am. J. Clin. Nutr. 2011;93:1062–1072. doi: 10.3945/ajcn.110.002188. PubMed DOI

Fernandes J., Su W., Rahat-Rozenbloom S., Wolever T.M., Comelli E.M. Adiposity, gut microbiota and faecal short chain fatty acids are linked in adult humans. Nutr. Diabetes. 2014;4:e121. doi: 10.1038/nutd.2014.23. PubMed DOI PMC

Turnbaugh P.J., Ley R.E., Mahowald M.A., Magrini V., Mardis E.R., Gordon J.I. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444:1027–1031. doi: 10.1038/nature05414. PubMed DOI

Morita C., Tsuji H., Hata T., Gondo M., Takakura S., Kawai K., Yoshihara K., Ogata K., Nomoto K., Miyazaki K., et al. Gut Dysbiosis in Patients with Anorexia Nervosa. PLoS ONE. 2015;10:e0145274. doi: 10.1371/journal.pone.0145274. PubMed DOI PMC

Lyte M. The microbial organ in the gut as a driver of homeostasis and disease. Med. Hypotheses. 2010;74:634–638. doi: 10.1016/j.mehy.2009.10.025. PubMed DOI

Gershon M.D., Tack J. The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology. 2007;132:397–414. doi: 10.1053/j.gastro.2006.11.002. PubMed DOI

Smits L.P., Bouter K.E., de Vos W.M., Borody T.J., Nieuwdorp M. Therapeutic potential of fecal microbiota transplantation. Gastroenterology. 2013;145:946–953. doi: 10.1053/j.gastro.2013.08.058. PubMed DOI

Kassam Z., Lee C.H., Yuan Y., Hunt R.H. Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Am. J. Gastroenterol. 2013;108:500–508. doi: 10.1038/ajg.2013.59. PubMed DOI

Borody T.J., Warren E.F., Leis S., Surace R., Ashman O. Treatment of ulcerative colitis using fecal bacteriotherapy. J. Clin. Gastroenterol. 2003;37:42–47. doi: 10.1097/00004836-200307000-00012. PubMed DOI

Cai T.T., Ye X.L., Yong H.J., Song B., Zheng X.L., Cui B.T., Zhang F.M., Lu Y.B., Miao H., Ding D.F. Fecal microbiota transplantation relieve painful diabetic neuropathy: A case report. Medicine (Baltimore) 2018;97:e13543. doi: 10.1097/MD.0000000000013543. PubMed DOI PMC

Kang D.W., Adams J.B., Coleman D.M., Pollard E.L., Maldonado J., McDonough-Means S., Caporaso J.G., Krajmalnik-Brown R. Long-term benefit of Microbiota Transfer Therapy on autism symptoms and gut microbiota. Sci. Rep. 2019;9:5821. doi: 10.1038/s41598-019-42183-0. PubMed DOI PMC

Alang N., Kelly C.R. Weight gain after fecal microbiota transplantation. Open Forum Infect. Dis. 2015;2:ofv004. doi: 10.1093/ofid/ofv004. PubMed DOI PMC

Gu L., Ding C., Tian H., Yang B., Zhang X., Hua Y., Zhu Y., Gong J., Zhu W., Li J., et al. Serial Frozen Fecal Microbiota Transplantation in the Treatment of Chronic Intestinal Pseudo-obstruction: A Preliminary Study. J. Neurogastroenterol Motil. 2017;23:289–297. doi: 10.5056/jnm16074. PubMed DOI PMC

Lahtinen P., Mattila E., Anttila V.J., Tillonen J., Teittinen M., Nevalainen P., Salminen S., Satokari R., Arkkila P. Faecal microbiota transplantation in patients with Clostridium difficile and significant comorbidities as well as in patients with new indications: A case series. World J. Gastroenterol. 2017;23:7174–7184. doi: 10.3748/wjg.v23.i39.7174. PubMed DOI PMC

