BACKGROUND: The gut microbiome and metabolome may significantly influence clinical outcomes in patients with short bowel syndrome (SBS). The study aimed to describe specific metagenomic/metabolomics profiles of different SBS types and to identify possible therapeutic targets. METHODS: Fecal microbiome (FM), volatile organic compounds (VOCs), and bile acid (BA) spectrum were analyzed in parenteral nutrition (PN)-dependent SBS I, SBS II, and PN-independent (non-PN) SBS patients. RESULTS: FM in SBS I, SBS II, and non-PN SBS shared characteristic features (depletion of beneficial anaerobes, high abundance of Lactobacilaceae and Enterobacteriaceae). SBS I patients were characterized by the abundance of oxygen-tolerant microrganisms and depletion of strict anaerobes. Non-PN SBS subjects showed markers of partial FM normalization. FM dysbiosis was translated into VOC and BA profiles characteristic for each SBS cohort. A typical signature of all SBS patients comprised high saturated aldehydes and medium-chain fatty acids and reduced short-chain fatty acid (SCFA) content. Particularly, SBS I and II exhibited low protein metabolism intermediate (indole, p-cresol) content despite the hypothetical presence of relevant metabolism pathways. Distinctive non-PN SBS marker was high phenol content. SBS patients' BA fecal spectrum was enriched by chenodeoxycholic and deoxycholic acids and depleted of lithocholic acid. CONCLUSIONS: Environmental conditions in SBS gut significantly affect FM composition and metabolic activity. The common feature of diverse SBS subjects is the altered VOC/BA profile and the lack of important products of microbial metabolism. Strategies oriented on the microbiome/metabolome reconstitution and targeted delivery of key compounds may represent a promising therapeutic strategy in SBS patients.

2nd Department of Internal Medicine Kralovske Vinohrady University Hospital and 3rd Faculty of Medicine Charles University Prague Czech Republic

3rd Department of Medicine Department of Endocrinology and Metabolism General University Hospital and 1st Faculty of Medicine Charles University Prague Czech Republic

BIOCEV Institute of Microbiology AS CR Vestec Czech Republic

Czech Centre for Phenogenomics Vestec Czech Republic

Department of Gastroenterology and Internal Medicine University Hospital Brno Brno Czech Republic

Faculty of Forestry and Wood Sciences Czech University of Life Sciences Prague Czech Republic

Institute for Clinical and Experimental Medicine Prague Czech Republic

Institute of Medical Biochemistry and Laboratory Diagnostics 1st Faculty of Medicine Charles University Prague Czech Republic

Laboratory of Transgenic Diseases Institute of Molecular Genetics CAS Prague Czech Republic

RECETOX Faculty of Science Masaryk University Brno Czech Republic

University of Chemistry and Technology Prague Czech Republic

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Pironi L, Arends J, Baxter J, et al. ESPEN endorsed recommendations. Definition and classification of intestinal failure in adults. Clin Nutr. 2015;34(2):171-180.

Jeppesen PB. Spectrum of short bowel syndrome in adults intestinal insufficiency to intestinal failure. J Parenter Enteral Nutr. 2014;38(1 Suppl):8S-13S.

Gillard L, Mayeur C, Robert V, et al. Microbiota is involved in post-resection adaptation in humans with short bowel syndrome. Front Physiol. 2017;8:224.

Mayeur C, Gratadoux JJ, Bridonneau C, et al. Faecal D/L Lactate ratio is a metabolic signature of microbiota imbalance in patients with short bowel syndrome. PLoS One. 2013;8(1):e54335.

De Preter V, Verbeke K. Metabolomics as a diagnostic tool in gastroenterology. World J Gastrointest Pharmacol Ther. 2013;4(4):97-107.

Pereira-Fantini PM, Byars SG, Pitt J, et al. Unravelling the metabolic impact of SBS-associated microbial dysbiosis: insights from the piglet short bowel syndrome model. Sci Rep. 2017;7:43326.

Janssen AW, Kersten S. Potential mediators linking gut bacteria to metabolic health: a critical view. J Physiol. 2017;595(2):477-487.

Koh A, De Vadder F, Kovatcheva-Datchary P, Backhed F. From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell. 2016;165(6):1332-1345.

Ridlon JM, Kang DJ, Hylemon PB. Bile salt biotransformations by human intestinal bacteria. J Lipid Res. 2006;47(2):241-259.

Ridlon JM, Kang DJ, Hylemon PB, Bajaj JS. Bile acids and the gut microbiome. Curr Opin Gastroenterol. 2014;30(3):332-338.

Caporaso JG, Kuczynski J, Stombaugh J, et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods. 2010;7(5):335-336.

Aitchison J. The Statistical Analysis of Compositional Data (Monographs on Statistics and Applied Probability). London: Chapman & Hall Ltd.; 1986.

R: A language and environment for statistical computing [computer program]. Version. Vienna, Austria: R Foundation for Statistical Computing.

Rohart F, Gautier B, Singh A, Le Cao KA. mixOmics: An R package for 'omics feature selection and multiple data integration. PLoS Comput Biol. 2017;13(11):e1005752.

