Eva Budinska1, Jan Gojda2, Marie Heczkova3, Miriam Bratova3, Helena Dankova3, Petr Wohl3, Hana Bastova3, Vera Lanska3, Martin Kostovcik4, Milan Dastych5, Michal Senkyrik5, Jarmila Krizova6, Milos Mraz2, Jaromir Hradecky7,8, Jana Hajslova7, Martin Lenicek9, Kateřina Podzimkova10,11, Karel Chalupsky10,11, Radislav Sedlacek10,11, Monika Cahova3. 1. RECETOX, Faculty of Science Masaryk University, Brno, Czech Republic. 2. 2nd Department of Internal Medicine, Kralovske Vinohrady University Hospital and 3rd Faculty of Medicine, Charles University, Prague, Czech Republic. 3. Institute for Clinical and Experimental Medicine, Prague, Czech Republic. 4. BIOCEV, Institute of Microbiology, AS CR, Vestec, Czech Republic. 5. Department of Gastroenterology and Internal Medicine, University Hospital Brno, Brno, Czech Republic. 6. 3rd Department of Medicine, Department of Endocrinology and Metabolism, General University Hospital and 1st Faculty of Medicine, Charles University, Prague, Czech Republic. 7. University of Chemistry and Technology, Prague, Czech Republic. 8. Faculty of Forestry and Wood Sciences, Czech University of Life Sciences, Prague, Czech Republic. 9. Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University, Prague, Czech Republic. 10. Czech Centre for Phenogenomics, Vestec, Czech Republic. 11. Laboratory of Transgenic Diseases, Institute of Molecular Genetics CAS, Prague, Czech Republic.
Abstract
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.
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.
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