Bures J., Cyrany J., Kohoutova D., Forstl M., Rejchrt S., Kvetina J., Vorisek V., Kopacova M. Small intestinal bacterial overgrowth syndrome. World J. Gastroenterol. 2010;16:2978–2990. doi: 10.3748/wjg.v16.i24.2978. PubMed DOI PMC

Polívková S., Vojtilová L., Husa P., Beneš J. Doporučený postup fekální bakterioterapie pro léčbu rekurentní klostridiové kolitidy. [(accessed on 1 August 2018)];2018 Available online: https://www.infekce.cz/DPFMT18.htm. (In Czech)

Hui W., Li T., Liu W., Zhou C., Gao F. Fecal microbiota transplantation for treatment of recurrent C. difficile infection: An updated randomized controlled trial meta-analysis. PLoS ONE. 2019;14:e0210016. doi: 10.1371/journal.pone.0210016. PubMed DOI PMC

Vetrovsky T., Baldrian P., Morais D., Berger B. SEED 2: a user-friendly platform for amplicon high-throughput sequencing data analyses. Bioinformatics. 2018;34:2292–2294. doi: 10.1093/bioinformatics/bty071. PubMed DOI PMC

Hammer O. Data analysis with PAST for micropaleontologists. Grzyb. Found. Spec. Pub. 2011;17:90.

Ghouri Y.A., Richards D.M., Rahimi E.F., Krill J.T., Jelinek K.A., DuPont A.W. Systematic review of randomized controlled trials of probiotics, prebiotics, and synbiotics in inflammatory bowel disease. Clin. Exp. Gastroenterol. 2014;7:473–487. doi: 10.2147/CEG.S27530. PubMed DOI PMC

Fukui H. Increased Intestinal Permeability and Decreased Barrier Function: Does It Really Influence the Risk of Inflammation? Inflamm. Intest. Dis. 2016;1:135–145. doi: 10.1159/000447252. PubMed DOI PMC

Sunkara T., Rawla P., Ofosu A., Gaduputi V. Fecal microbiota transplant - a new frontier in inflammatory bowel disease. J. Inflamm. Res. 2018;11:321–328. doi: 10.2147/JIR.S176190. PubMed DOI PMC

Belzer C., de Vos W.M. Microbes inside--from diversity to function: the case of Akkermansia. ISME J. 2012;6:1449–1458. doi: 10.1038/ismej.2012.6. PubMed DOI PMC

Million M., Angelakis E., Maraninchi M., Henry M., Giorgi R., Valero R., Vialettes B., Raoult D. Correlation between body mass index and gut concentrations of Lactobacillus reuteri, Bifidobacterium animalis, Methanobrevibacter smithii and Escherichia coli. Int. J. Obes. (Lond) 2013;37:1460–1466. doi: 10.1038/ijo.2013.20. PubMed DOI PMC

Ley R.E., Turnbaugh P.J., Klein S., Gordon J.I. Microbial ecology: human gut microbes associated with obesity. Nature. 2006;444:1022–1023. doi: 10.1038/4441022a. PubMed DOI

Larsen J.M. The immune response to Prevotella bacteria in chronic inflammatory disease. Immunology. 2017;151:363–374. doi: 10.1111/imm.12760. PubMed DOI PMC

Paramsothy S., Paramsothy R., Rubin D.T., Kamm M.A., Kaakoush N.O., Mitchell H.M., Castano-Rodriguez N. Faecal Microbiota Transplantation for Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. J. Crohns. Colitis. 2017;11:1180–1199. doi: 10.1093/ecco-jcc/jjx063. PubMed DOI

Louis P., Flint H.J. Formation of propionate and butyrate by the human colonic microbiota. Environ. Microbiol. 2017;19:29–41. doi: 10.1111/1462-2920.13589. PubMed DOI