Boccia S, Torre I, Santarpia L, et al. Intestinal microbiota in adult patients with short bowel syndrome: preliminary results from a pilot study. Clin Nutr. 2017;36(6):1707-1709.

Huang Y, Guo F, Li Y, Wang J, Li J. Fecal microbiota signatures of adult patients with different types of short bowel syndrome. J Gastroenterol Hepatol. 2017;32(12):1949-1957.

Joly F, Mayeur C, Bruneau A, et al. Drastic changes in fecal and mucosa-associated microbiota in adult patients with short bowel syndrome. Biochimie. 2010;92(7):753-761.

Walton C, Fowler DP, Turner C, et al. Analysis of volatile organic compounds of bacterial origin in chronic gastrointestinal diseases. Inflamm Bowel Dis. 2013;19(10):2069-2078.

Jalali M, Zare Sakhvidi MJ, Bahrami A, Berijani N, Mahjub H. Oxidative stress biomarkers in exhaled breath of workers exposed to crystalline silica dust by SPME-GC-MS. J Res Health Sci. 2016;16(3):153-161.

Orhan H, Van Holland B, Krab B, et al. Evaluation of a multi-parameter biomarker set for oxidative damage in man: increased urinary excretion of lipid, protein and DNA oxidation products after one hour of exercise. Free Radical Res. 2004;38(12):1269-1279.

Montanari C, Kamdem SLS, Serrazanetti DI, Vannini L, Guerzoni ME. Oxylipins generation in Lactobacillus helveticus in relation to unsaturated fatty acid supplementation. J Applied Microbiol. 2013;115(6):1388-1401.

Lee SM, Oh J, Hurh BS, Jeong GH, Shin YK, Kim YS. Volatile compounds produced by lactobacillus paracasei during oat fermentation. J Food Sci. 2016;81(12):C2915-C2922.

Bansal T, Alaniz RC, Wood TK, Jayaraman A. The bacterial signal indole increases epithelial-cell tight-junction resistance and attenuates indicators of inflammation. Proceedings of the National Academy of Sciences of the United States of America. 2010;107(1):228-233.

Korecka A, Dona A, Lahiri S, et al. Bidirectional communication between the Aryl hydrocarbon Receptor (AhR) and the microbiome tunes host metabolism. NPJ Biofilms Microbiomes. 2016;2:16014.

Zelante T, Iannitti RG, Cunha C, et al. Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity. 2013;39(2):372-385.

Zenewicz LA, Yin X, Wang G, et al. IL-22 deficiency alters colonic microbiota to be transmissible and colitogenic. J Immunol. 2013;190(10):5306-5312.

Behnsen J, Jellbauer S, Wong CP, et al. The cytokine IL-22 promotes pathogen colonization by suppressing related commensal bacteria. Immunity. 2014;40(2):262-273.

Bansal T, Englert D, Lee J, Hegde M, Wood TK, Jayaraman A. Differential effects of epinephrine, norepinephrine, and indole on Escherichia coli O157: H7 chemotaxis, colonization, and gene expression. Infect Immun. 2007;75(9):4597-4607.

Shimada Y, Kinoshita M, Harada K, et al. Commensal bacteria-dependent indole production enhances epithelial barrier function in the colon. PLoS One. 2013;8(11):e80604.

Thaiss CA, Zmora N, Levy M, Elinav E. The microbiome and innate immunity. Nature. 2016;535(7610):65-74.

Gao J, Xu K, Liu H, et al. Impact of the gut microbiota on intestinal immunity mediated by tryptophan metabolism. Front Cell Infect Microbiol. 2018;8:13.

Guilloteau P, Martin L, Eeckhaut V, Ducatelle R, Zabielski R, Van Immerseel F. From the gut to the peripheral tissues: the multiple effects of butyrate. Nutr Res Rev. 2010;23(2):366-384.

Soldavini J, Kaunitz JD. Pathobiology and potential therapeutic value of intestinal short-chain fatty acids in gut inflammation and obesity. Dig Dis Sci. 2013;58(10):2756-2766.

Ohkohchi N, Andoh T, Izumi U, Igarashi Y, Ohi R. Disorder of bile acid metabolism in children with short bowel syndrome. J Gastroenterol. 1997;32(4):472-479.

Pereira-Fantini PM, Lapthorne S, Joyce SA, et al. Altered FXR signalling is associated with bile acid dysmetabolism in short bowel syndrome-associated liver disease. J Hepatol. 2014;61(5):1115-1125.

Ward JBJ, Lajczak NK, Kelly OB, et al. Ursodeoxycholic acid and lithocholic acid exert anti-inflammatory actions in the colon. Am J Physio Gastrointest Liver Physiol. 2017;312(6):G550-G558.

Gojda J, Senkyrik, M, Tesinsky, P. Short bowel syndrome epidemiology, analysis from national HPN registry. Clin Nutr. 2017;36:S139-S140

Nightingale J, Woodward JM. Guidelines for management of patients with a short bowel. Gut. 2006;55(Suppl 4):iv1-12.

Determination of Butyrate Synthesis Capacity in Gut Microbiota: Quantification of but Gene Abundance by qPCR in Fecal Samples