Takahashi K., Nishida A., Fujimoto T., Fujii M., Shioya M., Imaeda H., Inatomi O., Bamba S., Sugimoto M., Andoh A. Reduced Abundance of Butyrate-Producing Bacteria Species in the Fecal Microbial Community in Crohn’s Disease. Digestion. 2016;93:59–65. doi: 10.1159/000441768. PubMed DOI

Sokol H., Leducq V., Aschard H., Pham H.P., Jegou S., Landman C., Cohen D., Liguori G., Bourrier A., Nion-Larmurier I., et al. Fungal microbiota dysbiosis in IBD. Gut. 2017;66:1039–1048. doi: 10.1136/gutjnl-2015-310746. PubMed DOI PMC

De Clercq N.C., Frissen M.N., Davids M., Groen A.K., Nieuwdorp M. Weight Gain after Fecal Microbiota Transplantation in a Patient with Recurrent Underweight following Clinical Recovery from Anorexia Nervosa. Psychother. Psychosom. 2019;88:58–60. doi: 10.1159/000495044. PubMed DOI

Yano J.M., Yu K., Donaldson G.P., Shastri G.G., Ann P., Ma L., Nagler C.R., Ismagilov R.F., Mazmanian S.K., Hsiao E.Y. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015;161:264–276. doi: 10.1016/j.cell.2015.02.047. PubMed DOI PMC

Sun W., Guo Y., Zhang S., Chen Z., Wu K., Liu Q., Liu K., Wen L., Wei Y., Wang B., et al. Fecal Microbiota Transplantation Can Alleviate Gastrointestinal Transit in Rats with High-Fat Diet-Induced Obesity via Regulation of Serotonin Biosynthesis. Biomed. Res. Int. 2018;2018:8308671. doi: 10.1155/2018/8308671. PubMed DOI PMC

Cao H., Liu X., An Y., Zhou G., Liu Y., Xu M., Dong W., Wang S., Yan F., Jiang K., et al. Dysbiosis contributes to chronic constipation development via regulation of serotonin transporter in the intestine. Sci. Rep. 2017;7:10322. doi: 10.1038/s41598-017-10835-8. PubMed DOI PMC

Mandic A.D., Woting A., Jaenicke T., Sander A., Sabrowski W., Rolle-Kampcyk U., von Bergen M., Blaut M. Clostridium ramosum regulates enterochromaffin cell development and serotonin release. Sci. Rep. 2019;9:1177. doi: 10.1038/s41598-018-38018-z. PubMed DOI PMC

Lloyd-Price J., Abu-Ali G., Huttenhower C. The healthy human microbiome. Genome Med. 2016;8:51. doi: 10.1186/s13073-016-0307-y. PubMed DOI PMC

Wilson B.C., Vatanen T., Cutfield W.S., O’Sullivan J.M. The Super-Donor Phenomenon in Fecal Microbiota Transplantation. Front. Cell. Infect. Microbiol. 2019;9:2. doi: 10.3389/fcimb.2019.00002. PubMed DOI PMC

Baskaran C., Misra M., Klibanski A. Effects of Anorexia Nervosa on the Endocrine System. Pediatr. Endocrinol Rev. 2017;14:302–311. doi: 10.17458/per.vol14.2017.BMK.effectsanorexianervosa. PubMed DOI

Ruusunen A., Rocks T., Jacka F., Loughman A. The gut microbiome in anorexia nervosa: relevance for nutritional rehabilitation. Psychopharmacology (Berl) 2019;236:1545–1558. doi: 10.1007/s00213-018-5159-2. PubMed DOI PMC

Metabolomic Study of Aging in fa/fa Rats: Multiplatform Urine and Serum Analysis

Altered Serum Immunological and Biochemical Parameters and Microbiota Composition in Patients With AN During Realimentation

Current Aspects of the Role of Autoantibodies Directed Against Appetite-Regulating Hormones and the Gut Microbiome in Eating Disorders

The intestinal microbiota and metabolites in patients with anorexia nervosa